A phase I study evaluating bronchial artery infusion (BAI) of gemcitabine in recurrent or progressive non-small cell lung cancer (NSCLC).

Abstract

e13080 Background: BAI therapy in lung cancer is of interest due to several advantages over systemic chemotherapy, including delivery of a large dose of drug directly to the tumor and less systemic toxicities. Methods: Patients with recurrent or progressive NSCLC following at least 2 lines of therapy were enrolled in a phase I study evaluating BAI of gemcitabine to assess safety, pharmacokinetics and local tumor response. Patients were given BAI of gemcitabine with a dose of 600 mg/m2 on day 1 of cycle 1, followed by intravenous gemcitabine of 1,000 mg/m2 on day 8 of cycle 1 and days 1 and 8 of all subsequent cycles. Each cycle lasted 21 days. Optional gemcitabine by BAI rather than IV on day 1 of odd numbered cycles was offered. Treatment was continued until progressive disease (PD) or toxicity. Pharmacokinetics for plasma gemcitabine, dFdU, and active triphosphorylated metabolite (dFdCTP) in peripheral blood mononuclear cells were evaluated following BAI and IV infusions. Results: A total of 4 patients were recruited. One patient was discontinued after inability to cannulate the bronchial artery. Three patients, all males, were treated according to the protocol. A total of 4 BAI therapies were performed with one patient receiving an additional BAI on day 1, cycle 5. Number of treatment cycles before PD was 4, 4, and 6. One patient achieved partial response after cycle 3, and 2 patients obtained stable disease. Toxicities were all grade ≤ 2 including nausea, vomiting, rigor, thrombocytopenia, and anemia. No grade 3 or 4 toxicity reported. Following intravenous administration, mean (±SD) AUCs for gemcitabine, dFdU, and dFdCTP were 19.1 ± 4.76, 1375 ± 722.1, and 591.3 ± 100.2 μM*hr, and following BAI, 9.88 ± 2.67, 889.9 ± 190.3, and 888.3 ± 743.2 μM*hr, respectively. Conclusions: BAI of gemcitabine is feasible and safe at initial dose of 600 mg/m2. A dose-escalating study should be completed to identify maximum tolerated dose and its efficacy. No significant financial relationships to disclose.