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

Lung Cancer. 2010 May;68(2):240-7. doi: 10.1016/j.lungcan.2009.06.017. Epub 2009 Jul 22.

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 100mg/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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Creatinine / blood
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia / etiology

Substances

  • lipoplatin
  • Deoxycytidine
  • Creatinine
  • gemcitabine
  • Cisplatin