RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and paclitaxel and giving them in different ways may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal pemetrexed when given together with intraperitoneal cisplatin and paclitaxel in treating patients with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

OBJECTIVES:

Primary

• To determine the maximum-tolerated dose (MTD) of combination therapy comprising intraperitoneal (IP) pemetrexed disodium in combination with IP cisplatin and paclitaxel in patients with optimally debulked stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer in relation to the percentage of patients completing at least 6 courses of treatment.
• To determine the toxicity and the tolerability of this regimen in these patients.

Secondary

• To observe 80% of these patients progression free at 18 months after initiation of chemotherapy.
• To determine, as an exploratory endpoint, the median overall survival of patients treated with this regimen.
• To investigate the pharmacokinetics of this regimen at the determined MTD in these patients.
• To conduct correlative studies on tumor tissue and blood from these patients.

OUTLINE: This is a dose-escalation study of pemetrexed disodium.

Patients receive pemetrexed disodium intraperitoneally (IP) on day 1, cisplatin IP on day 2, and paclitaxel IP on day 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. At least 10 patients are treated at the maximum-tolerated dose (MTD).

Whole blood samples and tumor tissue specimens are obtained from patients at baseline and banked for future DNA, RNA, and protein studies related to prediction of disease progression and treatment resistance. Plasma and intraperitoneal fluid samples may also be collected from patients treated at the MTD for pharmacokinetic analysis of plasma concentrations of pemetrexed disodium by high-performance liquid chromatography (HPLC) or mass spectrometry-HPLC.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically or pathologically confirmed ovarian epithelial carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma

  • Stage III disease

• Meets 1 of the following criteria:

  • No prior treatment and no more than 6 months since primary surgery
  • Platinum-sensitive at second-look surgery with no prior cisplatin therapy

• Must have been optimally debulked to less than 2-cm residual individual tumor plaques or, if suboptimally debulked at first surgery, had chemical debulking

• No mixed Müllerian tumor or borderline ovarian tumor

• No Central nervous system (CNS) or brain metastases

PATIENT CHARACTERISTICS:

• Gynecologic Oncology Group performance status 0-2
• White blood cell count(WBC) ≥ 3,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Serum bilirubin ≤ 2 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST)and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
• Creatinine clearance ≥ 45 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after discontinuation of study drug
• No psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol
• No unstable or preexisting major medical conditions, except cancer-related abnormalities
• No medical life-threatening complications of their malignancies
• No known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV)
• No serious active uncontrolled infections
• No inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg on antihypertensive medications)
• No New York Heart Association grade II-IV congestive heart failure
• No weight loss between 5 to ≤ 10% within the past 14 days that is not related to ascites or paracentesis
• No prior hypertensive crisis or hypertensive encephalopathy
• No myocardial infarction, cerebrovascular accident, transient ischemic attack, or unstable angina within the past 6 months
• No evidence of uncontrollable nausea
• No clinically significant or symptomatic peripheral vascular disease (e.g., aortic aneurysm or aortic dissection)
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
• No pre-existing clinically significant hearing loss
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or adequately treated stage I or II cancer from which the patient is in complete remission
• No known hypersensitivity to any component of pemetrexed disodium
• Able to take folic acid, vitamin B_12, and dexamethasone according to protocol
• No presence of third-space fluid that cannot be controlled by drainage
• No inability to comply with study and/or follow-up procedures

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• May have received up to 4 courses of carboplatin and paclitaxel IV as neoadjuvant chemotherapy for advanced, unresectable disease

• Concurrent low-dose aspirin therapy (i.e., 325 mg/day) allowed

• Concurrent ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) with short elimination half-lives allowed provided ≥ 1 of the following criteria is met:

  • Creatinine clearance (CrCl) > 80 mL/min (i.e., normal renal function)
  • CrCl 45-79 mL/min (i.e., mild to moderate renal insufficiency) AND NSAID dosing interrupted for a period of 2 days before, during, and 2 days after administration of pemetrexed disodium

• Concurrent NSAIDs or salicylates with long half-lives (e.g., naproxen, piroxicam, diflunisal, or nabumetone) allowed provided NSAID dosing is interrupted for at least 5 days before, during, and 2 days after administration of pemetrexed disodium

• No concurrent antineoplastic or antitumor agents not part of the study therapy (i.e., chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy)

• No other concurrent investigational agents