Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study

J Clin Oncol. 2009 Oct 1;27(28):4649-55. doi: 10.1200/JCO.2009.21.8909. Epub 2009 Aug 31.

Abstract

Purpose: Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma.

Patients and methods: Patients were randomly assigned to paclitaxel 135 mg/m(2) over 24 hours plus Cis 50 mg/m(2) day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m(2) days 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m(2) day 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (GC); or topotecan 0.75 mg/m(2) days 1, 2, and 3 plus Cis 50 mg/m(2) day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected.

Results: A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia.

Conclusion: VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Fatigue / chemically induced
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leukopenia / chemically induced
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Prognosis
  • Quality of Life
  • Topotecan / administration & dosage
  • Topotecan / adverse effects
  • Treatment Outcome
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives
  • Vinorelbine
  • Young Adult

Substances

  • Deoxycytidine
  • Vinblastine
  • Topotecan
  • gemcitabine
  • Paclitaxel
  • Cisplatin
  • Vinorelbine