P2-250: A Phase II Study of Gleevec (Imatinib Mesylate) Plus Taxotere (Docetaxel) in Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Docetaxel has been shown to improve overall survival in patients with recurrent NSCLC. Pre-clinical data suggests synergistic activity with the combination of docetaxel and imatinib. Paul Matthew, et al demonstrated the safety of this combination in the MD Anderson trial “Targeting the platelet-derived growth factor receptor in androgen-independent prostate cancer.” Therefore this combination was administered to patients with recurrent NSCLC to determine overall response rate. This is a phase II study of the combination of Taxotere and Gleevec in refractory NSCLC to determine tumor activity, toxicity and recommendations for further studies of this combination. Patients must have received at least one prior regimen and experienced recurrence or have been refractory to the initial treatment. Taxotere was administered at 30 mg/M2 on a weekly schedule for 3 weeks followed by one week rest. Gleevec was administered at a starting dose of 600 mg daily. Dose modifications to address toxicity were built in to the protocol. To date, a total of 10 patients have been enrolled on this study. Seven male and 3 female with a median age of 66 years (range 58 - 74). A total of 26 cycles were delivered to 10 patients (mean = 3). Four patients experienced fatal adverse events while on study. Two with a non-study related fatal MI (both with history of heart disease). One patient developed GI perforation not related to study (history of ischemic bowel disease). One patient suffered a fatal pulmonary embolus not related to study (history of CAD and peripheral vascular disease). Grade 4 toxicities included periorbital edema (1 pt), pneumonia (2 pts), diarrhea (1 pt), dehydration (1 pt), dyspnea (1pt), anorexia (1 pt), bilateral pleural effusion (1 pt), and neutropenia (2 pts). Grade 3 toxicities included hyponatremia, renal failure, hypotension, mental status changes, anorexia, azotemia, dyspnea, herpetic esophageal ulcer, pneumonia, cough, neutropenia, shortness of breath, weakness, fatigue, and anemia. Responses were minimal. Four of 10 patients received only 1 cycle. Three of those 4 suffered a fatal adverse event and tumor assessment was not performed. The fourth developed herpetic esophageal lesions and was started on 2nd line therapy prior to tumor assessment. One patient had stable disease after 2 cycles but progressed after cycle 3. One patient received 3 cycles, had stable disease after cycle 2 but refused additional therapy after cycle 3 due to grade 2 nausea. One patient had stable disease after 6 cycles then experienced a fatal pulmonary embolus. An additional patient had a partial response after cycle 4 but CT after cycle 6 demonstrated progression. Two patients progressed after cycle 2.