Phase II study of liposomal cisplatin (Lipoplatin™) plus gemcitabine versus cisplatin plus gemcitabine as first line treatment in inoperable (stage IIIB/IV) non-small cell lung cancer

Abstract

Background Lipoplatin is a new liposomal cisplatin designed to reduce cisplatin toxicities without reducing efficacy. In the present randomized phase II study, we examined the efficacy and safety of a Lipoplatin–gemcitabine versus a cisplatin–gemcitabine combination as first line treatment in advanced NSCLC. Patients and methods Patients with advanced (stages IIIB-IV) NSCLC received up to six 21-day cycles of Lipoplatin 120 mg/m 2 (days 1, 8, 15) and gemcitabine 1000 mg/m 2 (days 1 + 8) (arm A; LipoGem) versus cisplatin 100 mg/m 2 (day 1) and gemcitabine 1000 mg/m 2 (days 1 + 8) (arm B; CisGem). The primary objective was objective response rate (ORR). Secondary objectives were disease control rate (DCR), progression-free survival (PFS), duration of response and overall survival (OS). Another secondary objective was safety and tolerability of the LipoGem combination. Results Eighty-eight patients ( n = 88) entered the study; 47 patients were treated with LipoGem versus 41 patients treated with CisGem. Efficacy was assessed in patients who completed at least 1 cycle of treatment; ORR was 31.7% in arm A versus 25.6% in arm B and DCR was 70.7% versus 56.4%, respectively. A preliminary efficacy of LipoGem versus CisGem in the adenocarcinoma histological subtype of NSCLC showed 16.7% versus 45.8% PD. Treatment in arm A was better tolerated with myelotoxicity and a transient mild elevation of serum creatinine as the dominant side effects; the only grade 4 adverse event was neutropenia noted in 2% of the patients. There was a significant reduction in nephrotoxicity in the LipoGem arm (0% versus 5% grade III, p-value < 0.001) as well as in nausea vomiting (2% versus 12% grade III, p-value < 0.001). In addition, less antiemetics and G-CSF were administered in arm A. Conclusion Overall, Lipoplatin appears to have lower toxicity, mainly renal toxicity as well as higher efficacy than cisplatin when combined with gemcitabine in advanced NSCLC.