ArticleBritish journal of cancer2015
Phase I and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.Frontiers in oncology · 2024Review
- Recent advances on anti-angiogenic multi-receptor tyrosine kinase inhibitors in osteosarcoma and Ewing sarcoma.Frontiers in oncology · 2023Review
- Article
- Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.Signal transduction and targeted therapy · 2020Review
- Cancer Stem Cells in Soft-Tissue Sarcomas.Cells · 2020Review
- Revisiting the role of ABC transporters in multidrug-resistant cancer.Nature reviews. Cancer · 2018Review
- Anti-angiogenesis target therapy for advanced osteosarcoma (Review).Oncology reports · 2017Review
- Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect.Nature reviews. Clinical oncology · 2016Review
- Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma.Clinical sarcoma research · 2016Review
- Combination metronomic oral topotecan and pazopanib: a pharmacokinetic study in patients with gynecological cancer.Anticancer research · 2013Article
- Combination of metronomic oral pazopanib and topotecan for recurrent glioblastoma with and without previous bevacizumab: Results from a phase 2 clinical trial.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral topotecan in combination with pazopanib in patients with advanced solid tumours.
methodsStage I of this study was to determine whether there was an impact of pazopanib on topotecan exposure. In stage II, the MTD and safety profile of oral topotecan given weekly on days 1, 8 and 15 in a 28-day cycle; or daily-times-five on days 1-5 in a 21-day cycle, both in combination with daily pazopanib, were explored.
resultsIn total, 67 patients were enroled. Pazopanib co-administration caused a substantial increase in exposure to total topotecan (1.7-fold) compared with topotecan alone, which is considered clinically relevant. Topotecan had no effect on pazopanib concentrations. Safety findings were consistent with the known profile of both agents. There were three drug-related deaths, liver failure, tumour haemorrhage and myelosuppression. Two patients experienced dose-limiting toxicities (DLTs; hand-foot syndrome, myelosuppression and diarrhoea) on the weekly topotecan schedule and four patients experienced DLTs (myelosuppression) on the daily-times-five topotecan schedule. When combined with pazopanib, 800 mg daily, the recommended doses for oral topotecan are: 8 mg weekly and 2.5 mg daily-times-five. Seven of eight patients with partial response had platinum-resistant ovarian cancer. In addition, 54% of patients had stable disease with 22% stable for 6 months.
conclusionsTotal topotecan exposure is 1.7-fold higher when co-administered with pazopanib. Both schedules of administration were tolerated and would permit further evaluation, especially the weekly schedule.
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