Phase I trial of metronomic oral vinorelbine in patients with advanced cancer

• DOI: 10.1007/s00280-011-1580-5
• Publication Date: 2011-03-05T03:36:53Z
• Authors: Lakshmi Rajdev; Abdissa Negassa; Qun Dai; Gary Goldberg; Kathy Miller; Joseph A. Sparano
• Keywords: Adult; Male; 0301 basic medicine; Maximum Tolerated Dose; Administration, Oral; Vinorelbine; Middle Aged; Vinblastine; Antineoplastic Agents, Phytogenic; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Neoplasms; Humans; Female; Aged

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.