Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non-small-cell lung cancer: A phase II study

Purpose: To evaluate the efficacy and safety of the multitargeted antifolat e LY231514 (MTA) in patients receiving initial chemotherapy for unresectabl e, advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with measurable,advanced NSCLC who had not r eceived previous chemotherapy for advanced disease were considered for this study Eligible patients who gave written informed consent initially receiv ed MTA 600 mg/m(2) intravenously (IV) for 10 minutes every 3 weeks. After t hree patients received treatment at this dose, the dose was reduced to 500 mg/m2 IV at the same infusion time and frequency because of toxicity seen i n this study and another Canadian MTA trial in colorectal cancer. Patients received vp to four cycles after complete or partial remission or six cycle s after stable disease was documented. Results: Thirty-three patients were accrued onto the study. All were assess able for toxicity, and 30 patients were assessable for response, All but on e patient had an Eastern Cooperative Oncology Group performance status scor e of 0 or 1, 18 patients (55%) had adenocarcinoma, and nine patients (27%) had squamous cell carcinoma. Twenty-five patients (76%) had stage IV diseas e, and the remainder had stage IIIB disease at trial entry, Seven patients experienced a confirmed partial response and no complete responses were see n; thus, the overall response rate was 23.3% (95% confidence interval, 9.9% to 42.3%), The median duration of response was 3.1 months (range, 2.3 to 1 3.5 months) alter a median follow-vp period of 7.9 months. Four (67%) of si x patients with stage IIIB disease and three (12.5%) of 24 with stage IV di sease responded to treatment. Four patients (13.3%) experienced febrile neu tropenia and 13 (39%) experienced grade 3 or 4 neutropenia, whereas only on e patient (3%) developed grade 4 thrombocytopenia. Nonhematologic toxicity was generally mild or moderate, but 39% of patients developed a grade 3 ski n rash. Most other toxicities comprised grade 1 or 2 stomatitis, diarrhea, lethargy, and anorexia. Ten patients stopped protocol therapy because of to xicity. Conclusion: MTA seems to have clinically meaningful activity as a single ag ent against advanced NSCLC. Toxicity is generally mild and tolerable. Furth er study of this agent in combination with cisplatin and other active drugs is warranted in this disease. (C) 1999 by American Society of Clinical Onc ology.