Original Article

Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 5, pp 1119-1124

First online:

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

  • Lakshmi RajdevAffiliated withDepartment of Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center Email author 
  • , Abdissa NegassaAffiliated withDepartment of Epidemiology and Population Health, Division of Biostatics, Albert Einstein College of Medicine and Cancer Center
  • , Qun DaiAffiliated withDepartment of Medical Oncology, Staten Island University Hospital
  • , Gary GoldbergAffiliated withDepartment of Obstetrics, Gynecology, and Women’s Health, Division of Gynecologic Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center
  • , Kathy MillerAffiliated withDepartment of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine
  • , Joseph A. SparanoAffiliated withDepartment of Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical CenterDepartment of Obstetrics, Gynecology, and Women’s Health, Division of Gynecologic Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center

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Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Keywords

Metronomic Oral Vinorelbine Advanced cancer