Randomized phase III trial of Taxol®/Carboplatin versus Taxol®Cisplatin in patients with advanced non-small cell lung cancer

Abstract

platinum or non-platinum chemotherapy von Pawel J1, Manegold C2, Mattson K3, Postmus PE4, Smit EF4, Clarke S5, Saarinen A.1 Asklepios FachkIinik MŸnchen-Gauting, Germany; 2Thoraxklinik, Heidelberg, Germany; 3Division of Pulmonary Medicine, Helsinki University Central Hospital, Finland; 4Department of Pulmonary Diseases, Vrije Universiteit Amsterdam, 5Sydney Cancer Center, Sydney, Australia Purpose: Although new chemotherapeutic agents for NSCLC have been introduced, a critical need for active second-line agents still exists. This study evaluates the activity of MTA (multitargeted antifolate), in the treatment of NSCLC pts who relapsed following front-line therapy. MTA inhibits multiple folate-dependent enzymes and has activity in multiple tumors, i.e. NSCLC, breast, mesothelioma, head and neck, pancreas, and colon cancers. Methods: Pts with Stage IIIb or IV NSCLC who had relapsed during or within 3 months of prior therapy entered into 2 cohorts, depending on whether their prior therapy did (PT) or did not contain platinum (NP) (i.e. mitomycin, docetaxel, paclitaxel, vinorelbine, and/or gemcitabine). All pts received MTA 500 mg/m2 every 21 days with prophylactic dexamethasone. Results: 43 of 67 pts enrolled are evaluable for response. In the PT arm, 3 partial responses (PRs) were reported, for an overall response rate (RR) of 13%. In the NP arm, 1 complete and 5 PRs in 20 evaluable pts was reported, for a RR of 30%. Grade 3/4 toxicity (as % of cycles) includes Hgb: 6/1, WBC: 19/3, ANC: 14/9, platelets: 3/4, bilirubin: 2/0, elevated transaminases: 3/0, and infection: 1/2, respectively. One pt discontinued due to drug-related pneumonia. Four on-study deaths are not thought to be drug-related. Conclusion: MTA is active in the second-line treatment of NSCLC and appears noncross resistant with a variety of front-line agents.