Abstract
Objective
To determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dosage of oral topotecan when administered in an intermittent schedule.
Study design
Phase I study.
Patients and methods
Patients received a fixed dose of oral topotecan daily for 5 of 7 days for 2 or 3 consecutive weeks followed by 1 week of rest (21- or 28-day cycles, respectively). Patients were accrued at seven different dosage levels of topotecan ranging from 1.25 to 3.0 mg/day.
Results
Fifty-five patients received a total of 153 cycles of therapy. Dose-limiting toxicities consisted of neutropenia, thrombocytopenia, and diarrhea and appeared to correlate with patient characteristics associated with low topotecan clearance, such as impaired renal function, low bodyweight, and decreased performance status. Three partial responses were reported in patients with lung cancer (non-small cell in two patients and small cell in one patient).
Conclusions
The recommended dosage for further phase II testing is 2.0 mg/day for 5 of 7 days for 2 weeks in patients with impaired renal function (calculated creatinine clearance ≤70 mL/min) and 2.5 mg/day for 5 of 7 days for 2 weeks in patients with normal renal function (calculated creatinine clearance >70 mL/min). Treatment cycles should be repeated every 21 days.
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Acknowledgment
This research was supported by a grant from GlaxoSmithKline and was presented in part at the American Society of Clinical Oncology 36th Annual Meeting, New Orleans, Louisiana, USA, May 20–23, 2000 (abstract #776). The authors have no conflicts of interest that are directly relevant to the content of this study.
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Jones, S.F., Kuhn, J.G., Greco, F.A. et al. Prolonged intermittent oral topotecan in patients with refractory and/or advanced malignancies. Am J Cancer 3, 317–324 (2004). https://doi.org/10.2165/00024669-200403050-00005
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DOI: https://doi.org/10.2165/00024669-200403050-00005