{"entity":{"id":"topotecan","kind":"drug","name":"Topotecan","aka":[],"tldr":"Topotecan is the long-standing second-line chemotherapy for relapsed small-cell lung cancer, and now the comparator that new drugs must beat.","summary":"Topotecan is a topoisomerase-I poison that stabilises the enzyme-DNA cleavage complex so replication forks break the DNA. Approved 1996 (IV) and 2007 (oral) for relapsed SCLC after platinum, it is given on days 1 to 5 of a 21-day cycle and also has roles in ovarian and cervical cancer. Activity is modest, with ORR around 20% and median OS around 6 to 8 months, and myelosuppression is heavy: grade 4 neutropenia in 70% of patients, so weekly blood counts and dose reductions are routine. It was the control arm in DeLLphi-304, where tarlatamab beat it with OS 13.6 versus 8.3 months, and is the comparator again in IDeate-Lung02; in ATLANTIS, lurbinectedin plus doxorubicin did not outperform it. Topotecan defines the floor for relapsed small-cell lung cancer, and new agents are judged by how far they rise above it.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Topotecan","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Topotecan"},{"label":"NICE TA184: topotecan for the treatment of relapsed small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta184"}],"tags":[],"related":[],"cancers":["sclc","ovarian","cervical","extensive-stage-sclc"],"sections":[],"technologies":["topoisomerase-inhibitors","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["gsk","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["dellphi-304","atlantis","ideate-lung02","nct06828354","nct06801834","nct06459180","nct07604766","nct06496048","nct06619236","nct06128837","nct06500026","nct03709680","nct06449209","nct07099898","nct06679634","nct07145333","nct07286266","lurbinectedin-basket-sclc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Hycamtin","modality":"Cytotoxic (topoisomerase-I inhibitor)","mechanism":"Topoisomerase-I poison; stabilises the cleavage complex causing replication-associated DNA breaks.","approvals":[{"region":"US","year":1996,"indication":"Relapsed SCLC (IV)"},{"region":"US","year":2007,"indication":"Relapsed SCLC (oral)"},{"region":"England (NICE)","year":2009,"indication":"Relapsed small-cell lung cancer, oral topotecan, only where re-treatment with the first-line regimen is inappropriate and cyclophosphamide, doxorubicin and vincristine is contraindicated","note":"TA184, published 25 November 2009. It remains the only NICE recommendation for a cytotoxic drug in relapsed small-cell lung cancer."}],"mechanismSteps":["Enters cell as active lactone","Traps TOP1 on DNA","Replication fork collision produces double-strand breaks","Apoptosis in S-phase cells"],"dosing":{"route":"Intravenous or oral","schedule":"1.5 mg/m² IV days 1-5 every 21 days, or 2.3 mg/m² oral days 1-5","modifications":"Frequent dose reduction for neutropenia; renal dose adjustment","monitoring":"Weekly blood counts"},"toxicity":[{"event":"Neutropenia (grade 4)","grade3PlusPct":70},{"event":"Thrombocytopenia (grade 4)","grade3PlusPct":27},{"event":"Anaemia","anyGradePct":90},{"event":"Diarrhoea (oral)","anyGradePct":30}],"access":[],"regulatoryEvents":[]},"route":"/drugs/topotecan/","neighbours":{"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"extrapulmonary-nec","kind":"cancer","name":"Extrapulmonary neuroendocrine carcinoma","route":"/cancers/extrapulmonary-nec/"},{"id":"neuroblastoma-high-risk","kind":"cancer","name":"High-risk neuroblastoma","route":"/cancers/neuroblastoma-high-risk/"},{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","route":"/cancers/limited-stage-sclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-resistant-ovarian-cancer","kind":"cancer","name":"Platinum-resistant ovarian cancer","route":"/cancers/platinum-resistant-ovarian-cancer/"},{"id":"recurrent-metastatic-cervical-cancer","kind":"cancer","name":"Recurrent or metastatic cervical cancer","route":"/cancers/recurrent-metastatic-cervical-cancer/"},{"id":"retinoblastoma","kind":"cancer","name":"Retinoblastoma","route":"/cancers/retinoblastoma/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"company":[{"id":"gsk","kind":"company","name":"GSK","route":"/companies/gsk/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"trial":[{"id":"nct06500026","kind":"trial","name":"A Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer(PANKU-Lung03)","route":"/trials/nct06500026/"},{"id":"nct07099898","kind":"trial","name":"A Study of GSK5764227 in Participants With Relapsed Small Cell Lung Cancer (SCLC)","route":"/trials/nct07099898/"},{"id":"nct06828354","kind":"trial","name":"A Study of SHR-A1811 in Subjects With Ovarian Cancer","route":"/trials/nct06828354/"},{"id":"nct06459180","kind":"trial","name":"A Study to Compare Sacituzumab Tirumotecan (MK-2870) Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With","route":"/trials/nct06459180/"},{"id":"nct07286266","kind":"trial","name":"A Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer (BEHOLD-Ovarian01)","route":"/trials/nct07286266/"},{"id":"nct07604766","kind":"trial","name":"An Extension Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Can","route":"/trials/nct07604766/"},{"id":"anbl0531","kind":"trial","name":"ANBL0531","route":"/trials/anbl0531/"},{"id":"anbl17p1","kind":"trial","name":"ANBL17P1","route":"/trials/anbl17p1/"},{"id":"atlantis","kind":"trial","name":"ATLANTIS","route":"/trials/atlantis/"},{"id":"aurelia","kind":"trial","name":"AURELIA","route":"/trials/aurelia/"},{"id":"dellphi-304","kind":"trial","name":"DeLLphi-304","route":"/trials/dellphi-304/"},{"id":"ideate-lung02","kind":"trial","name":"IDeate-Lung02","route":"/trials/ideate-lung02/"},{"id":"nct06581380","kind":"trial","name":"JK-1201I Compared with Topotecan in Patients with Relapsed Extensive Stage Small Cell Lung Cancer","route":"/trials/nct06581380/"},{"id":"lurbinectedin-basket-sclc","kind":"trial","name":"Lurbinectedin basket trial, small-cell lung cancer cohort","route":"/trials/lurbinectedin-basket-sclc/"},{"id":"nct06496048","kind":"trial","name":"Lurbinectedin or in Combination with Irinotecan Versus Topotecan in Patients with Relapsed SCLC","route":"/trials/nct06496048/"},{"id":"nct07106528","kind":"trial","name":"Organoid-guided vs Topotecan Therapy in Relapsed Extensive-Stage Small Cell Lung Cancer","route":"/trials/nct07106528/"},{"id":"nct07145333","kind":"trial","name":"Pharmacogenomics ANDA SNP Clinical Study - Topotecan and Single Nucleotide Polymorphisms","route":"/trials/nct07145333/"},{"id":"nct05870748","kind":"trial","name":"REFRaME-O1: A Study to Investigate the Efficacy and Safety of Luveltamab Tazevibulin Versus Investigator's Choice (IC) Chemotherapy in Women With Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) Expressing FOLR1","route":"/trials/nct05870748/"},{"id":"nct06679634","kind":"trial","name":"Retinoblastoma Phase II Expanded Access Clinical Trial","route":"/trials/nct06679634/"},{"id":"nct06449209","kind":"trial","name":"Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy","route":"/trials/nct06449209/"},{"id":"nct03061812","kind":"trial","name":"Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)","route":"/trials/nct03061812/"},{"id":"nct06128837","kind":"trial","name":"Study of LY01610 in Patients With Recurrent Small Cell Lung Cancer","route":"/trials/nct06128837/"},{"id":"nct03709680","kind":"trial","name":"Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors","route":"/trials/nct03709680/"},{"id":"nct06801834","kind":"trial","name":"Study of Sacituzumab Govitecan Versus Standard of Care in Participants With Previously Treated Extensive Stage Small Cell Lung Cancer","route":"/trials/nct06801834/"},{"id":"nct06619236","kind":"trial","name":"Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer","route":"/trials/nct06619236/"}],"term":[{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"}],"target":[{"id":"top1","kind":"target","name":"Topoisomerase I (TOP1)","route":"/targets/top1/"}],"drug":[{"id":"trilaciclib","kind":"drug","name":"Trilaciclib","route":"/drugs/trilaciclib/"}],"pathway":[{"id":"dna-replication-licensing","kind":"pathway","name":"DNA replication & origin licensing","route":"/pathways/dna-replication-licensing/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"}]}}