Critical considerations in the administration of antineoplastic therapy for patients with malignant solid tumors undergoing hemodialysis.

Introduction

Patients with chronic kidney disease exhibit a higher risk of developing malignancies ( 1 ), and among those with end-stage renal disease (ESRD) on dialysis, approximately 7% are diagnosed with new-onset tumors within five years ( 2 , 3 ). However, patients with chronic kidney disease, particularly those with ESRD, are often excluded from clinical trials of antineoplastic agents. And this exclusion hinders the development of evidence-based treatment strategies and optimal, individualized chemotherapy dosing in this patient population ( 4 ).

Antineoplastic therapy in cancer patients with ESRD presents significant challenges. On one hand, these patients are at increased risk of developing extra-renal toxicity due to elevated systemic drug exposure; on the other hand, they may experience subtherapeutic drug concentrations as a result of premature and extensive drug elimination during dialysis. Unfortunately, there is little information on the appropriate dosing and pharmacokinetics of most chemotherapeutic agents in dialysis patients being treated for cancer. It is essential to propose an optimal anticancer drug strategy (dosage, timing, monitoring) to dialysis patients (whenever possible) rather than contraindicating it systematically. Therefore, dedicated pharmacokinetic studies in patients undergoing hemodialysis are warranted—particularly in those with cardiovascular or cerebrovascular comorbidities and in older adults. It is crucial to use the available data to adjust the dose of antineoplastic agents for these patients and to schedule the administration according to dialysis sessions. This article provides a comprehensive review of the impact of uremia and hemodialysis on the pharmacokinetics and metabolism of commonly used antineoplastic agents, supplemented by a synthesis of real-world evidence regarding their use in patients with end-stage renal disease undergoing hemodialysis. It aims to provide clinically valuable information to optimize antineoplastic therapy in this patient population, with the ultimate goal of prolonging survival periods and reducing the incidence of severe drug-related complications.

Epidemiology of patients with cancer undergoing hemodialysis

Higher incidence of malignancy in patients with uremia

It is estimated that by 2030, approximately 5.4 million people worldwide suffering from ESRD were undergoing some form of kidney replacement therapy, as reported by the CNRDS ( 5 ). Hemodialysis has been the predominant treatment modality for ESRD since 2012, accounting for 82.4% of incident ESRD cases in 2022 ( 6 ). The 5-year cumulative incidence of any cancer among 482,510 incident hemodialysis patients was 9.48%, with higher rates observed in specific subgroups, including older age, male, non-White individuals, non-Hispanic populations, those with a non-diabetic cause of end-stage renal disease (ESRD), recent initiation of hemodialysis therapy, a history of transplantation evaluation, those with acquired renal cystic disease, and an erythropoietin dose of 20,000 U/week or higher ( 7 , 8 ). A retrospective analysis of data from 1,377 incident hemodialysis patients across seven hemodialysis centers in Eastern Europe revealed that 63% had a history of cancer prior to hemodialysis initiation, predominantly hematologic and gastrointestinal malignancies; in contrast, 6.89% were diagnosed with de novo cancers after the initiation of hemodialysis, primarily involving gastrointestinal cancers, kidney cancer, urothelial cancers, lung cancer, and thyroid cancer ( 2 ). In recipients of renal transplants, the incidence of malignancies linked to infections and immune dysfunction—including Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, lip cancer, and non-epithelial skin cancers—was higher during periods of functional graft compared to periods of graft failure ( 9 , 10 ). The mean times for cancer development after the beginning of the dialysis sessions range from 1 to 5 years in different clinical research, with an even greater frequency observed within the first year ( 2 , 7 , 11 – 13 ). Another study investigating the risk of cancer recurrence among 4,912 dialysis patients with a history of neoplasia found that 323 (7%) experienced tumor recurrence, with a mean time to recurrence of 1.2 years from the initiation of dialysis; and 80% of these cases involved metastasis ( 3 ).

The carcinogenic factors associated with uremia and hemodialysis therapy primarily include impaired immune function ( 7 , 14 ), oxidative stress and reduced antioxidant capacity ( 15 ), inadequate dialysis efficacy, accumulation of carcinogenic substances resulting from uremic toxins and the biological incompatibility of dialysis membranes, leaching of plasticizers from tubing materials ( 16 ), chronic microinflammation ( 17 ), and exposure to medications with potential carcinogenic risks ( 18 – 20 ). Furthermore, acquired renal cystic disease significantly increases the risk of developing renal cell carcinoma ( 18 ). The carcinogenesis factors triggered by uremia and hemodialysis treatment were listed in Table 1 ( 7 , 14 – 20 ).

Survival rate in dialysis patients with malignancy

Cancer was an independent predictor of elevated mortality risk among hemodialysis patients, with those diagnosed facing a sixfold greater risk compared to their cancer-free counterparts ( 2 ). In a large registry-based study from Australia and New Zealand, the standardized mortality rate (SMR), which is a measure of excess deaths in dialysis patients relative to the general population, was 2.6 for all cancers and 1.3 for de novo cancer, particularly kidney, colorectal, and lung cancers ( 21 ). Patients with recurrent cancers exhibited a 3-year survival rate of less than 50%, and the most common recurrent cancers included lymphoma, tumors of the urinary tract, lung cancer, and melanoma ( 22 ). A retrospective cohort study of 639 patients initiating hemodialysis between July 1999 and December 2017 demonstrated that the 1-, 5-, and 10-year cumulative survival rates following cancer diagnosis were 58.73%, 34.64%, and 20.41%, respectively ( 8 ). A retrospective study of 675 hemodialysis patients diagnosed with cancer revealed that effective chemotherapy could offer the potential for prolonged survival, even in cases of unresectable tumors ( 23 ).

Therefore, early screening and evidence-based optimization of antineoplastic treatment regimens are critical to improving both overall survival and quality of life in hemodialysis patients with concomitant malignancies.

The impact of malignant tumors and antineoplastic therapy on patients undergoing hemodialysis

Electrolyte and acid-base imbalance

Patients with cancer are especially susceptible to severe electrolyte disturbances resulting from paraneoplastic syndromes, surgical removal of endocrine organs, inadequate nutritional intake, tumor metastases, and concomitant chemotherapy agents such as platinum and ifosfamide ( 24 ), immune checkpoint inhibitors (ICIs), epidermal growth factor receptor inhibitors, and fibroblast growth factor inhibitors ( 25 ). Hyponatremia ( 26 ), hypocalcemia ( 27 ), hypokalemia, hypomagnesemia, hypercalcemia ( 28 ), and, less commonly, lactic acidosis ( 29 ) are frequently observed electrolyte disturbances that may occur in cancer patients. Notably, in ESRD patients undergoing hemodialysis, the common electrolyte abnormalities include fluid overload, hyperkalemia, hyperphosphatemia, and metabolic acidosis. Additionally, tumor lysis syndrome is unique to cancer patients and can be associated with acute kidney injury, acute uric acid nephropathy and multiple electrolytes disturbances, including hyperkalemia, hyperphosphatemia, hypocalcemia and hypermagnesemia.

Therefore, electrolyte disturbances and metabolic acidosis should be closely monitored in hemodialysis patients with malignancy, particularly those receiving antineoplastic agents that may aggravate such disturbances.

Malnutrition and infection

Patients with advanced malignancies often suffer from malnutrition and infections, which contribute to reduced tolerance to chemotherapy, a condition further exacerbated by ESRD. Moreover, hypoproteinemia affects the binding and metabolism of chemotherapy drugs. Besides, malnutrition, the administration of chemotherapy drugs, and gastrointestinal bleeding all exacerbate the condition of anemia in cancer patients undergoing hemodialysis.

High incidence of cardiovascular events

Cancer-associated hypertension—including paraneoplastic syndromes driven by excessive vasoactive peptide secretion ( 30 ), certain antineoplastic agents ( 31 , 32 ), and nonsteroidal anti-inflammatory drugs—is associated with an elevated risk of major adverse cardiovascular events, including myocardial ischemia, heart failure, stroke, and cardiovascular death. Cancer-associated thrombotic microangiopathy—driven by mucin-producing malignancies ( 33 ) and select chemotherapeutic agents ( 34 )—mediates microvascular endothelial injury, thereby triggering platelet activation, fostering microthrombus formation, amplifying blood pressure lability, and worsening anemia; these interrelated pathophysiological processes collectively accelerate cardiovascular event development. Furthermore, Certain antineoplastic agents exhibit cardiotoxic properties. These factors contribute to an increased incidence of cardiovascular events in patients with ESRD.

Moreover, opioid prescribing for patients with malignancy undergoing hemodialysis must account for uremic physiology as well as the degree of renal excretion and drug clearance achieved during hemodialysis sessions ( 35 ). The potential cardiovascular adverse effects and the risk of febrile neutropenia should be closely monitored in older patients with ESRD receiving antineoplastic therapy ( 36 ). The impact of malignant tumors and anti-tumor treatments on hemodialysis patients is shown in the Figure 1 .

The influence of uremic and hemodialysis on drug metabolism

The increased volume of distribution of drugs in hemodialysis patients

Chemotherapeutic drugs that exhibit a high volume of distribution are generally less accessible to dialysis compared to those with a low volume of distribution, as the latter are more likely to be restricted to the intravascular space ( 37 ). This abnormality may be due to fluid overload, decreased protein binding, or altered tissue binding.

The influence of drug metabolites and molecular weight on dialysis clearance

Drugs with a molecular weight less than 1kDa can diffuse through membranes. However, drugs that primarily bind to plasma proteins are poorly amenable to dialysis due to the high molecular weight and structural characteristics of the drug-protein complex ( 37 ). Acidic medications generally exhibit binding affinity toward albumin. Consequently, in patients with severe renal impairment, reduced plasma protein levels may increase the concentration of unbound drug, thereby enhancing its elimination. Basic drugs exhibit a high affinity for alpha1-acid glycoprotein. Given the elevated levels of this acute-phase reactant in hemodialysis patients—where it is predominantly bound to basic substances—the administration of cationic drugs may result in increased free drug concentrations, leading to enhanced pharmacological effects and an increased risk of dose-dependent adverse events ( 38 ). Moreover, elimination through dialysis is also influenced by the transfer rate of the drug from tissues to plasma; specifically, a shorter plasma half-life facilitates a higher transfer rate, thereby enhancing the dialyzability of the drug. FHD has been recommended as an indicator associated with drug dialyzability; when FHD exceeds 25%, the drug should be administered after dialysis ( 39 ).

Notably, another factor concerns the transformation of drugs into active or inactive metabolites that may have different pharmacokinetic characteristics compared with the parent drug.

Abnormal liver metabolism

Chemotherapeutic drugs mainly metabolized in the liver via CYP3A4, CYP2D6, or cytochrome P450 enzymes in the liver. For patients with concomitant liver injury or those with underlying hepatic conditions such as liver cancer and cirrhosis—both of which are associated with reduced hepatic reserve—special attention should be paid to the impact of impaired liver function on drug metabolism.

Hence, a customized strategy for each medication, informed by their pharmacokinetic profiles in hemodialysis patients, is crucial for optimizing patient outcomes while minimizing potential risks in this susceptible population.

The administration of antineoplastic agent in hemodialysis patients

Antitumor drugs are primarily categorized into three main classes: traditional cytotoxic chemotherapeutic agents, targeted chemotherapeutic agents, and immunotherapies for tumor treatment. The summary of antineoplastic agents in hemodialysis patients is presented in Table 2 .

Traditional cytotoxic chemotherapeutic agents

Platinum antineoplastic agents

Carboplatin, cisplatin and oxaliplatin are mainly renal excretion and dialyzable through hemodialysis. Hemodialysis can eliminate platinum antineoplastic agents contributing to its utility as a treatment modality for platinum drug overdose.

Carboplatin is recommended to be based only on pharmacokinetics yet not calculated in relation to body surface. In patients undergoing hemodialysis, the dose that can be safely administered is the area under the concentration-time curve (AUC) 3.5–5 mg/ml·min ( 40 ). Another case report suggests that higher doses of carboplatin, administered with a shorter interval between the end of infusion and the initiation of hemodialysis (1 to 2 hours), may also be feasible in the therapy of ovarian cancer ( 23 , 41 , 42 ). Cisplatin-based chemotherapy can be administered to patients with advanced ovarian germ cell tumors and renal insufficiency at reduced doses (50–75% of the standard dose) to minimize adverse effects while maintaining efficacy within a multidisciplinary treatment framework ( 23 , 43 – 45 ). Oxaliplatin is recommended to be administered at a reduced dose of 25%–50% after dialysis, with the dosing interval extended to three weeks ( 23 , 46 ). Notably, hypomagnesemia, hyponatremia, and Fanconi syndrome should be closely monitored in hemodialysis patients with residual renal function who are receiving platinum-based antineoplastic therapy ( 47 ). In addition, targeted delivery of platinum-based antineoplastic agents may reduce the incidence of adverse effects. TPNPs are a promising antitumor agent as a self-assembled nanoprodrug with high drug loading capacity. As a cisplatin and tolfenamic acid-based prodrug, these self-assembled nanoparticles have been shown to improve therapeutic efficacy in a human ovarian cancer xenograft mouse model while reducing systemic toxicity ( 48 ).

Irinotecan

Irinotecan is converted to an active metabolite, SN-38 and urinary excretion accounts for <20% of the elimination of the administered dose. Pharmacokinetic evaluation demonstrated that patients with severe chronic kidney disease exhibited higher unbound levels of SN-38 relative to individuals with normal renal function, primarily due to the suppression of SN-38 protein binding by the uremic toxin 3-carboxy-4-methyl-5-propyl-2-furanpropanoate ( 49 ). A noncompartmental pharmacokinetic analysis indicates that irinotecan exhibits partial dialyzability, whereas SN-38 appears to be nondialyzable ( 50 ).Thus, a lower weekly dose of 50 mg/m² of irinotecan may be more suitable to minimize the risk of severe neutropenia and infections, ideally administered following hemodialysis or on days without dialysis ( 23 , 50 ). UGT1A polymorphisms, including variant alleles of UGT1A1*28, UGT1A1*60 and UGT1A9*22, may lead to accumulation of SN-38 in patients with ESRD, which may result in the lethally neutropenia ( 51 ).

Etoposide

Approximately 40% of etoposide dose is excreted by the kidneys. Etoposide is not removed by hemodialysis and it can be used before or after hemodialysis sessions ( 43 ). Research has shown increased AUC and extended half-life of etoposide in patients, leading to recommendations for a 50%–60% dose reduction prior to hemodialysis to mitigate the risk of hematological toxicity ( 52 ). A dose-escalation trial involving five patients received etoposide at an initial dose of 50 mg/m² in combination with cisplatin prior to hemodialysis, demonstrating manageable adverse effects ( 53 ).

5-FU and 5-FU-related chemotherapeutic drug

5-fluorouracil

5-fluorouracil (5-FU) and its metabolite, fluorodeoxyuridine monophosphate, inhibits explicitly thymidylate synthase, which is crucial for synthesizing the thymidine necessary for DNA replication. 5-FU, a molecular entity weighing 130 Da, is mainly catabolized in the liver and a mere 15% via the urine in its original form. During hemodialysis session, around 90% of 5-FU and its metabolites-α-fluoro-β-alanine (FBAL) were directly cleared from the blood ( 54 ). 5-FU has been successfully used in hemodialysis patients with advanced hepatocellular carcinoma, esophageal cancer, and colon carcinoma ( 23 , 55 ). Nevertheless, cases of lactic acidosis and hyperammonemia associated with 5-fluorouracil have been observed in cancer patients, and hemodialysis has proven to be an effective therapeutic intervention ( 56 , 57 ). Myelosuppression is frequently observed, which can lead to reduced blood cell counts and increased risks of infection, anemia, and bleeding.

Capecitabine

Capecitabine, with a molecular weight of 359.3 Da, is a prodrug of 5-fluorouracil (5-FU), which is metabolized in the liver to 5’-deoxy-5-fluorocytidine and subsequently to 5’-deoxy-5-fluorouridine (5’-DFUR), then converted to the active metabolite 5-FU within tumor tissues. This prodrug is processed and excreted mainly through renal pathways, with 96% of its dosage identifiable in the urine. Pharmacokinetics study demonstrated that administration of capecitabine is contraindicated in patients with a GFR below 30 mL/min, as a phase II study demonstrated a higher frequency of grade 3 and 4 adverse events in this population ( 58 , 59 ). However, case reports of capecitabine support a recommended dose reduction of 50% to 75% in patients undergoing hemodialysis, which has demonstrated both good tolerability and efficacy in individuals with malignancies on hemodialysis ( 58 , 60 ). Myelosuppression and cardiotoxicity necessitate careful dose management and vigilant medical supervision.

Gemcitabine (2’,2’-difluorodeoxycytidine)

The primary metabolite of gemcitabine, difluorodeoxyuridine (dFdU), which is non-cytotoxic, exhibits an extended half-life and remains detectable in plasma for multiple days, even following minimal doses of the drug ( 61 ). The renal elimination of gemcitabine and its metabolites contribute <10% and 90%, respectively, to their complete removal. Pharmacokinetic parameters of gemcitabine were not altered, but a five-to tenfold prolongation of terminal half-life as well as a higher AUC of dFdU were found in a patient on hemodialysis ( 62 ). Given that hemodialysis is effective in lowering plasma levels of dFdU, it is recommended to start the procedure within 6 to 12 hours following gemcitabine administration ( 23 , 63 ). A case report demonstrated the efficacy and safety of combination chemotherapy with full-dose gemcitabine (1,000 mg/m²) and reduced-dose cisplatin (35 mg/m²) in a patient with ESRD who had metastatic renal allograft collecting duct carcinoma (CDC) ( 64 ). Due to the heightened risk of severe adverse drug reactions (ADRs) in individuals with dihydropyrimidine dehydrogenase deficiency (DPYD)—a genetic variant that impairs fluoropyrimidine metabolism—screening for dihydropyrimidine dehydrogenase (DPD) deficiency prior to treatment is advised before starting fluoropyrimidine-based chemotherapy ( 65 ). Phenotypic assessment using the plasma [UH2]:[U] ratio is advised for patients with ESRD ( 66 ).

Vinorelbine

Vinorelbine is mainly eliminated through the liver, with only 8% of the administered dose recovered unchanged from the urine. A 30% to 50% dose reduction of vinorelbine has been shown to be effective and well-tolerated in hemodialysis patients with Hodgkin lymphoma or metastatic breast cancer, helping to prevent adverse effects such as myelosuppression ( 67 ).

Paclitaxel and docetaxel

The renal removal of paclitaxel and docetaxel is insignificant. Both drugs strongly bind to proteins such as albumin and alpha-1-glycoprotein, and not dialysable. Case reports indicate that paclitaxel doses ranging from 75 to 150 mg/m²—and in some instances exceeding this range—were administered safely to 16 patients with ovarian cancer undergoing maintenance hemodialysis, without necessitating dose modification attributable to renal impairment ( 23 , 40 , 43 , 68 , 69 ). A reduced dose of 65 mg/m² of docetaxel is recommended for cancer patients undergoing hemodialysis ( 23 , 43 , 44 , 70 ). The common side-effect of paclitaxel is peripheral neuropathy, neutropenia, and hypersensitivity reactions. Notably, paclitaxel-coated balloons (AcoArt Orchid) have demonstrated both efficacy and safety in the treatment of dysfunctional arteriovenous fistulas in hemodialysis patients ( 71 ).

Actinomycin D

About 30% of actinomycin D is excreted via urine and a standard dose can be given with precaution in patients with ESRD. It is not dialysable; hence, it can be given before or after dialysis. The primary concern associated with administering actinomycin D to patients undergoing hemodialysis is its propensity to induce myelosuppression; therefore, a 20–30% dose reduction is recommended—based on evidence from case report in end-stage renal disease ( 72 ).

Doxorubicin and epirubicin

Doxorubicin and epirubicin are removed mainly by the liver and, to a lesser degree, are excreted by the kidneys (15% and 10%, respectively). Case reports documented patients with early-stage breast cancer undergoing hemodialysis who received epirubicin well, without severe adverse reactions ( 44 , 73 ). However, pharmacokinetic studies showed that the AUC of doxorubicin and its active metabolite doxorubicinol was approximately 1.5-fold and 3-fold higher, respectively, in patients undergoing hemodialysis compared to those with normal renal function, with a similar elevation in AUC also observed for epirubicin ( 74 ). Doxorubicin administered at a reduced dose of 65 mg/m² was well tolerated in patients undergoing hemodialysis, despite concurrent leukopenia and thrombocytopenia ( 23 , 43 , 75 ).Therefore, acute myelosuppression and cumulative dose-related cardiotoxicity should be routinely monitored in hemodialysis patients receiving doxorubicin or epirubicin, as such monitoring forms the basis for dose adjustment. Doxorubicin bound to albumin through self-assembling dyes acting as Specific Polymolecular Ligands represents a promising immunotargeted therapy that may reduce adverse effects while enhancing doxorubicin accumulation in tumor tissue ( 76 ).

Cyclophosphamide and ifosfamide

Cyclophosphamide (CTX) is inactive until processed by the liver into a number of active metabolites, which are eliminated through the kidneys. Approximately 50% to 70% of CTX is excreted by kidneys within 48 hours, with approximately 32% expelled in its unchanged form. The AUC was increased in hemodialysis patients and it is necessary to reduce the dose of CTX by 25-30% in hemodialysis patients. Approximately 22% of the drug was removed during the first three hours of dialysis, with an average total clearance rate lower compared to individuals with normal kidney function ( 70 , 77 ). Therefore, a 25–30% dose reduction of CTX is recommended in patients undergoing hemodialysis ( 44 , 78 ). Ifosfamide is mainly processed in the liver. The prodrug is converted into the active metabolite phosphoramide mustard, but it also produces the urotoxic compound acrolein as well as the neurotoxic and nephrotoxic metabolite chloracetaldehyde. In vitro studies suggest that hemodialysis can decrease ifosfamide concentrations by 87% and chloracetaldehyde by 77%. Three hemodialysis patients received individually adjusted doses of ifosfamide (initial dose: 1.5 -2g/m²), with myelosuppression identified as the most frequent adverse event and no instances of life-threatening toxicity observed ( 78 , 79 ). Notably, both CTX and ifosfamide are associated with increased bladder toxicity, thereby elevating the risk of urinary system malignancies ( 80 ).

Targeted chemotherapeutic agents

Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors)

PARP inhibitors trap DNA to destabilize the replication fork and induce cell death through mitotic catastrophe caused by replication stress, which are used to treat BRCA-mutated ovarian cancer, breast cancer, pancreatic cancer. Olaparib’s prototype is excreted in urine by 15%, and its metabolites are excreted in urine. Olaparib was not detectable in the dialysate samples. Pharmacokinetic studies have shown that patients with renal impairment exhibit increased systemic exposure and higher peak concentrations of the PARP inhibitor olaparib, which may progressively increase the risk of hematologic adverse effects ( 81 ). A daily dose of 400 mg olaparib, given in two divided doses, was well tolerated by a patient with ESRD receiving hemodialysis, resulting in 16 months of progression-free survival ( 82 ).

Anti-angiogenics agents

Monoclonal antibodies are eliminated via catabolism by lysosomal degradation to peptides and amino acids. The high molecular weight of monoclonal antibodies makes it impossible for the kidneys to eliminate them, unless there is a presence of pathologic conditions. And it is not dialyzable. However, the blocking of Vascular endothelial growth factor/Vascular endothelial growth factor receptors pathway may induce hypertension and TMA in ESRD patients. The pharmacokinetic parameters of Bevacizumab observed in a patient receiving this dosage were comparable to those reported in individuals with normal renal function who were administered 10 mg/kg every 14 days ( 83 ). Bevacizumab has been also used at a dose of 5 mg/kg every 14 days in hemodialysis patients ( 84 , 85 ). Sorafenib, Axitinib, Sunitinib, Ramucirumab, Pazopanib are metabolized mainly in the liver and their urinary excretion less than 20%. Pharmacokinetic and clinical assessments have shown that these treatments are effective and well-tolerated in hemodialysis patients with cancer ( 23 , 84 – 88 ).

Cabozantinib and its metabolites are excreted in the feces (54%), as well as in the urine (27%). Cabozantinib displays a long-term plasma half-life (-120 h) and accumulates five-fold by day 15 following daily dosing based on AUC. Its AUC was increased by 7–30% in subjects with mild/moderate renal impairment ( 89 ). Therefore, the frequency of Cabozantinib use should be reduced in hemodialysis patients. Case report observed that a patient tolerated a regorafenib dose of 40 mg daily for 21 days, the treatment was interrupted after one cycle of treatment because of a septic shock and the worsening of cardiomyopathy ( 90 ).

As far as nintedanib, less than 1% is excreted via the kidney and adjustment dose in patients with mild to moderate renal injury is not required. However, Lenvatinib has been associated with a range of renal adverse effects, such as hypertension, focal segmental glomerulosclerosis, and TMA ( 91 ). Vandetanib has been found to inhibit certain human renal transporters, resulting in reduced creatinine clearance and enhanced cisplatin-induced nephrotoxicity ( 92 ). Therefore, Lenvatinib and Vandetanib should be avoid in patients with residual renal function. Collectively, multicenter retrospective study indicated that anti-angiogenics agents seem to be effective and can be used among patients undergoing hemodialysis. PK assessments were not modified in patients undergoing hemodialysis compared with a population not undergoing dialysis ( 84 , 93 , 94 ).

Epidermal growth factor receptor tyrosine kinases inhibitor (EGFR-TKIs)

EGFR-TKIs are poorly removed by hemodialysis, as over 90% of EGFR-TKIs bind to plasma proteins; these agents are primarily metabolized in the liver and predominantly excreted via bile. Available EGFR inhibitors presently include three monoclonal antibodies (cetuximab, panitumumab and necitumumab) and five small molecule tyrosine kinase inhibitors (TKIs – gefitinib, erlotinib, afatinib, dacomitinib and osimertinib). Cetuximab, panitumumab, gefitinib, and erlotinib have been found to be well-tolerated in patients with ESRD or those undergoing hemodialysis, with no requirement for dose adjustments ( 23 , 95 ). Three patients with lung cancer undergoing hemodialysis achieved a partial response when treated with afatinib, with no serious adverse events observed, and pharmacokinetic data were consistent with those seen in individuals with normal renal function ( 96 ). A multicenter retrospective analysis of 18 patients with EGFR-mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs)—including gefitinib, erlotinib, and afatinib—across 22 institutions in Japan reported an objective response rate of 44.4% and a median overall survival of 38.6 months. Dose adjustments were required in five patients (27.8%). Treatment discontinuation due to any cause or specifically attributable to treatment-related adverse events (TRAEs) occurred in 50.0% and 33.3% of patients, respectively. The most frequently reported grade 3 or higher adverse events were neutropenia, thrombocytopenia, anemia, and febrile neutropenia, all of which were controllable with appropriate management ( 43 ).

Breakpoint cluster region-Abelson leukemia virus inhibitors

Imatinib is the only approved and widely used breakpoint cluster region-Abelson leukemia (BCR-ABL) inhibitor in clinical practice for gastrointestinal stromal tumors. Following mainly hepatic metabolization via CYP3A4 or CYP3A5, Imatinib mesylate and its metabolites are eliminated mostly in feces due to hepatobiliary excretion, with 13% of excretion in the urine. Pharmacokinetic evaluation in a patient with ESRD undergoing hemodialysis and receiving oral imatinib at a daily dose of 400 mg revealed that hemodialysis had no clinically significant effect on systemic imatinib exposure ( 23 , 97 , 98 ).

Mammalian target of rapamycin inhibitors

Everolimus and Temsirolimus are both extensively metabolized by the liver via CYP3A4 and only less excreted in the urine. A PK study showed no significant differences in PK parameters of temsirolimus between patients undergoing hemodialysis and those without dialysis ( 99 ). Everolimus and temsirolimus, indeed, are not dialyzed by commonly used membranes. Case reports and a retrospective analysis involving 11 patients with metastatic renal cell carcinoma and end-stage renal disease on hemodialysis indicated that everolimus therapy is feasible, demonstrating favorable efficacy and no unforeseen adverse effects ( 23 , 43 , 100 ). Ten Japanese patients with metastatic renal cell carcinoma undergoing hemodialysis were treated with temsirolimus, achieving favorable clinical outcomes without unexpected severe adverse events and sustaining a relative dose intensity of 89.5% over the entire study duration ( 101 ).

Human epidermal growth factor receptor-monoclonal antibodies

These agents are represented either by monoclonal antibodies (trastuzumab, pertuzumab, Trastuzumab Emtansine – T-DM1) or by TKIs (lapatinib and neratinib). As a recombinant humanized monoclonal antibody, the elimination of Trastuzumab involves clearance of immunoglobulin G through the reticuloendothelial system. Trastuzumab emtasine (T-DM1) elimination half-life (approximately 4 days) is shorter than that for a typical IgG1 antibody (i.e. 2–3 weeks); And due to its high molecular weight, clearance of the drug is not expected to be significantly influenced by renal function ( 102 ). No increased toxicity and favorable clinical outcomes have been observed with both trastuzumab and T-DM1 in breast cancer patients undergoing hemodialysis ( 23 , 103 ). Lapatinib is primarily excreted in the feces, less than 2% of administered oral dose being excreted in the urine. Lapatinib demonstrated efficacy in a breast cancer patient receiving hemodialysis for more than three years, with no substantial increase in toxicity ( 104 ).

B-Raf proto-oncogene, serine/threonine kinase inhibitors

Renal excretion of dabrafenib is higher than that of vemurafenib (23% urinary excretion versus 1%) and the risk of accumulation in patients with severe CKD or ESRD is higher, therefore, dabrafenib should be used with greater caution in the setting of renal failure. Vemurafenib, due to prolonged QTc interval, and the combination of dabrafenib with trametinib were administered with dose reductions in patients with ESRD ( 105 – 107 ).

Cyclin-dependent kinase 4/6 inhibitor

More recently, Cyclin-dependent kinase 4/6 (CKD 4/6) inhibitor drugs such as (palbociclib, ribociclib, and abemaciclib) have been introduced for hormone receptor-positive metastatic breast cancers, which enhance the efficacy of antiestrogen drugs. All the CKD 4/6 inhibitors are protein-bound molecules metabolized in the liver by cytochrome P450 isoenzymes and less renal excretion. In patients with severe renal impairment, systemic exposure—as measured by AUC inf —was 31% higher, and peak plasma concentration (C max ) was 15% greater, relative to individuals with normal renal function ( 108 ). Furthermore, under steady-state conditions, both the 24-hour area under the concentration–time curve (AUC inf ) and C max were elevated in hemodialysis-dependent patients receiving a reduced palbociclib starting dose of 100 mg/day, compared with values observed in participants with preserved renal function who received 125 mg/day in a Phase I clinical trial ( 109 ). Therefore, dose reduction of palbociclib is recommended for patients undergoing maintenance hemodialysis.

Selective estrogen receptor modulator

Tamoxifen and Anastrozole are mainly excreted in feces and only 9%-14% in the urine. The plasma concentrations of the two drugs were similar in hemodialysis patients compared to non-hemodialysis patients. Exemestane, letrozole, and fulvestrant all had only a small portion excreted unaltered in the urine. Thus, dose adjustments are not required for the use of selective estrogen receptor modulators in patients undergoing hemodialysis ( 23 , 110 , 111 ). Megestrol acetate has demonstrated safety and efficacy in the treatment of metastatic breast cancer and has been shown to improve nutritional status and attenuate systemic inflammation in elderly hemodialysis patients with cachexia ( 112 ).

Immunotherapies for malignancies

Immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) are humanized or fully human immunoglobulin antibodies. Their elimination occurs primarily via intracellular catabolism through lysosomal degradation following pinocytosis, particularly in organs and tissues enriched with endothelial cells, or via receptor-mediated endocytosis ( 113 ). The half-lives of these agents range from 6 to 27 days ( 114 ). Pharmacokinetic analysis in patients stratified by estimated glomerular filtration rate (eGFR)—including mild (eGFR: 60–89 mL/min/1.73 m²; n=313), moderate (eGFR: 30–59 mL/min/1.73 m²; n=140), and severe (eGFR: 15–29.89 mL/min/1.73 m²; n=3) renal impairment—revealed no clinically significant differences in nivolumab clearance between patients with renal impairment and those with normal renal function. Therefore, dose adjustment is not recommended in patients with renal impairment ( 115 ). Pharmacokinetic analyses further indicated the absence of dialytic clearance ( 114 ). Case series report a variety of malignancies treated with different ICIs in ESRD, including melanoma, renal cell carcinoma, Colorectal cancer, RCC, renal cell cancer; NSCLC, non-small cell lung cancer ( 116 ). A review of 14 articles on the use of immune checkpoint inhibitors (ICIs) in cancer patients undergoing dialysis encompassed 54 reported cases. Among these patients, 46% (25 individuals) achieved at least a partial response, whereas 35% (19 individuals) experienced disease progression. Immune-related adverse events (irAEs) were observed in 27 individuals (50%), with 75% of these cases classified as grade 1 or 2. Treatment involving corticosteroids was required in 18.5% of patients ( 117 ).Another analysis based on 33 articles included 98 cases, of which 80 patients had been diagnosed with ESKD prior to receiving ICIs, while an additional 18 were kidney transplant recipients who experienced allograft rejection following ICI administration and subsequently initiated dialysis while continuing treatment with these agents ( 116 ). Overall, 49% of the patients (48 out of 98) developed irAEs. Among these individuals, 15 patients (15%) experienced grade 3 or grade 4 adverse events, including encephalitis and myocarditis, as well as pemphigoid rash. These severe immune-related complications are comparable to those observed in the general population and occur infrequently, with reported incidence rates of 1.3% and less than 1%, respectively ( 118 ). Thus, the efficacy and safety profiles of ICIs are comparable between dialysis and non-dialysis patients. Administration of ICIs in patients undergoing dialysis does not lead to a higher risk of developing irAEs ( 119 ). However, relatively high frequency of hematologic adverse events was observed in patients with ESKD receiving ICI therapy, which may be related with uremic accumulation and dialysis incompatibility ( 120 ). Corticosteroids are recommended as the first-line treatment for ESRD patients experiencing severe irAEs ( 121 , 122 ).

Chimeric antigen receptor T cell therapy

Chimeric antigen receptor T cell (CAR-T) therapy is a form of adoptive immunotherapy that involves the ex vivo genetic modification of a patient’s T cells to express chimeric antigen receptors specifically directed against tumor-associated antigens. This modification enables the engineered T cells to selectively recognize and target malignant cells. After in vitro expansion, these modified T cells are reinfused into the patient, where they induce targeted immune activation and mediate the elimination of tumor cells ( 123 ). This therapy has shown remarkable efficacy in treating hematological malignancies such as lymphoma, leukemia, and multiple myeloma, as well as some solid tumors ( 124 ). During the CAR T therapy, lymphodepletion is important to allow for proper expansion and survival of CAR T-cell products. Fludarabine and cyclophosphamide are the most common lymphodepleting agents. Fludarabine’s major metabolite, 2-F-ara-A, is primarily excreted in the urine. And approximately 50% to 70% of CTX is excreted by kidneys as mentioned above. Therefore, dose adjudgment is vital for the ESRD patients receiving the lymphodepletion.

lymphodepletion regimen for tisa-cel or brexu-cel is suggested using dose-reduce fludarabine by 50% to 12.5–15 mg/m 2 with cyclophosphamide maintained at full dose (500 mg/m 2 ); and with hemodialysis performed on day 5 and day 3, approximately 12 hours following chemotherapy ( 125 ). Hunter et al. recently published their experience with CAR T-cell therapy in two ESRD patients with R/R DLBCL. Their lymphodepletion strategy was elected to dose-reduce cyclophosphamide 40% to 300 mg/m 2 in their axi-cel patient while maintaining the standard cyclophosphamide dose (300 mg/m 2 ) in their liso-cel patient. And the hemodialysis was performed 12 hours after each dose that was given. The adverse effects of CAR T-cell therapy should be monitored in ESRD patients, including cytokine release syndrome, immune effector-associated neurotoxicity syndrome and tumor lysis syndrome ( 126 ).

Plasmapheresis or hemofiltration helped quickly clear cytokines, speeded up patient recover, and successfully resolved the severe cytokine release syndrome crisis. Notably, fludarabine toxicity may exacerbate immune effector-associated neurotoxicity syndrome, or that dialysis-dependent patients may experience more severe encephalopathy from any cause due to abnormal renal elimination ( 127 ).

Fortunately, lymphodepleting preconditioning—typically essential to support the expansion of adoptively transferred CAR-T cells—is not required and is fundamentally unsuitable for in vivo CAR-T approaches. However, as a living therapeutic modality, the in vivo pharmacokinetic behavior of CAR-T cells is predominantly determined by immune microenvironmental factors and tumor antigen engagement—not by renal clearance mechanisms. To date, dedicated pharmacokinetic studies, large-scale clinical trials, and formal clinical practice guidelines addressing CAR-T cell therapy in patients with end-stage kidney disease requiring dialysis remain notably lacking. As a result, in vivo CAR-T cell therapy holds promise as an immunotherapeutic strategy for patients with end-stage renal disease (ESRD), as it circumvents the need for chemotherapy and enables more effective recruitment of diverse immune mechanisms, which are critical for enhancing therapeutic outcomes ( 128 ).

Collectively, the majority of treatment recommendations are based on low-quality evidence and lack support from randomized controlled trials. To date, no authoritative, evidence-based, and comprehensive clinical practice guidelines exist to guide anticancer therapy in patients undergoing hemodialysis. Pharmacokinetic data remain insufficient, particularly for novel anticancer agents such as targeted therapies and immune checkpoint inhibitors, and corresponding pharmacokinetic/pharmacodynamic studies are significantly underdeveloped. Moreover, toxicity management presents significant clinical challenges in this population, attributable to their compromised baseline health status, high burden of comorbidities, diminished tolerance to drug-induced toxicities, and difficulties in both recognizing and mitigating adverse events.

Therefore, clinicians should individualize antineoplastic therapy in patients with ESRD based on available pharmacokinetic and pharmacodynamic data, as well as current clinical recommendations.

Emerging research directions

Predict the risk of chemotherapy-induced kidney injury in tumor patients through genomic analysis and formulate individualized treatment plans

Utilize artificial intelligence and data analysis to recommend the appropriate dose as well as predict the risk of adverse effects in ESRD patients undergoing chemotherapy.

The development of targeted anti-tumor agents with reduced nephrotoxicity and minimal renal clearance

Platinum-based antineoplastic drugs delivered via O-succinyl chitosan (BSCT) self-assembling nanocarriers or tolfenamic acid-derived prodrug nanoparticles ( 48 ), as well as albumin-conjugated doxorubicin utilizing self-assembling dyes ( 76 ), represents a promising strategy for improving therapeutic efficacy while mitigating adverse effects.

Development of individualized chemotherapy regimens for hemodialysis patients guided by pharmacokinetic and pharmacodynamics principles

In the era of precision medicine, accumulating evidence suggests that conventional cytotoxic agents may be viable candidates for therapeutic drug monitoring-guided dose optimization and individualized tailoring of non-selective chemotherapy regimens. Furthermore, mass spectrometry-based methods have been established for the measurement of conventional cytotoxic anticancer agents ( 129 ).

The potential contribution of chemotherapy-associated bone disorders—including endocrine therapy and estrogen deprivation—to the pathogenesis and progression of renal osteodystrophy in patients with ESRD

Well-designed clinical studies are needed to evaluate the safety and efficacy of targeted agents such as denosumab and cinacalcet in managing hypercalcemia among uremic patients.

Conclusion

Although guidelines exist for the use of chemotherapy agents in patients with chronic kidney disease and malignancies, many questions remain unanswered, particularly regarding the pharmacokinetics and pharmacodynamics of these drugs in patients with end-stage renal disease undergoing hemodialysis. Leveraging precision medicine, susceptibility gene screening enables the identification of individuals at elevated risk for kidney injury, thereby supporting early interventions to mitigate progression from chronic kidney disease to end-stage renal disease. The optimal dose of antineoplastic agents is determined on an individual basis according to pharmacokinetic and pharmacodynamic principles to avoid adverse drug reactions resulting from excessive exposure in patients with end-stage renal disease undergoing hemodialysis. Notably, artificial intelligence holds promise as a predictive and early-alert tool for antineoplastic drug–related adverse events in patients with end-stage renal disease undergoing hemodialysis. Furthermore, the development of targeted antineoplastic agents has contributed to reduced renal toxicity and improved intratumoral drug accumulation. Future clinical trials evaluating antineoplastic therapies should prospectively enroll patients undergoing hemodialysis to improve survival outcomes and quality of life.

Funding Statement

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by Talent plan of Taihu Lake in Wuxi (HB2020047), Research project of Wuxi Municipal Health Commission (M202304) and Clinical medical research project of the Affiliated Hospital of Jiangnan University (LCYJ202329).

Footnotes

Edited by: Junmin Zhang , Lanzhou University, China

Reviewed by: Jérôme Bonzon , University Hospital Zürich, Switzerland

Ittamar Gork , Hadassah Medical Center, Israel

Author contributions

JLi: Conceptualization, Data curation, Funding acquisition, Supervision, Validation, Writing – original draft, Writing – review & editing, Project administration. QK: Data curation, Formal analysis, Writing – original draft, Project administration. WL: Data curation, Formal analysis, Writing – original draft, Project administration. DL: Data curation, Formal analysis, Project administration, Writing – original draft. JLu: Data curation, Formal analysis, Project administration, Writing – original draft.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Kitchlu A, Reid J, Jeyakumar N, Dixon SN, Munoz AM, Silver SA, et al. Cancer risk and mortality in patients with kidney disease: a population-based cohort study. Am J Kidney Dis. (2022) 80:436–448.e1. doi: 10.1053/j.ajkd.2022.02.020. PMID:

2. Gadalean F, Ciorcan M, Apostol A, Schiller O, Ivan V, Petrica L, et al. Cancer before and after the start of hemodialysis and association with mortality - an Eastern-European multicenter study. Ren Fail. (2023) 45:2232046. doi: 10.1080/0886022x.2023.2232046. PMID:

3. Lim WH, Ooi E, Pankaj A, Teixeira-Pinto A, Lin Y, Johnson DW, et al. The incidence of cancer recurrence and new cancer following commencement of dialysis. Clin Kidney J. (2022) 15:1770–81. doi: 10.1093/ckj/sfac124. PMID:

4. Delaye M, Rousseau A, Try M, Massard C, Campedel L, Hilmi M, et al. Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer. Cancer Med. (2023) 12:3172–5. doi: 10.1002/cam4.5171. PMID:

5. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. Lancet. (2015) 385:1975–82. doi: 10.1016/j.jvs.2015.08.003. PMID:

6. Chen T, Sun X, Tsuei S, Yang R, Yip W, Fu H. Care for end-stage kidney disease in China: progress, challenges, and recommendations. Lancet Reg Health West Pac. (2025) 54:101268. doi: 10.1016/j.lanwpc.2024.101268. PMID:

7. Butler AM, Olshan AF, Kshirsagar AV, Edwards JK, Nielsen ME, Wheeler SB, et al. Cancer incidence among US Medicare ESRD patients receiving hemodialysis, 1996-2009. Am J Kidney Dis. (2015) 65:763–72. doi: 10.1053/j.ajkd.2014.12.013. PMID:

8. Chen X, Li Y, Ding X, Shen B, Xiang F, Guo M, et al. Incidence, risk, and prognosis of cancer in patients on chronic hemodialysis. Blood Purif. (2020) 49:310–21. doi: 10.1159/000504243. PMID:

9. Yanik EL, Clarke CA, Snyder JJ, Pfeiffer RM, Engels EA. Variation in cancer incidence among patients with ESRD during kidney function and nonfunction intervals. J Am Soc Nephrol. (2016) 27:1495–504. doi: 10.1681/asn.2015040373. PMID:

10. Massicotte-Azarniouch D, Noel JA, Knoll GA. Epidemiology of cancer in kidney transplant recipients. Semin Nephrol. (2024) 44:151494. doi: 10.1016/j.semnephrol.2024.151494. PMID:

11. Lee MJ, Lee E, Park B, Park I. Epidemiological characteristics of cancers in patients with end-stage kidney disease: a Korean nationwide study. Sci Rep. (2021) 11:3929. doi: 10.1038/s41598-021-83164-6. PMID:

12. Taborelli M, Toffolutti F, Del Zotto S, Clagnan E, Furian L, Piselli P, et al. Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy. BMC Nephrol. (2019) 20:107. doi: 10.1186/s12882-019-1283-4. PMID:

13. Tang CH, Chen YC, Hsieh WT, Sue YM. Gender and age differences of genitourinary cancers among chronic dialysis patients in Taiwan. Clin Genitourin Cancer. (2022) 20:e126–34. doi: 10.1016/j.clgc.2021.11.013. PMID:

14. Zakrocka I, Nair G, Soler MJ, Jhaveri KD, Kronbichler A. Paraneoplastic syndrome after kidney transplantation: frequency, risk factors, differences to paraneoplastic occurrence of glomerulonephritis in the native kidney, and implications on long-term kidney graft function. Transpl Int. (2024) 37:12969. doi: 10.3389/ti.2024.12969. PMID:

15. Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transplant. (2018) 33:iii35–40. doi: 10.1093/ndt/gfy175. PMID:

16. Casella C, Dondi D, Vadivel D. Do microplastics (MPs) and nanoplastics (NPs) directly contribute to human carcinogenesis? Environ pollut. (2026) 388:127343. doi: 10.1016/j.envpol.2025.127343. PMID:

17. Hu M, Wang Q, Liu B, Ma Q, Zhang T, Huang T, et al. Chronic kidney disease and cancer: inter-relationships and mechanisms. Front Cell Dev Biol. (2022) 10:868715. doi: 10.3389/fcell.2022.868715. PMID:

18. Duong NX, Le MK, Nguyen TT, Nguyen DD, Vuong HG, Kondo T, et al. Acquired cystic disease-associated renal cell carcinoma: a systematic review and meta-analysis. Clin Genitourin Cancer. (2024) 22:102050. doi: 10.1016/j.clgc.2024.02.001. PMID:

19. Jelaković B, Castells X, Tomić K, Ardin M, Karanović S, Zavadil J. Renal cell carcinomas of chronic kidney disease patients harbor the mutational signature of carcinogenic aristolochic acid. Int J Cancer. (2015) 136:2967–72. doi: 10.1002/ijc.29338, PMID:

20. Ranjan MK, Kante B, Vuyyuru SK, Kumar P, Mundhra SK, Golla R, et al. Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: a longitudinal cohort analysis from northern India. J Gastroenterol Hepatol. (2022) 37:1544–53. doi: 10.1111/jgh.15880. PMID:

21. Rosales BM, De La Mata N, Vajdic CM, Kelly PJ, Wyburn K, Webster AC. Cancer mortality in people receiving dialysis for kidney failure: an Australian and New Zealand cohort study, 1980-2013. Am J Kidney Dis. (2022) 80:449–61. doi: 10.1053/j.ajkd.2022.03.010. PMID:

22. Stewart JH, Buccianti G, Agodoa L, Gellert R, McCredie MR, Lowenfels AB, et al. Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: analysis of data from the United States, Europe, and Australia and New Zealand. J Am Soc Nephrol. (2003) 14:197–207. doi: 10.1097/01.asn.0000039608.81046.81. PMID:

23. Funakoshi T, Horimatsu T, Nakamura M, Shiroshita K, Suyama K, Mukoyama M, et al. Chemotherapy in cancer patients undergoing hemodialysis: a nationwide study in Japan. ESMO Open. (2018) 3:e000301. doi: 10.1136/esmoopen-2017-000301. PMID:

24. Rossi R, Pleyer J, Schäfers P, Kuhn N, Kleta R, Deufel T, et al. Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75 patients. Med Pediatr Oncol. (1999) 32:177–82. doi: 10.1002/(sici)1096-911x(199903)32:3<177::aid-mpo3>3.0.co;2-h

25. Liamis G, Filippatos TD, Elisaf MS. Electrolyte disorders associated with the use of anticancer drugs. Eur J Pharmacol. (2016) 777:78–87. doi: 10.1016/j.ejphar.2016.02.064. PMID:

26. Grohé C, Berardi R, Burst V. Hyponatremia--SIADH in lung cancer diagnostic and treatment algorithms. Crit Rev Oncol Hematol. (2015) 96:1–8. doi: 10.1016/j.critrevonc.2015.04.005, PMID:

27. Tandon PK, Rizvi AA. Hypocalcemia and parathyroid function in metastatic prostate cancer. Endocr Pract. (2005) 11:254–8. doi: 10.4158/ep.11.4.254. PMID:

28. Bartkiewicz P, Kunachowicz D, Filipski M, Stebel A, Ligoda J, Rembiałkowska N. Hypercalcemia in cancer: causes, effects, and treatment strategies. Cells. (2024) 13:1051. doi: 10.3390/cells13121051. PMID:

29. Heneberg P. Lactic acidosis in patients with solid cancer. Antioxid Redox Signal. (2022) 37:1130–52. doi: 10.1089/ars.2021.0267. PMID:

30. Takahashi K, Totsune K, Kitamuro T, Sone M, Murakami O, Shibahara S. Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumor cell lines of different origin: expression and effects on proliferation. Clin Sci Lond. (2002) 103:35s–8s. doi: 10.1042/cs103s035s. PMID:

31. Kuang H, Yan Q, Li Z, Lin A, Li K, Zhang J, et al. Comprehensive analysis of VEGF/VEGFR inhibitor-induced immune-mediated hypertension: integrating pharmacovigilance, clinical data, and preclinical models. Front Immunol. (2024) 15:1488853. doi: 10.3389/fimmu.2024.1488853. PMID:

32. Cohen JB, Brown NJ, Brown SA, Dent S, van Dorst DCH, Herrmann SM, et al. Cancer therapy-related hypertension: a scientific statement from the American Heart Association. Hypertension. (2023) 80:e46–57. doi: 10.1161/hyp.0000000000000224. PMID:

33. Posado-Domínguez L, Chamorro AJ, Del Barco-Morillo E, Martín-Galache M, Bueno-Sacristán D, Fonseca-Sánchez E, et al. Cancer-associated thrombotic microangiopathy: literature review and report of five cases. Life Bsl. (2024) 14:865. doi: 10.3390/life14070865. PMID:

34. Decaestecker A, Hamroun A, Provot F, Rondeau E, Faguer S, Sallee M, et al. Retrospective study of 59 cases of cancer-associated thrombotic microangiopathy: presentation and treatment characteristics. Nephrol Dial Transplant. (2023) 38:913–21. doi: 10.1093/ndt/gfac213. PMID:

35. Hassamal S, Miotto K, Dale W, Danovitch I. Tramadol: understanding the risk of serotonin syndrome and seizures. Am J Med. (2018) 131:1382.e1–1382.e6. doi: 10.1016/j.amjmed.2018.04.025. PMID:

36. Pilleron S, Alqurini N, Ferlay J, Haase KR, Hannan M, Janssen-Heijnen M, et al. International trends in cancer incidence in middle-aged and older adults in 44 countries. J Geriatr Oncol. (2022) 13:346–55. doi: 10.1016/j.jgo.2021.11.011. PMID:

37. Jang SM, Awdishu L. Drug dosing considerations in continuous renal replacement therapy. Semin Dial. (2021) 34:480–8. doi: 10.1111/sdi.12972. PMID:

38. Tesseromatis C, Alevizou A. The role of the protein-binding on the mode of drug action as well the interactions with other drugs. Eur J Drug Metab Pharmacokinet. (2008) 33:225–30. doi: 10.1007/bf03190876. PMID:

39. Launay-Vacher V, Izzedine H, Baumelou A, Deray G. FHD: an index to evaluate drug elimination by hemodialysis. Am J Nephrol. (2005) 25:342–51. doi: 10.1159/000086591. PMID:

40. Yang Q, Han E, Xu S, Xu Y, Gao J. Treatment of advanced ovarian cancer with carboplatin and paclitaxel in a patient undergoing hemodialysis: case report and literature review. Hemodial Int. (2022) 26:E31–6. doi: 10.1111/hdi.13020. PMID:

41. Bucher MC, Bossard DA, Bonani M, Paul M, Geinitz C, Bonzon J. Carboplatin therapeutic drug monitoring in intermittent hemodialysis-a case report and review of the literature. Clin Ther. (2025) 47:450–5. doi: 10.1016/j.clinthera.2025.02.007. PMID:

42. Fong MK, Fetterly GJ, McDougald LJ, Iyer RV. Carboplatin pharmacokinetics in a patient receiving hemodialysis. Pharmacotherapy. (2014) 34:e9–e13. doi: 10.1002/phar.1354. PMID:

43. Minegishi Y, Akagami T, Arai M, Saito R, Arai D, Murase K, et al. Real-world outcomes of chemotherapy for lung cancer patients undergoing hemodialysis: a multicenter retrospective cohort study (NEJ-042). Lung Cancer. (2022) 172:1–8. doi: 10.2139/ssrn.4082293. PMID:

44. Pedrazzoli P, Silvestris N, Santoro A, Secondino S, Brunetti O, Longo V, et al. Management of patients with end-stage renal disease undergoing chemotherapy: recommendations of the Associazione Italiana di Oncologia Medica (AIOM) and the Società Italiana di Nefrologia (SIN). ESMO Open. (2017) 2:e000167. doi: 10.1136/esmoopen-2017-000167. PMID:

45. Hirakawa H, Nakashima C, Nakamura T, Masuda M, Funakoshi T, Nakagawa S, et al. Chemotherapy for primary mediastinal yolk sac tumor in a patient undergoing chronic hemodialysis: a case report. J Med Case Rep. (2017) 11:43. doi: 10.1186/s13256-017-1213-7. PMID:

46. Maruta M, Miyoshi T, Matsuo N, Yamashina T, Irie K, Tsuruta M, et al. Clinical pharmacokinetics of oxaliplatin in a hemodialysis patient with advanced gastric cancer. J Chemother. (2021) 33:51–5. doi: 10.1080/1120009x.2020.1728861. PMID:

47. Oronsky B, Caroen S, Oronsky A, Dobalian VE, Oronsky N, Lybeck M, et al. Electrolyte disorders with platinum-based chemotherapy: mechanisms, manifestations and management. Cancer Chemother Pharmacol. (2017) 80:895–907. doi: 10.1007/s00280-017-3392-8. PMID:

48. Ma X, Liu Y, Wu H, Tan J, Yi W, Wang Z, et al. Self-assembly nanoplatform of platinum (IV) prodrug for enhanced ovarian cancer therapy. Mater Today Bio. (2023) 21:100698. doi: 10.1016/j.mtbio.2023.100698. PMID:

49. Vénat-Bouvet L, Saint-Marcoux F, Lagarde C, Peyronnet P, Lebrun-Ly V, Tubiana-Mathieu N. Irinotecan-based chemotherapy in a metastatic colorectal cancer patient under hemodialysis for chronic renal dysfunction: two cases considered. Anticancer Drugs. (2007) 18:977–80. doi: 10.1097/cad.0b013e32811d69cb. PMID:

50. Stemmler J, Weise A, Hacker U, Heinemann V, Schalhorn A. Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure. Onkologie. (2002) 25:60–3. doi: 10.1159/000055204. PMID:

51. Huang SH, Chao Y, Wu YY, Luo JC, Kao CH, Yen SH, et al. Concurrence of UGT1A polymorphism and end-stage renal disease leads to severe toxicities of irinotecan in a patient with metastatic colon cancer. Tumori. (2011) 97:243–7. doi: 10.1177/030089161109700221. PMID:

52. Henwood JM, Brogden RN. Etoposide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. Drugs. (1990) 39:438–90. doi: 10.2165/00003495-199039030-00008, PMID:

53. Watanabe R, Takiguchi Y, Moriya T, Oda S, Kurosu K, Tanabe N, et al. Feasibility of combination chemotherapy with cisplatin and etoposide for hemodialysis patients with lung cancer. Br J Cancer. (2003) 88:25–30. doi: 10.1038/sj.bjc.6600687. PMID:

54. Imamaki H, Oura M, Oguro F, Nishikawa Y, Nakagawa S, Funakoshi T, et al. Removal rate of 5-fluorouracil and its metabolites in patients on hemodialysis: a report of two cases of colorectal cancer patients with end-stage renal failure. Cancer Chemother Pharmacol. (2024) 93:161–7. doi: 10.1007/s00280-023-04577-w. PMID:

55. Katamura Y, Aikata H, Kimura Y, Azakami T, Kawaoka T, Takaki S, et al. Successful treatment of pulmonary metastases associated with advanced hepatocellular carcinoma by systemic 5-fluorouracil combined with interferon-alpha in a hemodialysis patient. Hepatol Res. (2009) 39:415–20. doi: 10.1111/j.1872-034x.2008.00448.x. PMID:

56. Yeung EK, Copland MA, Gill S. Type B lactic acidosis from fluorouracil in fluorouracil, oxaliplatin and leucovorin treatment for carcinoma of the colon in a hemodialysis patient. Clin Kidney J. (2018) 11:786–7. doi: 10.1093/ckj/sfy012. PMID:

57. Iida T, Wagatsuma K, Tani M, Sasaki H, Naganawa Y, Isshiki H, et al. Four cases of 5-fluorouracil-related hyperammonemia in patients with large intestinal cancer and multiple liver metastases, including a case of hyperammonemia treated using hemodialysis. Nihon Shokakibyo Gakkai Zasshi. (2015) 112:287–96. doi: 10.11405/nisshoshi.112.287, PMID:

58. Hann A, Nosalski E, Hermann PC, Egger J, Seufferlein T, Keller F. Chemotherapeutic agents eligible for prior dosing in pancreatic cancer patients requiring hemodialysis: a systematic review. Clin Nephrol. (2018) 90:125–41. doi: 10.5414/cn109327. PMID:

59. Poole C, Gardiner J, Twelves C, Johnston P, Harper P, Cassidy J, et al. Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients. Cancer Chemother Pharmacol. (2002) 49:225–34. doi: 10.1007/s00280-001-0408-0. PMID:

60. Jhaveri KD, Flombaum C, Shah M, Latcha S. A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR <30 mL/min) and end stage renal disease on hemodialysis. J Oncol Pharm Pract. (2012) 18:140–7. doi: 10.1177/1078155210390255. PMID:

61. Derissen EJB, Huitema ADR, Rosing H, Schellens JHM, Beijnen JH. Intracellular pharmacokinetics of gemcitabine, its deaminated metabolite 2’,2’-difluorodeoxyuridine and their nucleotides. Br J Clin Pharmacol. (2018) 84:1279–89. doi: 10.1111/bcp.13557. PMID:

62. Kiani A, Köhne CH, Franz T, Passauer J, Haufe T, Gross P, et al. Pharmacokinetics of gemcitabine in a patient with end-stage renal disease: effective clearance of its main metabolite by standard hemodialysis treatment. Cancer Chemother Pharmacol. (2003) 51:266–70. doi: 10.1007/s00280-003-0574-3. PMID:

63. Matsumoto K, Okamoto K, Namura Y, Kikuyama T, Saito G, Adachi T, et al. Chemotherapy with gemcitabine for unresectable intrahepatic cholangiocarcinoma in a patient undergoing maintenance hemodialysis. Clin J Gastroenterol. (2021) 14:1511–6. doi: 10.1007/s12328-021-01478-4. PMID:

64. Nascimento de Assis TCF, Rapatoni L, Segato FN, Maciel Pontes BT, Muglia VF, Neto MM, et al. Effective treatment of collecting duct carcinoma in a recipient of a kidney transplant: A case report. Oncol Lett. (2024) 28:528. doi: 10.3892/ol.2024.14661. PMID:

65. Abushanab D, Mohamed S, Abdel-Latif R, Moustafa DA, Marridi W, Elazzazy S, et al. Dihydropyrimidine dehydrogenase deficiency (DPYD) genotyping-guided fluoropyrimidine-based adjuvant chemotherapy for breast cancer. A cost-effectiveness analysis. Clin Drug Investig. (2025) 45:151–63. doi: 10.1007/s40261-024-01413-8. PMID:

66. Gaible C, Narjoz C, Loriot MA, Roueff S, Pallet N. Pretherapeutic screening for Dihydropyrimidine deshydrogenase deficiency in measuring uracilemia in dialysis patients leads to a high rate of falsely positive results. Cancer Chemother Pharmacol. (2021) 88:1049–53. doi: 10.1007/s00280-021-04354-7. PMID:

67. Rollino C, Milongo R, Schaerer R, Cordonnier D. Vinorelbine therapy in a hemodialyzed patient. Nephron. (1992) 61:232–3. doi: 10.1159/000186882. PMID:

68. Matsumoto M, Yano H, Otsubo R, Tanaka A, Nagayasu T. Favorable survival with combined treatment in a metastatic breast cancer patient undergoing hemodialysis: A case report. Int J Surg Case Rep. (2021) 79:206–9. doi: 10.1016/j.ijscr.2021.01.044. PMID:

69. Baur M, Fazeny-Doerner B, Olsen SJ, Dittrich C. High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature. Int J Gynecol Cancer. (2008) 18:564–70. doi: 10.1111/j.1525-1438.2007.01048.x. PMID:

70. Yang L, Zhang XC, Yu SF, Zhu HQ, Hu AP, Chen J, et al. Pharmacokinetics and safety of cyclophosphamide and docetaxel in a hemodialysis patient with early stage breast cancer: a case report. BMC Cancer. (2015) 15:917. doi: 10.1186/s12885-015-1932-3. PMID:

71. Zhao Y, Wang P, Wang Y, Zhang L, Zhao Y, Li H, et al. Drug-coated balloon angioplasty for dysfunctional arteriovenous hemodialysis fistulae: A randomized controlled trial. Clin J Am Soc Nephrol. (2024) 19:336–44. doi: 10.2215/cjn.0000000000000359. PMID:

72. Loo KCY, Lim YN, Kiu DKL, Sim WW. Gestational trophoblastic neoplasm in a patient with end-stage renal failure (ESRF): the challenges and lessons learnt. BMJ Case Rep. (2022) 15:e249474. doi: 10.1136/bcr-2022-249474. PMID:

73. Hunz M, Jetter A, Warm M, Pantke E, Tuscher M, Hempel G, et al. Plasma and tissue pharmacokinetics of epirubicin and Paclitaxel in patients receiving neoadjuvant chemotherapy for locally advanced primary breast cancer. Clin Pharmacol Ther. (2007) 81:659–68. doi: 10.1038/sj.clpt.6100067. PMID:

74. Yoshida H, Goto M, Honda A, Nabeshima T, Kumazawa T, Inagaki J, et al. Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis. Cancer Chemother Pharmacol. (1994) 33:450–4. doi: 10.1007/bf00686499. PMID:

75. Hochegger K, Lhotta K, Mayer G, Czejka M, Hilbe W. Pharmacokinetic analysis of docetaxel during hemodialysis in a patient with locally advanced non-small cell lung cancer. Nephrol Dial Transplant. (2007) 22:289–90. doi: 10.1093/ndt/gfl498. PMID:

76. Jagusiak A, Chłopaś K, Zemanek G, Kościk I, Skorek P, Stopa B. Albumin binds doxorubicin via self-assembling dyes as specific polymolecular ligands. Int J Mol Sci. (2022) 23:5033. doi: 10.3390/ijms23095033. PMID:

77. Haubitz M, Bohnenstengel F, Brunkhorst R, Schwab M, Hofmann U, Busse D. Cyclophosphamide pharmacokinetics and dose requirements in patients with renal insufficiency. Kidney Int. (2002) 61:1495–501. doi: 10.1046/j.1523-1755.2002.00279.x. PMID:

78. Yasuda H, Yasuda M, Komatsu N. Chemotherapy for non-Hodgkin lymphoma in the hemodialysis patient: A comprehensive review. Cancer Sci. (2021) 112:2607–24. doi: 10.1111/cas.14933. PMID:

79. Carlson L, Goren MP, Bush DA, Griener JC, Quigley R, Tkaczewski I, et al. Ifosfamide may be safely used in patients with end stage renal disease on hemodialysis. Sarcoma. (2009) 2009:575629. doi: 10.1155/2009/575629, PMID:

80. Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. (1996) 124:477–84. doi: 10.7326/0003-4819-124-5-199603010-00003. PMID:

81. Zeng Y, Arisa O, Peer CJ, Fojo A, Figg WD. PARP inhibitors: A review of the pharmacology, pharmacokinetics, and pharmacogenetics. Semin Oncol. (2024) 51:19–24. doi: 10.1053/j.seminoncol.2023.09.005. PMID:

82. Baum J, Zickler D, Bolbrinker J, Richter R, Braicu EI, Grabowski J, et al. Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis. Cancer Chemother Pharmacol. (2023) 91:325–30. doi: 10.1007/s00280-023-04514-x. PMID:

83. Garnier-Viougeat N, Rixe O, Paintaud G, Ternant D, Degenne D, Mouawad R, et al. Pharmacokinetics of bevacizumab in hemodialysis. Nephrol Dial Transplant. (2007) 22:975. doi: 10.1093/ndt/gfl664. PMID:

84. Klajer E, Garnier L, Goujon M, Schlurmann-Constans F, Mery B, Nguyen Tan Hon T, et al. Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review. Semin Oncol. (2020) 47:103–16. doi: 10.1053/j.seminoncol.2020.05.001. PMID:

85. Shetty AV, Matrana MR, Atkinson BJ, Flaherty AL, Jonasch E, Tannir NM, et al. Outcomes of patients with metastatic renal cell carcinoma and end-stage renal disease receiving dialysis and targeted therapies: a single institution experience. Clin Genitourin Cancer. (2014) 12:348–53. doi: 10.1016/j.clgc.2014.01.004. PMID:

86. Díaz-González Á, Sanduzzi-Zamparelli M, da Fonseca LG, Di Costanzo GG, Alves R, Iavarone M, et al. International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis. Liver Int. (2020) 40:1467–76. doi: 10.1111/liv.14436. PMID:

87. Kennoki T, Kondo T, Kimata N, Murakami J, Ishimori I, Nakazawa H, et al. Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center. Jpn J Clin Oncol. (2011) 41:647–55. doi: 10.1093/jjco/hyr015. PMID:

88. Izzedine H, Etienne-Grimaldi MC, Renée N, Vignot S, Milano G. Pharmacokinetics of sunitinib in hemodialysis. Ann Oncol. (2009) 20:190–2. doi: 10.1093/annonc/mdn626. PMID:

89. Nguyen L, Holland J, Ramies D, Mamelok R, Benrimoh N, Ciric S, et al. Effect of renal and hepatic impairment on the pharmacokinetics of cabozantinib. J Clin Pharmacol. (2016) 56:1130–40. doi: 10.1002/jcph.714. PMID:

90. Bolonesi RM, Rogers JE, Shureiqi I. A case report—Treatment of metastatic colorectal cancer in a patient on hemodialysis. J gastrointestinal Cancer. (2014) 45:161–5. doi: 10.1007/s12029-014-9611-1. PMID:

91. Nakashima S, Sekine A, Sawa N, Kawamura Y, Kono K, Kinowaki K, et al. Thrombotic microangiopathy, podocytopathy, and damage to the renal tubules with severe proteinuria and acute renal dysfunction induced by lenvatinib. Intern Med. (2022) 61:3083–8. doi: 10.2169/internalmedicine.8365-21. PMID:

92. Shen H, Yang Z, Zhao W, Zhang Y, Rodrigues AD. Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance. Drug Metab Dispos. (2013) 41:2095–103. doi: 10.1124/dmd.113.053215. PMID:

93. Nakai K, Fujii H, Kono K, Goto S, Nishi S. Hypertension induced by tyrosine-kinase inhibitors for the treatment of renal cell carcinoma in hemodialysis patients: A single-center experience and review of the literature. Ther Apher Dial. (2017) 21:320–5. doi: 10.1111/1744-9987.12537. PMID:

94. Czarnecka AM, Kawecki M, Lian F, Korniluk J, Szczylik C. Feasibility, efficacy and safety of tyrosine kinase inhibitor treatment in hemodialyzed patients with renal cell cancer: 10 years of experience. Future Oncol. (2015) 11:2267–82. doi: 10.2217/fon.15.112. PMID:

95. Lan CC, Hsieh PC, Huang CY, Yang MC, Su WL, Wu CW, et al. Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis. World J Clin cases. (2022) 10:6360–9. doi: 10.12998/wjcc.v10.i19.6360. PMID:

96. Imai H, Kaira K, Naruse I, Hayashi H, Iihara H, Kita Y, et al. Successful afatinib treatment of advanced non-small-cell lung cancer patients undergoing hemodialysis. Cancer Chemother Pharmacol. (2017) 79:209–13. doi: 10.1007/s00280-016-3201-9. PMID:

97. De Luca I, Miliziano D, Guerra G, Colombo R, Morosi C, Sposito C, et al. Hemodialysis and imatinib: Plasma levels, efficacy and tolerability in a patient with metastatic GIST - Case report. Heliyon. (2024) 10:e28494. doi: 10.1016/j.heliyon.2024.e28494. PMID:

98. Wada Y, Ogata H, Misawa S, Shimada A, Kinugasa E. A hemodialysis patient with primary extra-gastrointestinal stromal tumor: favorable outcome with imatinib mesylate. Intern Med. (2012) 51:1561–5. doi: 10.2169/internalmedicine.51.6709. PMID:

99. Lunardi G, Armirotti A, Nicodemo M, Cavallini L, Damonte G, Vannozzi MO, et al. Comparison of temsirolimus pharmacokinetics in patients with renal cell carcinoma not receiving dialysis and those receiving hemodialysis: a case series. Clin Ther. (2009) 31:1812–9. doi: 10.1016/j.clinthera.2009.08.018. PMID:

100. Omae K, Kondo T, Takagi T, Iizuka J, Kobayashi H, Hashimoto Y, et al. Use of mammalian target of rapamycin inhibitors after failure of tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma undergoing hemodialysis: A single-center experience with four cases. Hemodial Int. (2016) 20:E1–5. doi: 10.1111/hdi.12390. PMID:

101. Miyake H, Harada K, Kusuda Y, Fujisawa M. Efficacy and safety of temsirolimus in Japanese patients with metastatic renal cell carcinoma on hemodialysis. Int J Clin Oncol. (2013) 18:1054–9. doi: 10.1007/s10147-012-0492-7. PMID:

102. González A, Garcia P, Gastaldo A, Simón I, Boffil J, Borrego M. Safety and efficacy of trastuzumab emtansine (TDM-1) in a patient on hemodialysis for renal failure. Cancer Treat Res Commun. (2021) 27:100314. doi: 10.1016/j.ctarc.2021.100314, PMID:

103. Gaertner K, Poornima I, Hilton C. Trastuzumab and pertuzumab in hemodialysis: A case report. J Oncol Pharm Pract. (2021) 27:1799–801. doi: 10.1177/10781552211003641. PMID:

104. Pai S, Chaikin P, Berg J. Pharmacokinetics of lapatinib, a nonrenally cleared drug, in patients with end-stage renal disease on maintenance hemodialysis. J Clin Pharmacol. (2019) 59:1379–83. doi: 10.1002/jcph.1430. PMID:

105. Park J, Boddy A, Liu X, Harris D, Lee V, Kefford R, et al. Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing hemodialysis. Pigment Cell Melanoma Res. (2017) 30:68–71. doi: 10.14309/00000434-201510001-01221. PMID:

106. Hayakawa K, Wakimoto H, Mae K, Irisawa R, Harada K. Efficacy and safety of full-dose dabrafenib and trametinib combination therapy in a patient on hemodialysis with metastatic melanoma. Int J Dermatol. (2021) 60:516–7. doi: 10.1111/ijd.15298. PMID:

107. Iddawela M, Crook S, George L, Lakkaraju A, Nanayakkara N, Hunt R, et al. Safety and efficacy of vemurafenib in end stage renal failure. BMC Cancer. (2013) 13:581. doi: 10.1186/1471-2407-13-581. PMID:

108. Yu Y, Hoffman J, Plotka A, O’Gorman M, Shi H, Wang D. Palbociclib (PD-0332991) pharmacokinetics in subjects with impaired renal function. Cancer Chemother Pharmacol. (2020) 86:701–10. doi: 10.1007/s00280-020-04163-4. PMID:

109. Takakura T, Iwasa T, Imamura C, Watanabe S, Hayashi H. Pharmacokinetics, efficacy and safety of palbociclib and fulvestrant in a patient with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with end-stage renal disease undergoing hemodialysis: A case report. Invest New Drugs. (2025) 43:764–9. doi: 10.1007/s10637-025-01564-1. PMID:

110. Heilberg I, Hernandez E, Alonzo E, Valera R, Ferreira L, Gomes S, et al. Estrogen receptor (ER) gene polymorphism may predict the bone mineral density response to raloxifene in postmenopausal women on chronic hemodialysis. Ren Fail. (2005) 27:155–61. doi: 10.1081/jdi-48241

111. Langenegger T, Wahl P, Schiesser D, Thürlimann B. Plasma levels of tamoxifen, N-desmethyl tamoxifen and anastrozole in a patient with metastatic breast cancer and chronic hemodialysis. Breast Cancer Res Treat. (2006) 100:177–81. doi: 10.1007/s10549-006-9243-7. PMID:

112. Yeh S, Marandi M, Thode H, Levine D, Parker T, Dixon T, et al. Report of a pilot, double-blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. (2010) 20:52–62. doi: 10.1053/j.jrn.2009.08.005. PMID:

113. Keizer R, Huitema A, Schellens J, Beijnen J. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. (2010) 49:493–507. doi: 10.2165/11531280-000000000-00000. PMID:

114. Centanni M, Moes D, Trocóniz I, Ciccolini J, van Hasselt J. Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clin Pharmacokinet. (2019) 58:835–57. doi: 10.1007/s40262-019-00748-2. PMID:

115. Highlights of prescribing Opdivo (Nivolumab). FDA guidelines. Available online at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125554lbl.pdf . Reference ID: 3677021 1 (Accessed May 8, 2019).

116. Kitchlu A, Jhaveri K, Sprangers B, Yanagita M, Wanchoo R. Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review. Clin Kidney J. (2021) 14:2012–22. doi: 10.1093/ckj/sfab090. PMID:

117. Mroue A, Moujaess E, Kourie H, Azar H, Finianos S, Chelala D. Exploring the knowledge gap of immune checkpoint inhibitors in chronic renal failure: A systematic review of the literature. Crit Rev Oncol Hematol. (2021) 157:103169. doi: 10.1016/j.critrevonc.2020.103169. PMID:

118. Cuzzubbo S, Javeri F, Tissier M, Roumi A, Barlog C, Doridam J, et al. Neurological adverse events associated with immune checkpoint inhibitors: Review of the literature. Eur J Cancer. (2017) 73:1–8. doi: 10.1016/j.ejca.2016.12.001. PMID:

119. Tachibana H, Kondo T, Ishihara H, Takagi T, Tanabe K. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma and end-stage renal disease at 2 centers. Clin Genitourin Cancer. (2019) 17:e772–8. doi: 10.1016/j.clgc.2019.04.004. PMID:

120. Bowry S, Kircelli F, Himmele R, Nigwekar S. Blood-incompatibility in hemodialysis: alleviating inflammation and effects of coagulation. Clin Kidney J. (2021) 14:i59–71. doi: 10.1093/ckj/sfab185. PMID:

121. Brahmer J, Lacchetti C, Schneider B, Atkins M, Brassil K, Caterino J, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline. J Clin Oncol. (2018) 36:1714–68. doi: 10.1200/jop.18.00005. PMID:

122. Brahmer J, Abu-Sbeih H, Ascierto P, Brufsky J, Cappelli L, Cortazar F, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. (2021) 9:e002435. doi: 10.1136/jitc-2021-002435. PMID:

123. Pinto E, Lione L, Compagnone M, Paccagnella M, Salvatori E, Greco M, et al. From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy. J Transl Med. (2025) 23:10. doi: 10.1186/s12967-024-06052-3. PMID:

124. Maalej K, Merhi M, Inchakalody V, Mestiri S, Alam M, Maccalli C, et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Mol Cancer. (2023) 22:20. doi: 10.1186/s12943-023-01723-z. PMID:

125. Hunter B, Hoda D, Nguyen A, Gouw L, Huber B, Jensen R, et al. Successful administration of chimeric antigen receptor (CAR) T-cell therapy in patients requiring hemodialysis. Exp Hematol Oncol. (2022) 11:10. doi: 10.1186/s40164-022-00266-1. PMID:

126. Wood A, Perez A, Arciola B, Patel K, Johnson G, DiMaggio E, et al. Outcomes of CD19-targeted chimeric antigen receptor T cell therapy for patients with reduced renal function including dialysis. Transplant Cell Ther. (2022) 28:829.e1–8. doi: 10.1016/j.jtct.2022.09.009. PMID:

127. Liu Y, Chen X, Wang D, Li H, Huang J, Zhang Z, et al. Hemofiltration successfully eliminates severe cytokine release syndrome following CD19 CAR-T-cell therapy. J Immunother. (2018) 41:406–10. doi: 10.1097/cji.0000000000000243. PMID:

128. Bot A, Scharenberg A, Friedman K, Guey L, Hofmeister R, Andorko J, et al. In vivo chimeric antigen receptor (CAR)-T cell therapy. Nat Rev Drug Discov. (2025) 25:116–37. doi: 10.1038/s41573-025-01291-5, PMID:

129. Hirasawa T, Kikuchi M, Shigeta K, Takasaki S, Sato Y, Sato T, et al. High-throughput liquid chromatography/electrospray ionization-tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma. BioMed Chromatogr. (2021) 35:e5124. doi: 10.1002/bmc.5124. PMID: