Comparison of Four Combination Chemotherapy Regimens Using Cisplatin in Treating Patients With Stage IVB, Recurrent, or Persistent Cancer of the Cervix

RATIONALE: Drugs used in chemotherapy such as cisplatin, paclitaxel, vinorelbine, gemcitabine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen containing cisplatin is most effective in treating cervical cancer.

PURPOSE: This randomized phase III trial is studying four combination chemotherapy regimens using cisplatin to compare how well they work in treating women with stage IVB, recurrent, or persistent cancer of the cervix.

OBJECTIVES:

• Compare the survival and response of patients with stage IVB, recurrent, or persistent carcinoma of the cervix when treated with paclitaxel and cisplatin vs vinorelbine and cisplatin vs gemcitabine and cisplatin vs topotecan and cisplatin.
• Compare the toxic effects of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 1-4 hours on day 2.
• Arm II: Patients receive vinorelbine IV over 6-10 minutes on days 1 and 8 and cisplatin IV over 1-4 hours on day 1.
• Arm III: Patients receive gemcitabine IV over 30-60 minutes on days 1 and 8 and cisplatin as in arm II.
• Arm IV: Patients receive topotecan IV over 30 minutes on days 1-3 and cisplatin as in arm II.

In all arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before courses 2 and 5, and at 9 months after study entry.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients (150 per treatment arm) will be accrued for this study within 4 years.

• Drug: cisplatin
• Drug: gemcitabine hydrochloride
• Drug: paclitaxel
• Drug: topotecan hydrochloride
• Drug: vinorelbine tartrate

• Cella D, Huang HQ, Monk BJ, Wenzel L, Benda J, McMeekin DS, Cohn D, Ramondetta L, Boardman CH. Health-related quality of life outcomes associated with four cisplatin-based doublet chemotherapy regimens for stage IVB recurrent or persistent cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 Dec;119(3):531-7. Epub 2010 Sep 15.
• Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, Benda J, Cella D. 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. Epub 2009 Aug 31.
• Monk BJ, Sill M, McMeekin DS, et al.: A randomized phase III trial of four cisplatin (CIS) containing doublet combinations in stage IVB, recurrent or persistent cervical carcinoma: a Gynecologic Oncology Group (GOG) study. [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA5504, 2008.
• Wenzel LB, Huang H, Cella D, et al.: Quality-of-life results of a randomized phase III trial of four cisplatin (Cis) containing doublet combinations in stage IVB cervical carcinoma: A gynecologic oncology group (GOG) study. [Abstract] J Clin Oncol 26 (Suppl 15): A-5529, 2008.
• Chase DM, Huang HQ, Wenzel L, Cella D, McQuellon R, Long HJ, Moore DH, Monk BJ. Quality of life and survival in advanced cervical cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 2012 Feb 1. [Epub ahead of print]
• Paton F, Paulden M, Saramago P, Manca A, Misso K, Palmer S, Eastwood A. Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix. Health Technol Assess. 2010 May;14 Suppl 1:55-62.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix

  • Stage IVB, recurrent, or persistent disease
• Not amenable to curative surgery and/or radiotherapy

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by spiral CT scan
  • Biopsy confirmation required if lesion is less than 30 mm
  • Target lesion must be outside of a previously irradiated field
• No craniospinal metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• GOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times normal
• Alkaline phosphatase no greater than 3 times normal
• AST no greater than 3 times normal

Renal

• Creatinine ≤ 1.2 mg/dL OR
• Creatinine > 1.2 mg/dL but < 1.5 mg/dL AND creatinine clearance ≥ 50 mL/min
• No bilateral hydronephrosis not alleviated by ureteral stents or percutaneous drainage

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No prior or concurrent malignancy within the past 5 years except nonmelanoma skin cancer
• No prior malignancy whose treatment contraindicates the current study therapy
• No concurrent clinically significant infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent cytokines

Chemotherapy

• At least 6 weeks since prior chemoradiotherapy and recovered
• No prior chemotherapy (except when concurrently administered with radiotherapy)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• See Chemotherapy
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• Recovered from prior surgery