Pemetrexed and Cisplatin in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

OBJECTIVES:

Primary

• To estimate the antitumor activity of pemetrexed disodium and cisplatin with objective tumor response (partial and complete response) in patients with advanced, persistent, or recurrent carcinoma of the cervix.
• To determine the nature and degree of toxicity of this regimen in these patients.

Secondary

• To determine the effects of this regimen on progression-free survival and overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to prior cisplatin therapy as a radiosensitizer (yes vs no).

Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1-4 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous or nonsquamous cell carcinoma of the cervix

• Advanced, persistent, or recurrent disease
• Disease not amenable to curative therapy
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• Must have ≥ 1 target lesion to be used to assess response

• Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy

PATIENT CHARACTERISTICS:

• GOG performance status 0-2
• Platelet count ≥ 100,000/mm^3
• ANC ≥ 1,500/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Creatinine clearance ≥ 60 mL/min
• SGOT ≤ 2.5 times ULN (≤ 5 times ULN if due to hepatic metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if due to hepatic metastases)
• Negative pregnancy test
• Fertile patients must use effective contraception
• Neuropathy (sensory and motor) ≤ grade 1
• Able to take folic acid, vitamin B12, and dexamethasone according to study protocol
• No history of other invasive malignancies within the past 5 years, except nonmelanoma skin cancer
• No active infection requiring antibiotics with the exception of uncomplicated UTI
• No presence of third space fluid which cannot be controlled by drainage

PRIOR CONCURRENT THERAPY:

• Recovered from effects of recent surgery, radiotherapy, or other therapy
• At least 1 week since prior hormonal therapy directed at the malignant tumor
• At least 4 weeks since prior radiotherapy
• More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and patient remains free of recurrent or metastatic disease
• No prior radiotherapy to any portion of the abdominal cavity or pelvis except for the treatment of cervical cancer
• No prior radiotherapy to more than 25% of marrow-bearing areas
• No prior cancer treatment that contraindicates study treatment
• No prior cytotoxic drugs for advanced or recurrent carcinoma of the cervix

• Prior cisplatin as a radiosensitizer for primary treatment of disease allowed
• No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2-5 days before, during, or for 2 days after receiving pemetrexed disodium

• No NSAIDS with a long half-life (e.g., naproxen, piroxicam, diflunisal, or nabumetone) 5 days before, during, and for 2 days after receiving pemetrexed disodium
• Concurrent hormone replacement therapy is permitted
• Concurrent daily low-dose acetylsalicylic acid therapy (≤ 325 mg/day) allowed
• Concurrent use of acetylsalicylic acid (up to 1.3 g/day) allowed