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Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience.

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The

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… The same author used temozolomide during whole-brain radiotherapy and metronomic vinorelbine afterwards in 36 patients with cerebral metastasis; OR was 52%. [ 85 ]. … CP, Cyclophosphamide; TMZ, Temozolomide. …

Oral chemotherapy agents in cats: clinical uses, administration and side effects.

PRACTICAL RELEVANCE: Cancer is a very common disease in cats, and many feline patients will require chemotherapy as part of their treatment plan, either as a sole agent or as part of multimodality therapy. Although some general practitioners might be reluctant to undertake injectable chemotherapy, oral chemotherapy may feel like a more acceptable treatment option to manage in practice. CLINICAL CHALLENGES: The small body size of many cats means that tablet sizes made for the human market are less appropriate, which creates dosing challenges. The administration of oral medication can also be a

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… Alkylating agents include cyclophosphamide, chlorambucil, lomustine, melphalan, procarbazine and temozolomide ( Figure 7 ). … Due to toxicity, temozolomide is currently not recommended for use in cats. …

Advances of DNA Damage Repair-Related Drugs and Combination With Immunotherapy in Tumor Treatment.

Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsi

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… . | Temozolomide | DNA alkylating agent | Brain cancers; astrocytoma; glioblastoma | Combine with PD-1 inhibitor in glioma Olaparib in combination with temozolomide demonstrated substantial clinical activity in relapsed small cell lung cancer Camptothecin | TOP1 | Gastric cancer; esophageal cancer, … Temozolomide Temozolomide (TMZ) is one of the widely used chemotherapy drugs targeting DDR. Studies showed that O6 methylguanine (O6 MeG) is the main cytotoxic DNA damage ( 10 ). TMZ can methylate DNA, which most often occurs at the N-7 or O-6 positions of guanine residues. …

Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, pa

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… However, the BBB penetration of temozolomide in vivo was 20% greater in Abcb1a/b knockout mice compared to wild type (WT) mice 147 . These results suggested that using an ABCB1 inhibitor with temozolomide could increase the efficacy of temozolomide in the treatment of high-grade glioblastomas. … This finding was further validated when temozolomide was combined with the dual ABCB1/ABCG2 inhibitor, elacridar. Elacridar significantly increases temozolomide penetration across the BBB in WT mice 147 . …

Drug Repurposing of New Treatments for Neuroendocrine Tumors.

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metas

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… Thereby, although early-phase studies indicated the potential efficacy of thalidomide in combination with temozolomide, further phase II studies investigating the combination in advanced/metastatic pancreatic and non-pancreatic NETs showed that S-1/temozolomide with or without thalidomide led to a comparable … S-1/temozolomide versus S-1/temozolomide plus thalidomide in advanced pancreatic and non-pancreatic neuroendocrine tumours (STEM): A randomised, open-label, multicentre phase 2 trial EClinicalMedicine 2022 54 101667 10.1016/j.eclinm.2022.101667 36188432 PMC9520203 38. Vázquez-Borrego M.C. …

Breathlessness with pulmonary metastases: a multimodal approach.

Case Study  Sarah is a 58-year-old breast cancer survivor, social worker, and health-care administrator at a long-term care facility. She li … osis. While the treatment options for her lung lesions included interleukin-2, ipilimumab (Yervoy), temozolomide, dacarbazine, a clinical trial, or radiosurgery, Sarah's oncologist felt that ipilimumab or radiosurgery would be the best course of action. She shared with her support group that she was ambivalent about this decision, as she had experienced profou …

High-Dose Continuous Infusion Ifosfamide as Effective Palliation in a Patient With Relapsed Ewing Sarcoma With Bone Marrow Infiltration and Severe Thrombocytopenia: A Case Report.

BackgroundEwing sarcoma is a rare primary mesenchymal tumor of the bone that requires an intensive multimodal therapeutic approach. Multidrug chemotherapy regimens are also the backbone for relapsing/recurring Ewing sarcoma treatment, yet when the disease relapses as bone marrow infiltration, combination chemotherapy might be difficult to administer and prognosis is poor.CaseThis report describes the case of a 22-year-old patient with Ewing sarcoma who developed severe pancytopenia due to bone marrow infiltration, and who was treated with high-dose continuous infusion ifosfamide, obtaining bot

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… Other effective chemotherapy regimens like temozolomide and irinotecan, which are commonly used in relapsed Ewing sarcoma [ 24 ], might be more challenging to resort to due to their known toxicity profile: temozolomide has a typical hematological toxicity, with not negligible rates of neutropenia and … L., Setola E., et al., “Irinotecan and Temozolomide in Recurrent Ewing Sarcoma: An Analysis in 51 Adult and Pediatric Patients,” Acta Oncologica 57, no. 7 (2018): 958–964, 10.1080/0284186X.2018.1449250. …

Marizomib in the therapy of brain tumors-how far did we go and where do we stand?

Out of several types of tumors of the central nervous system (CNS), glioblastoma (GBM) represents one of the most frequent and malignant forms of brain neoplasms. To date, GBM holds very limited therapeutic options leaving patients with poor prognosis of survival. As such, novel treatment approaches are constantly quested. One of these strategies is based on the utilization of proteasome inhibitors (PIs). However, although several PIs have been approved as therapy for patients with hematological malignancies, these treatment benefits cannot not be easily extrapolated to brain tumors. This is m

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… So far, the standard of care for GBM has been maximal possible tumor resection, followed by concurrent radiotherapy and chemotherapy with temozolomide (TMZ) [ 8 ]. … Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients. J Neurooncol. 2004;66:203–8. 10.1023/b:neon.0000013479.64348.69. 15015788 10.1023/b:neon.0000013479.64348.69 11. …

The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers.

Perillyl alcohol (POH) is a naturally occurring monoterpenoid related to limonene that is present in the essential oils of various plants. It has diverse applications and can be found in household items, including foods, cosmetics, and cleaning supplies. Over the past three decades, it has also been investigated for its potential anticancer activity. Clinical trials with an oral POH formulation administered to cancer patients failed to realize therapeutic expectations, although an intra-nasal POH formulation yielded encouraging results in malignant glioma patients. Based on its amphipathic nat

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… The current standard of care for GBM consists of surgery (if possible), followed by chemoradiation, which consists of oral temozolomide (TMZ; Temodar ® ) combined with ionizing radiation. TMZ is a prodrug that releases diazomethane, which is an alkylating agent. … Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients Clin. Cancer Res. 2004 10 3728 3736 10.1158/1078-0432.CCR-03-0807 15173079 17. Portnow J. Badie B. Chen M. Liu A. Blanchard S. Synold T. …

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

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… Temozolomide (TMZ) is the most often used and a successful alkylating chemotherapeutic drug for gliomas. A study revealed that TMZ can induce mutational load to a subset of gliomas that endorse tumor recurrence [ 20 ]. … In another study, a combination of resveratrol and temozolomide showed synergistic antiproliferative effects. …

Modeling treatment-dependent glioma growth including a dormant tumor cell subpopulation.

BackgroundTumors comprise a variety of specialized cell phenotypes adapted to different ecological niches that massively influence the tumor growth and its response to treatment.MethodsIn the background of glioblastoma multiforme, a highly malignant brain tumor, we consider a rapid proliferating phenotype that appears susceptible to treatment, and a dormant phenotype which lacks this pronounced proliferative ability and is not affected by standard therapeutic strategies. To gain insight in the dynamically changing proportions of different tumor cell phenotypes under different treatment conditi

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… We treated these cells for 10 days with temozolomide (TMZ), the most commonly used cytotoxic drug in glioma therapy. … Given are mean values of cell counting ± SD from n = 6 independent experiments Fig. 2 a Decrease of total cell numbers upon different temozolomide (TMZ) treatment strength. …

Radiotherapy and "new" drugs-new side effects?

Background and purposeTargeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic t

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… The treatment of malignant tumours of the brain has been subject to a variety of studies combining radiotherapy with bevacizumab with or without temozolomide; regarding progression-free survival, these trials suggest a benefit of the combined use [ 67 ]. … In malignant glioma, thalidomide was used in combination with radiotherapy or radiotherapy plus temozolomide in primary or recurrent settings [ 94 ]. Intratumoural bleeding and thromboembolic complications have been reported. …

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy

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… The standard treatment regimen for adult GBM patients involves post-surgical radiotherapy in conjunction with temozolomide (TMZ) chemotherapy. … Gut microbiota mediated the individualized efficacy of Temozolomide via immunomodulation in glioma. J Transl Med. 2023;21(1):198. doi: 10.1186/s12967-023-04042-5. 4. Roh TH, Kang SG, Moon JH, Sung KS, Park HH, Kim SH, et al. …

Systematic Review of Intravenous Ascorbate in Cancer Clinical Trials.

BackgroundAscorbate (vitamin C) has been evaluated as a potential treatment for cancer as an independent agent and in combination with standard chemotherapies. This review assesses the evidence for safety and clinical effectiveness of intravenous (IV) ascorbate in treating various types of cancer.MethodsSingle arm and randomized Phase I/II trials were included in this review. The PubMed, MEDLINE, and Cochrane databases were searched. Results were screened by three of the authors (GN, RP, and CJP) to determine if they met inclusion criteria, and then summarized using a narrative approach.Result

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… Schoenfeld et al. (2017) reported a phase I study with glioblastoma (GBM) patients ( n = 13) receiving pharmacological ascorbate with radiation and temozolomide [ 30 ]. … In the Phase II trials, ascorbate is being tested in combination with gemcitabine and nab-paclitaxel ( NCT02905578 ), temozolomide and radiation therapy ( NCT02344355 ). …

Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma.

BackgroundDespite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression-free survival (PFS) and overall survival (OS).MethodsWe conducted a systematic review to identify randomized controlled trial

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… Recognized as a reference drug in the treatment of newly diagnosed patients, 15 the use of temozolomide (TMZ) appears challenging in the treatment of rGBM patients with MGMT (O 6- methylguanine-DNA-methyl-transferase) promoter methylated tumors. … ACTR-56: a 2-part safety and exploratory efficacy randomised double-blind, placebo-controlled study of a 1:1 ratio of cannabidiol and delta9-tetrahydrocannabinol (CBD:THC) plus doseintense temozolomide in patients with recurrent glioblastoma multiforme (GBM). …

Characterization and treatment outcomes of malignant histiocytoses in a retrospective series of 141 cases in France.

AbstractMalignant histiocytoses (MH) are rare and poorly understood cancers, with no established therapeutic guidelines. We conducted a national retrospective study of MH diagnosed in France between 2000 and 2023. All cases underwent centralized histological review, and several malignant tumors with a stroma highly enriched in histiocytes were excluded. In total, 141 patients were included, with a median age of 62 years (range, 1-87). The cases comprised either primary MH (64%) or MH associated with other hematologic malignancies (36%). Phenotypes corresponded to histiocytic (43%), interdigita

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… CHOP, cyclophosphamide-doxorubicin-vincristine-prednisolone; ICE, ifosfamide-carboplatin-etoposide; ref, reference; TOTEM, topotecan-temozolomide. OS and associated factors The median follow-up of our cohort was 58.2 months (95% confidence interval [CI], 33.2-79.0). … Our series only includes 18 children; however, it also provides some interesting data: (1) prognosis of MH secondary to ALL is unfavorable; and (2) the persistent CR of 2 children after topotecan-temozolomide, which includes temozolomide and topotecan, contrasts with the poor responses to other chemotherapies …

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Protein quality control allows eukaryotes to maintain proteostasis under the stress of constantly changing conditions. In this review, we discuss the current literature on PQC, highlighting flaws that must exist for malignancy to occur. At the nidus of PQC, the expression of BAG1-6 reflects the cell environment; each isoform directs proteins toward different, parallel branches of the quality control cascade. The sum of these branches creates a net shift toward either homeostasis or apoptosis. With an established role in ALP, Bag3 is necessary for cell survival in stress conditions including th

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… The optimal treatment consists in surgical resection, typically at the time of biopsy, followed by concomitant radiation/chemotherapy and adjuvant therapy with temozolomide ± bevacizumab [ 33 ]. … Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs. Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial JAMA 2017 318 2306 2316 Erratum in JAMA 2018 , 319 , 1824 10.1001/jama.2017.18718 29260225 PMC5820703 34. Ou A. Yung W.K.A. …

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

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… Sravya et al . [ 41 ] investigated the development of temozolomide resistance and found that mtDNA-depleted GBM cell lines exhibit-ed reduced sensitivity to radiation and temozolomide treatment. … GBM cells exhibit resistance to temozolomide by engaging the BER pathway to repair cytotoxic lesions such as 3-methyl-adenine (3-meA) and abasic sites. …

The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.

Glioblastoma is the most common and aggressive brain tumour in adults, and despite ongoing efforts, effective treatment remains limited. Standard therapies often face challenges because of the tumour's specific biology, its aggressive nature, and the presence of certain physiological barriers in the brain that impede chemotherapeutics from reaching their target. Emerging research in circadian biology highlights the role of the internal circadian clock in tumour progression and treatment response. Evidence suggests that aligning therapy to patients' chronotypes could potentially improve treatme

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… Correlation between levels of clock protein expression and effects on temozolomide-resistant glioblastoma and tumor progression. Hum. Cell. 2025;38:75. doi: 10.1007/s13577-025-01205-y. 67. … Circadian variation in MGMT promoter methylation and expression predicts sensitivity to temozolomide in glioblastoma. J. Neuro-Oncol. 2025;176:36. doi: 10.1007/s11060-025-05242-3. 84. …

Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy.

Dendritic cells (DCs) are antigen-presenting cells (APCs) that are essential for the activation of immune responses. In various malignancies, these immunostimulatory properties are exploited by DC-therapy, aiming at the induction of effective anti-tumor immunity by vaccination with ex vivo antigen-loaded DCs. Depending on the type of DC-therapy used, long-term clinical efficacy upon DC-therapy remains restricted to a proportion of patients, likely due to lack of immunogenicity of tumor cells, presence of a stromal compartment, and the suppressive tumor microenvironment (TME), thereby leading t

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… In addition, cyclophosphamide and temozolomide deplete Tregs and induce lymphoablation upon treatment with low-dose or high-dose, respectively. Immunological functions of gemcitabine entail depletion of Tregs and MDSCs. … Temozolomide The alkylating agent temozolomide (TMZ) induces lymphoablation upon high doses whereas at low doses it primarily targets Tregs (Figure 1 ) ( 49 ). …