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Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial.

BACKGROUND: Immunotherapy with the chimeric anti-GD2 monoclonal antibody dinutuximab, combined with alternating granulocyte-macrophage colon … tion regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide, with or without topotecan, vincristine, and doxorubicin), had achieved a disease response that fulfilled prespecified criteria, had received high-dose therapy (busulfan and melphalan or carboplatin, etoposide, and melphalan) and had received radiotherapy to the primary tumou …

Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma.

BACKGROUND: Podoplanin, a mucin-type transmembrane glycoprotein, is thought to be one of the cancer stem cell markers for squamous-cell carcinoma of the vulva. The objectives of the present study were to examine the role of podoplanin in esophageal squamous-cell carcinoma (ESCC). METHODS: Expression of podoplanin was examined immunohistochemically in 61 cases of ESCC that had not been treated with chemotherapy or radiotherapy before surgery. Because cancer stem-cell quantities have been reported to increase with chemotherapy and radiotherapy, cases in patients who did not receive such prior t

Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children.

In a retrospective analysis of 24 children with refractory or multiply relapsed acute lymphoblastic leukemia (ALL), a salvage regimen comprising amsacrine, etoposide, and high-dose methylprednisolone AEP achieved a significant treatment response in 11 of 19 evaluable patients (8 complete and 3 partial remissions). Five of 9 AEP-responsive patients who underwent subsequent stem cell transplantation are alive (median follow-up: 43 months; range 10 to 91). The load of minimal residual disease prior to transplantation appears to be predictive for outcome in this very poor-prognosis subgroup of ALL

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the eighth most common cancer in women and it is usually diagnosed at an advanced stage. The majority of ovari … gents were associated with significantly better survival or severe adverse-event profiles than PLD. Topotecan and gemcitabine were associated with significantly more haematological severe adverse events than PLD, and patupilone was associated with significantly more severe neuropathies and diarrhoea. Severe hand-foot syndrome (HFS) occurred consistently mor …

Non-conventional dosing of oral anticancer agents in oncology and malignant haematology: a systematic review protocol.

BackgroundRecent advances in cancer therapeutics have resulted in significantly improved overall survival and progression-free survival for patients. Targeted oral systemic anticancer therapies (SACT) offer a range of treatment approaches that differ from traditional cytotoxic chemotherapy: non-cytotoxic oral SACT target malignant disease continuously, have less broad and more favourable safety profiles, which can improve patients' quality of life (QoL). Toxicities associated with daily oral SACT administration can, however, result in non-adherence and a reduced QoL. Non-conventional dosing of

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… Topotecan/ 19. treosulfan.mp. 20. Tretinoin/ 21. Trifluridine/ 22. vinorelbine.mp. 23. afatinib.mp. 24. axitinib.mp. 25. bosutinib.mp. 26. cabozantinib.mp. 27. cobimetinib.mp. 28. crizotinib.mp. 29. ceritinib.mp. 30. dabrafenib.mp. 31. Dasatinib/ 32. Erlotinib Hydrochloride/ 33. … Topotecan/ 19. treosulfan.mp. 20. Tretinoin/ 21. Trifluridine/ 22. vinorelbine.mp. 23. afatinib.mp. 24. axitinib.mp. 25. bosutinib.mp. 26. cabozantinib.mp. 27. cobimetinib.mp. 28. crizotinib.mp. 29. ceritinib.mp. 30. dabrafenib.mp. 31. Dasatinib/ 32. Erlotinib Hydrochloride/ 33. …

Therapies and nanotherapies for cervical cancer (Review).

Cervical cancer (CC) is a major global health concern, ranking fourth worldwide in mortality, due to its high death rate and strong link to persistent high-risk human papillomavirus infections, which drive cancer progression through cellular dysregulation. Conventional therapies used in the treatment of CC have significant disadvantages, such as adverse side effects that affect the quality of life of patients. These side effects may include nausea, vomiting, fatigue, hair loss, fertility problems, damage to nearby organs and systemic toxicity. To address these challenges, there has been an inc

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… This image illustrates the effects of various drugs and genetic silencers used in cervical cancer therapy, including (A) cisplatin, (B) topotecan, (C) pazopanib and (D) dsRNA. … The combination of cisplatin and topotecan as a second-line treatment for patients with advanced/recurrent uterine cervix cancer. Medicine (Baltimore) 2018;97(e0340) doi: 10.1097/MD.0000000000010340. 31. …

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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… Thalidomide with standard topotecan resulted in 2 months' increase in PFS in a different phase II trial [ 155 ]. … Metronomic topotecan was combined with pazopanib and tested against human RCC cell lines. The combination induced and maintained dormancy in metastatic foci. Pazopanib was also shown to increase intracellular topotecan levels [ 171 ]. …

The impact of Pegylated liposomal doxorubicin in recurrent ovarian cancer: an updated meta-analysis of randomized clinical trials.

BackgroundPrevious meta-analysis studies suggested that pegylated liposomal doxorubicin (PLD) may improve the survival rate of patients with recurrent ovarian cancer. The aim of the present meta-analysis, then, was to further update the role of PLD in the treatment of recurrent ovarian cancer.MethodsWe performed a literature search using the electronic databases Medicine, EMBASE, Web of Science, and the Cochrane Library to 27 July 2020. We only restricted the randomized clinical trials. Study-specific hazard ratios and 95% confidence interval (HR/95% CI) and risk ratios and 95% confidence inte

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… Vergote 2009 [ 18 ] was utilized in both trials—PLD vs topotecan and PLD vs canfosfamide, and Kaye 2012 [ 21 ] was integrated into both trials—PLD vs. 200 mg of olaparib and PLD vs. 400 mg of olaparib. All features of the included studies are depicted in Table. 1 . … or PLD | Toxicity | | Canfosfamide 1000 mg/m2 q3wks | 231 | 60 (26–85) | | Vergote2009II [ 19 ] | PLD 50 mg/m2 IVI q4wks | 130 | 60 (30–82) | phase III randomized multicenter | platinum-refractory or PR ROC | Failed one second-Line therapy with either topotecan or PLD | Toxicity | | Topotecan …

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of

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… In the TAHOE study, the median OS was 6.3 months in the Rova-T arm and 8.6 months in the topotecan arm [ 6 ]. … (8.6 months); ORR: Rova-T (15%) vs topotecan (21%) [ 6 ] Phase 3 MERU: OS: Rova-T (8.8 months) vs topotecan (9.9 months); ORR: Rova-T (9%) vs topotecan (4%) [ 35 ] SC-002 | Unknown/not published | Administered to 35 patients with relapsed/refractory SCLC in an FIH study [ 113 ] Study terminated with …

New developments in immunotherapy for SCLC.

Small cell lung cancer (SCLC) is an aggressive form of neuroendocrine neoplasm known for its striking initial response to treatment, followed by fast relapse and refractoriness in response to additional lines of therapy. New advances in immunotherapy are paving the way for more effective treatment strategies and have promising results with early clinical trial data. While SCLC rarely harbors actionable mutations, the receptor DLL3 is extensively present in SCLC, making it a potential target for immunotherapy. Three emerging therapeutic options include bispecific T cell engagers targeting DLL3,

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… On relapse, subsequent lines of therapy can include rechallenge with platinum-based therapy (if initial response is at least 90 days or more), lurbinectedin, or irinotecan/topotecan, among others. Lurbinectedin was introduced as safe and active second-line treatment for SCLC. … Unfortunately, progression-free survival was similar in both arms of the study, showing no benefit from the addition of tiragolumab. 14 Similarly, the combination of ATR inhibitor with topotecan did not improve progression-free survival in relapsed/refractory SCLC and resulted in an improvement in OS …

PARP Inhibitors and Haematological Malignancies-Friend or Foe?

Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite promising results in vitro, few clinical trials in humans for haematological malignancies have been performed, and additional investigation is

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… Olaparib sensitised cells to treatment with 4HC, fludarabine, valproic acid, bendamustine and irradiation | + | ++ | [ 73 ] Patient samples | Talazoparib | - | Induced cell death | + | N/A | [ 74 ] NHL | Granta-519, Jeko1, JVM2, Z138C | AG14361 | Topotecan | AG14361 potentiated topotecan cytotoxicity … i.v. topotecan days 1–5 ( n = 3); Cohort 4: −3: 10 mg po BID veliparib days 2–5 (cycle 1) and days 1–5 (cycle 2 onwards) + 0.6 mg/m 2 /d i.v. topotecan days 1–5 ( n = 4 + 3); Cohort 5: 10 mg po BID veliparib day 1 + 0.75 mg/m 2 /d i.v. topotecan days 1–5 ( n = 5) | Most common DLTs: grade 4 neutropaenia …

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

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… In addition to retinoblastoma, also neuroblastoma might be potentially treatable with vincristine and topotecan co-administered with doxorubicin. … Also, cyclophosphamide is a suitable drug to be combined with vincristine and topotecan. …

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

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… Topotecan Topotecan ( Table 5 ) selectively inhibits topoisomerase I, which catalyses single-strand DNA cleavage. Topotecan binds to the enzyme and prevents the re-ligation step, causing the formation of a single-strand DNA gap and simultaneously trapping the enzyme [ 129 ]. … Topotecan is used as part of second-line therapy for metastatic ovarian cancers and relapsed small cell lung cancers. …

Kinase Inhibitors and Ovarian Cancer.

Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a

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… Similar results were reported when patients with advanced/or recurrent gynecologic malignancies were treated with temsirolimus and topotecan (a topoisomerase inhibitor). … Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018;19:1247–1258. doi: 10.1016/S1470-2045(18)30372-3. 30. …

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

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… Topotecan and irinotecan are well-established topoisomerase 1 (Top1) poisons used against many cancer types. … In particular, it has been found that the adjunctive administration of TDP1 inhibitor with topotecan substantially reduces metastasis growth in Lewis lung carcinoma models, making TDP1 a very promising therapeutic target [ 13 ]. 8. …

Treatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue.

Treatment of aggressive lymphoma in relapse is difficult. Patients who initially present with these diseases often know they have a malignan … omplete response less than 1 year. Finally, we have recently studied paclitaxel in combination with topotecan for relapsed and refractory aggressive lymphomas. These and newer combinations should be further developed to treat patients in relapse of aggressive lymphomas.

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 …

Lack of correlation between the costs of anticancer drugs and clinical benefits in Japan.

Both overall survival (OS) and progression-free survival (PFS) are primary endpoints of phase III studies of new anticancer drugs. Medical care expenditures, especially oncology drug prices, are rapidly increasing; however, the impact of oncology drug prices on OS and PFS is unclear. We analyzed the relationship between oncology drug prices and clinical outcomes in Japan. The costs of a full course or 1 year of treatment were estimated on the basis of the latest National Health Insurance Drug Price Standards, and the relationship between costs and improvements in OS or PFS obtained with each d

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… The lowest CI OS was ¥3950 for topotecan in ovarian cancer, and the highest CI OS was ¥141 929 for vemurafenib in malignant melanoma, which was 35.93‐fold more expensive than the cost of topotecan required to prolong OS by 1 day (Table 1 ). … GC | 56 901 | | | Regorafenib | CRC | 21 325 | | | Temozolomid | MalGli | 24 814 | | | Gemcitabine | BC | 12 517 | | | Pemetrexed | MalMeso | 39 441 | | | Doxorubicin HCl liposome (Doxil®) c | OC | 120 580 | | | Cabazitaxel | PrC | 23 361 | | | Docetaxel | PrC | 12 581 | | | Topotecan …

Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM).

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… This approach has changed in recent years as a number of cytotoxic drugs such as capecitabine, vinorelbine, or topotecan have become available as oral agents for the treatment of a large variety of tumors like colon, breast, gastric, ovarian, or lung cancer ( Table 1 ). … November 2007 | Chronic myelogenous leukemia Sorafenib | July 2006 | Hepatocellular carcinoma, renal cell carcinoma Sunitinib | July 2006 | Malignant gastrointestinal stromal tumor, renal cell carcinoma Thalidomide | April 2008 | Multiple myeloma Vinorelbine | April 2004 | Breast cancer, lung cancer Topotecan …

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and abs

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… In breast cancer cells (MCF-7), oncogenic miR-21 was involved in topotecan-resistance and downregulation of miR-21 re-sensitized breast cancer cells to topotecan [74] . … Three microRNAs (miR-34b, miR-431, miR-518c-AS) were upregulated by topotecan treatment, while miR-142-5p was downregulated by topotecan in drug resistant ovarian cancer cells [75] . Fig. 4 Chemical structures of camptothecin derivatives and trabectedin. …