Phase II trial of gemcitabine (G), carboplatin (C) and bexarotene (B) in patients (pts) with newly diagnosed, locally-advanced or metastatic non-small cell carcinoma of the lung (NSCLC)

Abstract

7308 Background: The current standard of care for unresectable NSCLC is platinum-based chemotherapy. There is no benefit to adding together 3 or more cytotoxic agents, but adding a biologic agent may improve response rates and survival. B, a retinoic acid X-receptor agonist, is a differentiating agent with antineoplastic activity. Recent data suggests that the addition of B to platinum-based therapy may increase response rates and survival in NSCLC. Due to the poor outcome in this disease, we are studying a combination of G, C, and B as front-line therapy. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV; Karnofsky PS 70–100%; age ≥ 18, adequate bone marrow, renal and hepatic function, and written informed consent. Pts receive G, 1 g/m2 days 1 and 8 with C, AUC 5 (Calvert formula) on day 8. B, 400mg/m2 PO QD in divided doses is given days 1–28 of each treatment cycle. Pts may receive up to 6 cycles of chemotherapy or 2 cycles after CR achieved. Tumor restaging is performed every 2 cycles of therapy, in the absence of obvious rapid disease progression. Results: 19 pts have been enrolled; 10 males, 9 females; median age is 63.5 years (range 30–85 years). 2 pts had protocol violations (prior chemotherapy (1); small cell cancer on further pathologic evaluation (1)). A median of 2 cycles has been delivered (range 1–6). To date, the overall PR rate is 23.5% (4/17); 2 have had SD (1 progressed by cycle 4), for an overall clinical benefit rate of 35%. One is too early to evaluate. 18 pts to date are evaluable for toxicity. Thus far, the mean TTP is 68 days, and the mean OS is 142 days. The therapy has been well-tolerated with 7 pts experiencing Grade 2–3 myelosuppression (no febrile neutropenia), and 3 pts experiencing Grade 3–4 nausea and emesis. There have been no significant B-related adverse events. Conclusions: The addition of the differentiating agent B to a regimen of G and C is tolerable and active. In contrast to other studies, our early results suggest that the addition of B at this dose and schedule may add little to the clinical benefit observed with this regimen. Accrual continues in an effort to better define response rate and duration. No significant financial relationships to disclose.