Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2009 Oct 1;27(28):4649-55.
doi: 10.1200/JCO.2009.21.8909. Epub 2009 Aug 31.

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

Bradley J Monk  1 , Michael W Sill, D Scott McMeekin, David E Cohn, Lois M Ramondetta, Cecelia H Boardman, Jo Benda, David Cella
Affiliations
Clinical Trial

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

Bradley J Monk et al. J Clin Oncol. .

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.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
CONSORT flow diagram. Initially, 41 patients were registered onto a randomized phase III trial comparing two arms, paclitaxel + cisplatin (PC) versus vinorelbine + cisplatin (VC). On January 26, 2004, the trial was amended to include two additional arms: gemcitabine + cisplatin (GC) and topotecan + cisplatin (TC). The initial 41 patients were excluded from the primary analysis. Additional analyses with these patients and with all of the ineligible patients yielded the same qualitative conclusions with regard to treatment efficacy. prog, progression.
Fig 2.
Fig 2.
(A) Overall survival Kaplan-Meier plots for the 434 patients in the study sample and (B) hazard ratios with 95% CIs adjusted for multiplicity, using Dunnett's procedure. (C) Progression-free survival Kaplan-Meier plots for the 434 patients in the study sample and (D) hazard ratios with 95% CIs adjusted for multiplicity, using Dunnett's procedure. Cis + Pac, cisplatin + paclitaxel; Cis + Vin, cisplatin + vinorelbine; Cis + Gem, cisplatin + gemcitabine; Cis + Top, cisplatin + topotecan; Rel Haz, relative hazard; Var, Variance; ln, natural logarithm; HR, hazard ratio.
Fig 3.
Fig 3.
(A) Hazard ratios for overall survival with 95% CIs adjusted for treatment regimen and disease status, investigating the potential prognostic impact of race (black not statistically significant), performance status (patients with performance status = 1 indicate worse prognosis), disease site (patients with target lesion in a previously irradiated zone indicate worse prognosis), and ethnicity (patients of Hispanic origin indicate improved prognosis). (B) Hazard ratios of overall survival for disease status with 95% CIs, adjusted for treatment, race, ethnicity, performance status, and disease site. The status of disease was classified into three categories: advanced disease, recurrent disease, and persistent disease. Persistent disease was classified as evidence of disease following initial therapy. Recurrent disease was further broken down by the progression-free interval since the date of diagnosis. All hazard ratios are relative to patients with advanced disease. Rel Haz, relative hazard; Var, Variance; ln, natural logarithm; HR, hazard ratio; PFI, progression-free interval.
See this image and copyright information in PMC

References

    1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. - PubMed
    1. American Cancer Society. Cancer Facts and Figures 2008. http://www.cancer.org/docroot/STT/stt_0_2008.asp?sitearea=STT&level=1.
    1. Monk BJ, Herzog TJ. The evolution of cost-effective screening and prevention of cervical carcinoma: Implications of the 2006 consensus guidelines and human papillomavirus vaccination. Am J Obstet Gynecol. 2007;197:337–339. - PubMed
    1. Monk BJ, Tewari KS. Invasive cervical cancer. In: DiSaia PJ, Creasman WT, editors. Clinical Gynecologic Oncology. ed 7. Philadelphia, PA: Mosby; 2007. pp. 55–124.
    1. Monk BJ, Tewari KS, Koh WJ. Multimodality therapy for locally advanced cervical carcinoma: State of the art and future directions. J Clin Oncol. 2007;25:2952–2965. - PubMed

Publication types

MeSH terms