Originally published as JCO Early Release 10.1200/JCO.2009.23.1548 on August 31 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Socinski, M. A. Articles by Thatcher, N. PubMed PubMed Citation Articles by Socinski, M. A. Articles by Thatcher, N. Social Bookmarking                            What's this?

Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer

From the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; Vrije University Medical Center, Amsterdam; Eli Lilly Netherlands, Utrecht, the Netherlands; Christie Hospital, Manchester, United Kingdom; US Oncology, Houston, TX; Hospital Grosshansdorf, Grosshansdorf; Department of Medicine and Medical Oncology, St Georg Hospital, Hamburg, Germany; Mazovian Center of Lung Diseases and Tuberculosis, Otwock; Sokolowski Specialist Hospital in Szczecin-Zdunowo; Medical University of Gdask, Gdask, Poland; The West Clinic, Memphis, TN; St Petersburg Oncology Center, St Petersburg, Russian Federation; Cancer Institute "Ion Chiricuta," Cluj-Napoca; "A. Trestioreanu" Oncology Institute, Bucharest University, Bucharest, Romania; Eli Lilly and Company, Indianapolis, IN.

Corresponding author: Mark A. Socinski, Lineberger Comprehensive Cancer Center, Physician's Office Bldg, 3rd Floor, 170 Manning Dr, CB# 7305, University of North Carolina, Chapel Hill, NC 27599; e-mail: socinski{at}med.unc.edu.

Purpose Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC).

Patients and Methods Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m² on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m² on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin.

Results Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm.

Conclusion Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.

Supported by Eli Lilly, Indianapolis, IN.

Presented in part as an oral presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and the 8th Annual Targeted Therapies for the Treatment of Lung Cancer Meeting, February 20-23, 2008, Santa Monica, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00363415 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?