Carboplatin and Topotecan in Treating Patients With Relapsed or Metastatic Cervical Cancer

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of topotecan hydrochloride when administered with carboplatin in patients with relapsed or metastatic cervical cancer. (Phase I)
• To determine the objective response rate in patients treated with this regimen. (Phase II)

Secondary

• To determine the dose-limiting toxicities of this regimen in these patients. (Phase I)
• To assess the progression-free survival of patients treated with this regimen. (Phase II)
• To assess the overall survival of patients treated with this regimen. (Phase II)
• To assess the tolerability of this regimen in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of topotecan hydrochloride followed by a phase II study.

Patients receive oral topotecan hydrochloride on days 1, 8, and 15 and carboplatin IV on day 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete a quality-of-life questionnaire at baseline and then every 3 months thereafter.

After completion of study therapy, patients are followed every 3 months for 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed cervical cancer, including the following cell types:

• Squamous cell carcinoma
• Adenocarcinoma
• Adenosquamous cell carcinoma
• Metastatic disease or in first relapse

• Not curable by surgery and/or radiotherapy with or without chemotherapy
• At least 1 non-irradiated measurable lesion
• No CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Transaminases ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN in the presence of liver metastases)
• Total bilirubin ≤ 1.5 times ULN
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other cancer within the past 5 years except for adequately treated basal cell or squamous cell carcinoma of the skin
• No swallowing disorders or gastrointestinal disease resulting in an inability to take oral medication or a requirement for IV alimentation
• No altered intestinal absorption
• No peptic ulcers
• No nephrostomy

• Double-J catheter allowed
• None of the following cardiovascular conditions within the past 6 months:

• Uncontrolled hypertension
• Coronary artery disease
• NYHA class III or IV congestive heart failure
• Ventricular arrhythmia
• Unstable angina
• Myocardial infarction
• No infection or serious illness that would preclude study treatment
• No contraindications to study treatment
• No psychological, familial, sociological, or geographical condition that would preclude follow-up

PRIOR CONCURRENT THERAPY:

• No prior cytotoxic therapy except for chemoradiotherapy or pelvic radiotherapy
• At least 6 months since prior platinum-based chemoradiotherapy
• No concurrent participation in another clinical trial that could interfere with the objectives of this study