Topotecan, Cisplatin, and Radiation Therapy in Treating Patients With Advanced Cervical Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of topotecan when administered with cisplatin in patients with advanced cervical cancer.
• Identify any unique toxicities associated with administering radiotherapy along with adjuvant cisplatin and topotecan in patients with cervical cancer.
• Determine the feasibility of administering continuous infusion topotecan chemotherapy together with radiation therapy.
• Assess the quality of life of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of topotecan.

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Some patients may also undergo brachytherapy. Patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36 and topotecan IV continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline and at 4 and 14 weeks after completion of study treatment.

After completion of study treatment, patients are followed periodically.

Inclusion criteria

• Histologically confirmed cervical carcinoma

• Deemed not curable by surgery or radiotherapy alone
• The following stages are eligible:

• Stage IIB
• Stage IIIA or IIIB
• Stage IVA
• Stage IB or IIA with ≥ 1 of the following risk factors:

• Primary tumor ≥ 6 cm
• Positive pelvic and/or para-aortic lymph nodes (resected or unresected)
• Positive surgical margins
• Depth of invasion > 50% and positive capillary-lymphatic space involvement
• The following histologic subtypes are eligible:

• Squamous
• Adenosquamous
• Adenocarcinoma
• No recurrent cervical cancer
• Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
• White blood cells (WBC) ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Granulocyte count ≥ 1,500/mm^3
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 1.5 times institutional normal
• Serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase ≤ 3 times institutional normal
• No other prior or concurrent malignancies other than skin (excluding melanoma)
• No septicemia, severe infection, gastrointestinal bleeding, or intestinal obstruction
• No anatomic abnormalities (e.g., pelvic kidney or renal transplant) requiring modification of radiation fields
• Fertile patients must use effective contraception
• Negative pregnancy test
• Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) are eligible if disease is stable for the past 6 months
• Recovered from recent surgery

Exclusion criteria

• Prior pelvic radiation
• Pregnant or nursing
• History of thrombus
• History of unstable angina or myocardial infarction within the past 6 months