Phase I/II trial of weekly docetaxel and carboplatin in previously untreated patients with advanced non-small cell lung cancer

Abstract

7302 Background: Docetaxel (D) and Carboplatin (Cb) is an active regimen in advanced non-small cell lung cancer (NSCLC). A weekly delivery of these agents may allow for dose intense therapy with less toxicity than a standard once every 3-week regimen. We conducted a Phase I/II study to evaluate the toxicity and efficacy of D and Cb administered on a weekly basis to patients with advanced stage NSCLC. Methods: Patients with stage IIIB/IV NSCLC are eligible if no prior chemotherapy, ECOG performance status 0–1, creatinine clearance >50 ml/minute, and normal liver function. Prior radiotherapy and stable brain metastases were allowed. Phase I consisted of 4–6 patients per cohort assigned to increasing dose levels of D (20, 25, 30, 36, 43 mg/m2) and a fixed dose of Cb at AUC 2 IV on days 1, 8, and 15 every 4 weeks. Phase II consisted of D 43 mg/m2 and Cb AUC 2 IV on days 1, 8, and 15 every 4 weeks. Tumor response was assessed by non-RECIST criteria after cycles 3 and 6. Results: Between 06/1998 and 12/2003, accrual to Phase I was 26 patients and to Phase II was 20 patients. Patient characteristics are stage IIIB/IV (9/37), male/female (26/20), and median age 61 years (range 25–83 years). The median number of cycles for both Phase I and II is 3. 28 patients are evaluable for response after cycle 3: partial response 50% (intent to treat (ITT) 30.4%), stable disease 35.7% (ITT 21.7%), and progressive disease 14.6% (ITT 8.7%). After 6 cycles, 2 partial responses, 6 stable diseases, and 4 progressive diseases have been observed. Phase I and II response rates are similar. Median progression-free survival for 37 evaluable patients is 3.3 months (95% CI 2.1–5.9) and overall survival for 46 evaluable patients is 10.9 months (95% CI 6.4–15.4). No dose limiting toxicity was observed in Phase I. Phase II grade 3 toxicities include 3 diarrhea, 2 pneumonia, 1 asthenia, and 1 neutropenia. Grade 4 anemia was noted in one case. Conclusion: Docetaxel 43 mg/m2 and Carboplatin AUC 2 can be administered weekly in a safe and tolerable manner to patients with advanced stage NSCLC. Response rates and survival data are comparable to the reported literature. Phase II is continuing for larger patient accrual. No significant financial relationships to disclose.