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A phase 2 pilot trial of low-dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma
Article first published online: 29 JAN 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 7, pages 1751–1756, 1 April 2010
How to Cite
Bhatt, R. S., Merchan, J., Parker, R., Wu, H.-K., Zhang, L., Seery, V., Heymach, J. V., Atkins, M. B., McDermott, D. and Sukhatme, V. P. (2010), A phase 2 pilot trial of low-dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma. Cancer, 116: 1751–1756. doi: 10.1002/cncr.24902
- Issue published online: 19 MAR 2010
- Article first published online: 29 JAN 2010
- Manuscript Accepted: 17 JUL 2009
- Manuscript Revised: 13 JUL 2009
- Manuscript Received: 14 MAY 2009
- NIH. Grant Number: R21 CA097730-01A1
- Pfizer Inc.
- Clinical Investigator Training Program: Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Company
- cyclooxygenase 2;
- clinical trial;
- phase 2
Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM.
Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study.
Twenty patients were enrolled. Twelve of 20 patients (60%) had received ≥2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days).
Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society.