OBJECTIVES:

• Determine the objective tumor response rate in chemotherapy-naïve patients with malignant pleural mesothelioma treated with pemetrexed disodium and gemcitabine.
• Determine the median survival of patients with malignant pleural or peritoneal mesothelioma treated with this regimen.
• Determine the time to objective tumor response and duration of response in patients treated with this regimen.
• Determine the time to treatment failure in patients treated with this regimen.
• Determine the time to progressive disease in patients treated with this regimen.
• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the quantitative and qualitative toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and pemetrexed disodium IV over 8-15 minutes on day 8. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 3 months.

PROJECTED ACCRUAL: A total of 18-73 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural or peritoneal mesothelioma of 1 of the following subtypes:

  • Epithelial
  • Sarcomatoid
  • Mixed subtype
• Disease not amenable to curative surgery

• Measurable disease

  • At least 1 measurable lesion at least 20 mm by conventional techniques or at least 10 mm by spiral CT scan
  • At least 1 level on lesion scan must have 1 pleural rind measurement at least 15 mm
  • If there is only 1 measurable lesion, the neoplastic nature must be histologically confirmed
  • Clinically detected lesions are only considered measurable if superficial (e.g., skin nodules and palpable lymph nodes)

  • The following are not considered measurable disease:

    • Pleural effusions
    • Positive bone scans
• No known or suspected brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN*
• ALT and AST no greater than 3 times ULN*
• Albumin at least 2.5 g/dL NOTE: *No greater than 5 times ULN in the case of liver involvement by tumor

Renal

• Creatinine clearance at least 45 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No active infection
• No concurrent serious systemic disorders (including oncologic emergencies) that would preclude study participation
• No other currently active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix (patients with previously treated malignancy are eligible if at less than 30% risk of relapse)
• Able to tolerate folic acid or cyanocobalamin administration

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior intracavitary immunomodulators, unless given for pleurodesis
• No filgrastim (G-CSF) within 24 hours of study chemotherapy administration
• No concurrent immunotherapy
• No concurrent routine colony-stimulating factor therapy
• No concurrent stimulators of thrombopoiesis

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy for cancer

Radiotherapy

• Prior radiotherapy to the target lesion allowed provided the lesion has clearly progressed
• At least 4 weeks since prior radiotherapy
• No concurrent non-palliative radiotherapy

Surgery

• No concurrent surgery for cancer

Other

• At least 2 weeks since prior pleurodesis
• No prior intracavitary cytotoxic drugs, unless given for pleurodesis
• More than 4 weeks since prior investigational agents

• No aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 days of pemetrexed disodium administration

  • No long-acting NSAIDs (e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) within 5 days of pemetrexed disodium administration
• No other concurrent experimental medications (except thymidine)