Phase I study of rubitecan and gemcitabine in patients with advanced malignancies
2002; Elsevier BV; Volume: 13; Issue: 11 Linguagem: Inglês
10.1093/annonc/mdf342
ISSN1569-8041
AutoresPaula M. Fracasso, Janet S. Rader, Ramaswamy Govindan, Thomas J. Herzog, Matthew A. Arquette, Alex E. Denes, David G. Mutch, Joel Picus, Benjamin Tan, Carole L. Fears, Sherry A. Goodner, Show-Li Sun,
Tópico(s)Lung Cancer Research Studies
ResumoBackgroundRubitecan (9-nitrocamptothecin, 9-NC, Orathecin™) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies.Patients and methodsTwenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m2/day administered orally on days 1–5 and 8–12 in combination with gemcitabine 1000 mg/m2 administered intravenously on days 1 and 8 of a 21-day cycle.ResultsThe MTD was defined as rubitecan 1 mg/m2 administered orally days 1–5 and 8–12, and gemcitabine 1000 mg/m2 administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients.ConclusionsThe recommended phase II dose is rubitecan 1 mg/m2 given orally on days 1–5 and 8–12 in combination with gemcitabine 1000 mg/m2 as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.
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