ArticleBritish journal of clinical pharmacology2015
Pharmacodynamics and pharmacokinetics of oral topotecan in patients with advanced solid tumours and impaired renal function.
Article in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- Population Pharmacokinetics of Oral Topotecan in Infants and Very Young Children with Brain Tumors Demonstrates a Role of ABCG2 rs4148157 on the Absorption Rate Constant.Drug metabolism and disposition: the biological fate of chemicals · 2016Trial
- Camptothecin in Cancer Therapy: Current Challenges and Emerging Strategies with Nanoemulsions.Pharmaceutics · 2025Review
- Heterocyclic Phytochemicals as Anticancer Agents.Current topics in medicinal chemistry · 2025Review
- Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.International journal of molecular sciences · 2023Review
- Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
13 authors at 10 institutions in 3 countries.
Funding
Abstract
aimsThe aim of the study was to determine the effect of renal impairment and prior platinum-based chemotherapy on the toxicity and pharmacokinetics of oral topotecan and to identify recommended doses for patients with renal impairment or prior platinum-based (PB) chemotherapy.
methodsA multicentre phase I toxicity and pharmacokinetic study of oral topotecan was conducted in patients with advanced solid tumours. Patients were grouped by normal renal function with limited or prior PB chemotherapy or impaired renal function (mild [creatinine clearance (CLcr) = 50-79 ml min(-1) ], moderate [CLcr = 30-49 ml min(-1) ], severe [CLcr <30 ml min(-1) ]).
resultsFifty-nine patients were evaluable. Topotecan lactone and total topotecan area under the concentration-time curve (AUC) was significantly increased in patients with moderate and severe renal impairment (109% and 174%, respectively, topotecan lactone and 148% and 298%, respectively, total topotecan). Asian patients (23 in total) had higher AUCs than non-Asian patients with the same degree of renal impairment. Thirteen dose-limiting toxicities (DLTs) were observed, which were mostly haematological. The maximum tolerated dose (MTD) was 2.3 mg m(-2) day(-1) , given on days 1 to 5 in a 21 day cycle, for patients with prior PB chemotherapy or mild renal impairment, and 1.2 mg m(-2) day(-1) for patients with moderate renal impairment (suggested dose 1.9 mg m(-2) day(-1) for non-Asians). Due to incomplete enrolment of patients with severe renal impairment, the MTD was determined as ≥ 0.6 mg m(-2) day(-1) in this cohort.
conclusionsOral topotecan dose adjustments are not required in patients with prior PB chemotherapy or mildly impaired renal function, but reduced doses are required for patients with moderate or severe renal impairment.
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