Abstract
Background
Oxaliplatin and topotecan are novel options for a variety of neoplasms. Topotecan has shown fewer side effects and higher efficacy when given as a continuous i.v. infusion compared to single doses, but this regimen has not yet been combined with oxaliplatin.
Patients and methods
This phase I/II trial was designed to establish the dose-limiting toxicity of a combination of oxaliplatin (85–130 mg/m2 on day 1) and a continuous infusion of topotecan (initial 0.9 mg/m2 over 72–120 h). Eligible patients with metastatic colorectal cancer had progressive disease during, or within 12 weeks after, palliative fluoropyrimidine-based chemotherapy or in whom intolerable 5-FU toxicity had developed.
Results
The study included 21 patients. Subjectively the treatment was well tolerated but haematological toxicity was observed with the initial treatment schedule of oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 on days 1–5. Reducing topotecan to 0.9 mg/m2 on days 1–3 resulted also in acceptable haematological toxicity. In patients completing three or more therapy cycles, median progression-free survival was 5 months, and 50% had stable disease or showed a partial response.
Conclusion
The recommended dose of this combination for further testing is oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 per day as a continuous infusion on days 1–3.
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Dr. Hubert Szélenyi, born 11 January 1965, died in the prime of life on 29 August 2002. We are deeply saddened by the loss of an excellent physician, accomplished scientist and admirable and warm-hearted friend and colleague. He had essentially designed and developed this study, and we decided to finish it in compliance with his intentions.
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Hütter, G., Szélenyi, H., Deckert, P.M. et al. Phase I/II trial of topotecan given as continuous infusion in combination with oxaliplatin in 5-FU-pretreated patients with colorectal cancer. Cancer Chemother Pharmacol 54, 178–184 (2004). https://doi.org/10.1007/s00280-004-0796-z
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DOI: https://doi.org/10.1007/s00280-004-0796-z