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Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non-Small-Cell Lung Cancer

Journal Article · · International Journal of Radiation Oncology, Biology and Physics
 [1];  [1];  [2];  [3]; ;  [1];  [4];  [1];  [4];  [5];  [4];  [6];  [4]
  1. Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada)
  2. Department of Radiation Oncology, Ottawa Regional Cancer Centre, Ottowa, ON (Canada)
  3. Department of Medical Oncology, Ottawa Regional Cancer Centre, Ottawa, ON (Canada)
  4. Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada)
  5. Department of Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada)
  6. Eli Lilly Canada, Toronto, ON (Canada)
Purpose: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m{sup 2} on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m{sup 2} Days 1-3 for Dose Levels 1-3; 20 mg/m{sup 2} Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m{sup 2}, 75 mg/m{sup 2}) 21 days apart, after concurrent therapy. Results: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. Conclusions: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.
OSTI ID:
21491696
Journal Information:
International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 79; ISSN IOBPD3; ISSN 0360-3016
Country of Publication:
United States
Language:
English

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