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

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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.

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Acknowledgments

This study was supported in part by Department of Health and Human Services grant P30-133330.

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Authors and Affiliations

  1. Department of Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center, 1825 Eastchester Road Rm#: 2S-50, Bronx, NY, 10461, USA

    Lakshmi Rajdev & Joseph A. Sparano

  2. Department of Epidemiology and Population Health, Division of Biostatics, Albert Einstein College of Medicine and Cancer Center, Bronx, NY, USA

    Abdissa Negassa

  3. Department of Medical Oncology, Staten Island University Hospital, 256 Mason Avenue Bldg C, Staten Island, NY, 10305, USA

    Qun Dai

  4. Department of Obstetrics, Gynecology, and Women’s Health, Division of Gynecologic Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center, Bronx, NY, USA

    Gary Goldberg & Joseph A. Sparano

  5. Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

    Kathy Miller

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  1. Lakshmi Rajdev
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  2. Abdissa Negassa
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  3. Qun Dai
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  4. Gary Goldberg
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  5. Kathy Miller
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  6. Joseph A. Sparano
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Correspondence to Lakshmi Rajdev.

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Rajdev, L., Negassa, A., Dai, Q. et al. Phase I trial of metronomic oral vinorelbine in patients with advanced cancer. Cancer Chemother Pharmacol 68, 1119–1124 (2011). https://doi.org/10.1007/s00280-011-1580-5

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  • DOI: https://doi.org/10.1007/s00280-011-1580-5

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