Phase I trial of metronomic oral vinorelbine in patients with advanced cancer
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- Rajdev, L., Negassa, A., Dai, Q. et al. Cancer Chemother Pharmacol (2011) 68: 1119. doi:10.1007/s00280-011-1580-5
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Antitubulin agents exhibit antiangiogenic effects in vitro and in vivo. We evaluated the safety and feasibility of administering a metronomic schedule of oral vinorelbine designed to optimize its antiangiogenic effects.
Patient with advanced cancer who had progressive disease after standard therapy received oral vinorelbine 3 times weekly (i.e., Monday, Wednesday, Friday) at the 6 dose levels ranging from 20 mg (1 week on, 1 week off) to 50 mg (3 weeks on, 1 week off) in cohorts of 3–6 patients at each dose level using a standard phase I design. Dose-limiting toxicity (DLT) during cycle 1 included: (1) neutrophil nadir < 500/μL attributed to therapy, (2) platelet nadir < 50,000/μL attributed to therapy, (3) grade 3–4 non-hematologic toxicity attributed to therapy, and (4) neutropenia associated with grade 2 fever (i.e., febrile neutropenia).
Nineteen patients received 50 cycles of therapy (range 1–11 cycles) at 6 dose levels. There were no dose-limiting toxic events. There were no consistent changes in serum TIE-2 or VCAM-1 levels, or urinary VEGF. One patient with renal cell carcinoma had stable disease for 9 months, and another patient with metastatic prostate cancer had a 70% decline in serum prostate-specific antigen, which lasted 4 months.
Oral vinorelbine may be given using a metronomic schedule, 50 mg thrice weekly for three of 4 weeks, with minimal toxicity in patients with advanced cancer.