This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Okunieff, P. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Okunieff, P.

Phase I/II Clinical Study of Pulsed Paclitaxel Radiosensitization for Thoracic Malignancy

A Therapeutic Approach on the Basis of Preclinical Research of Human Cancer Cell Lines¹

Department of Radiation Oncology [Y. C., P. C. K., J. L., Y-J. L., T. S., P. O.], Medical Oncology [K. P.], and Thoracic Surgery [D. J.], James P. Wilmot Cancer Center, University of Rochester, Rochester, New York 14642

Purpose: A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignancy was conducted. The study was based on preclinical research of the effects of paclitaxel on apoptosis and the cell cycle in human cancer cell lines.

Experimental Design: Three human epithelial cancer cell lines were investigated for preclinical study. Cells were analyzed for apoptosis and cell cycle characteristics after paclitaxel treatment. The Phase I/II clinical trial for non-small cell lung cancer used pulsed low-dose paclitaxel three times/week with the starting dose of 15 mg/m². Daily thoracic radiotherapy was delivered in 1.8 Gy/fraction to 60–65 Gy for gross disease and to 45–58 Gy for microscopic disease. Timing of radiotherapy was delayed to allow for a minimum of 4 h for cell cycle progression.

Results: Forty-one patients have enrolled and 33 completed treatments. Seventeen patients completed the Phase I study, with an average primary tumor shrinkage of 83 ± 8% (95% confidence interval). Tumor response rate was 100% for the Phase I study. Overall local control was 98%, and the survival rate was 46% at 1 year, 33% at 2 years, and 18% at 3 years. Toxicity was low with 3 of 18 patients having grade 3 pneumonitis and 3 of 18 patients having grade 3 esophagitis. There was no grade 4 pneumonitis, esophagitis, or hematological toxicity.

Conclusions: Pulsed low-dose paclitaxel radiosensitization for non-small cell lung cancer resulted in a superior local control rate and comparable survival rate when compared with chemoradiation regimens using systemic dose chemotherapy. The regimen is associated with low toxicity and deserves additional investigation, particularly in patients with poor performance or older age, who cannot tolerate standard chemoradiation regimens.

This article has been cited by other articles:

				S. G. Divers, S. A. Spencer, D. Carey, E. M. Busby, M. D. Hyatt, and F. Robert Phase I/IIa Study of Cisplatin and Gemcitabine As Induction Chemotherapy Followed by Concurrent Chemoradiotherapy With Gemcitabine and Paclitaxel for Locally Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., September 20, 2005; 23(27): 6664 - 6673. [Abstract] [Full Text] [PDF]

				B. Jeremic, B. Milicic, L. Acimovic, and S. Milisavljevic Concurrent Hyperfractionated Radiotherapy and Low-Dose Daily Carboplatin and Paclitaxel in Patients With Stage III Non-Small-Cell Lung Cancer: Long-Term Results of a Phase II Study J. Clin. Oncol., February 20, 2005; 23(6): 1144 - 1151. [Abstract] [Full Text] [PDF]