Pilot Study Of Carboplatin/Radiotherapy Plus 'Dose-Dense' Pemetrexed For Locally Advanced Non-Small Cell Lung Carcinoma

7571 Background: This is a prospective Pilot/Phase I dose-seeking clinical trial of dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) and carboplatin for locally advanced non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy (conventional fractionation) with carboplatin (AUC = 6) during Weeks 1 and 5 of XRT, and pemetrexed during Weeks 1, 3, 5, and 7 of XRT. Vitamin prophylaxis (B12/folate) was started prior to treatment. The starting dose level of pemetrexed was 300 mg/m2, with plans to dose escalate after 3–6 patients had at least 30 days of evaluability post-treatment without dose-limiting toxicity (DLT). DLT was defined as any Grade 4 toxicity, selected Grade 3 toxicities (chemo-XRT pneumonopathy, esophagitis lasting > 14 days), and/or inability to complete at least 54 Gy of XRT). Consolidation carboplatin (AUC=6) and pemetrexed (500 mg/m2) q3 weeks × 2 cycles was also planned. Results: Fourteen patients were enrolled; 10 are evaluable for feasibility/toxicity; 9 are evaluable for response. All 10 patients received both doses of concurrent carboplatin; 9/10 received a full dose of XRT. Five of 10 patients received four doses of pemetrexed; the median cumulative concurrent pemetrexed dose delivered was 1,150 mg/m2. The main toxicity of concurrent chemo-XRT was neutropenia, with a median ANC nadir of 1.4; three patients had Grade ≥ 3 neutropenia. One patient had multiple Grade 4 toxicities (infection, multi-organ failure) and a 2nd patient had prolonged Grade 3 esophagitis - these were considered DLTs and the study was amended to require reduced XRT field size (involved field). No patient had Grade ≥3 chemo-XRT pneumonopathy. All patients recovered from their acute toxicities; there were no treatment-related deaths and no unusual/unexpected toxicities. In-field local tumor responses were observed in 7 of 9 evaluable patients. Conclusions: Although generally well tolerated, feasible and active, XRT/pemetrexed/carboplatin as given in the original design of Dose Level I exceeded pre-defined DLT boundaries. Study accrual continues, using involved field XRT, and updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly