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