A phase II study of docetaxel (D) plus imatinib (I) in patients with previously treated non-small cell lung cancer

Abstract

18200 Background: Docetaxel(D) has been shown to improve overall survival in pts with previously treated NSCLC. Pre-clinical data suggest synergistic activity with the combination of D and I. Paul Matthew; et al demonstrated the safety of this combination in pts with prostate cancer. Methods: This is a Phase II study of the combination of D and I in prev tx NSCLC to determine response rate, toxicity and assess overall survival. Pts must have received at least 1 prior regimen and have an ECOG PS of 2 or less. Prior tx with D was allowed. D was admin at 30 mg/m2 on a weekly schedule for 3 weeks followed by 1 week rest. I was admin at a starting dose of 600 mg/day throughout the study. Results: A total of 10 pts were enrolled. Seven male and 3 female with a median age of 66 years (range 58 - 74). A total of 26 cycles were delivered to 10 pts (mean = 3). Responses included 1 PR/3SD/2PD/4NE. One pt with a PR responded after cycle 4 but progressed after cycle 6. One pt maintained SD for 21 wks then expired due to an unrelated PE (h/o peripheral vascular disease). Grade 4 toxicity included periorbital edema (1 pt), pneumonia (2 pts), diarrhea (1 pt), dehydration (1 pt), dyspnea (1pt), anorexia (1 pt), pleural effusion (1 pt), and neutropenia (2 pts). Grade 3 toxicity included hyponatremia (1 pt), renal failure (1 pt), hypotension (2 pts), mental status changes (1 pt), anorexia (1 pt), azotemia (1 pt), dyspnea (1 pt), herpetic esophageal ulcer (1 pt), pneumonia (1 pt), neutropenia (2 pts), weakness & fatigue (1 pt), and anemia (1 pt). Four of 10 pts received only 1 cycle. (Three of those 4 suffered a fatal adverse event during cycle 1, not felt to be treatment related. The fourth developed herpetic esophageal lesions and was taken off study prior to tumor assessment.) Conclusions: The study was closed before the initial planned pts were enrolled due to low activity and unexpected high tox. Only 1 of 10 pts achieved a PR. Stable disease was observed in 3 pts but was of short duration in 2 of the 3. Despite supportive treatment, nausea, vomiting, diarrhea, and anorexia were difficult to control. Hematologic toxicity was encouragingly infrequent with only 2 pts experiencing Grade 4 neutropenia. Alternative dosing schedules would be recommended before pursuing this combination in NSCLC pts. Study supported by a grant from Novartis. No significant financial relationships to disclose.