Preclinical and Pilot Clinical Studies of Docetaxel Chemoradiation for Stage III Non-Small-Cell Lung Cancer
- Department of Medical Oncology, University of Rochester Medical Center, Rochester, NY (United States)
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY (United States)
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY (United States)
- Division of Cardiothoracic Surgery, University of Rochester Medical Center, Rochester, NY (United States)
- Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)
- Division of Cardiothoracic Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH (Lebanon)
Purpose: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT. Methods and Materials: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m{sup 2} of docetaxel and 75 mg/m{sup 2} of cisplatin on Day 1 and 150 mg/m{sup 2} of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m{sup 2} and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease. Results: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients. Conclusions: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor followed by pulsed low-dose docetaxel CRT is promising with regard to its antitumor activity, low rates of distant failure, and low toxicity, suggesting that this regimen deserves further investigation.
- OSTI ID:
- 21587634
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 80; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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