RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes
necessary for tumor cell growth. Drugs used in chemotherapy such as gemcitabine use
different ways to stop tumor cells from dividing so they stop growing or die. Combining
pemetrexed disodium with gemcitabine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving pemetrexed disodium together with
gemcitabine works in treating patients with pleural or peritoneal malignant mesothelioma.
- 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
- Determine the quantitative and qualitative toxic effects of this regimen in these
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.
- Histologically confirmed malignant pleural or peritoneal mesothelioma of 1 of the
- 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
- If there is only 1 measurable lesion, the neoplastic nature must be
- 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
- 18 and over
- ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9 g/dL
- 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
- Creatinine clearance at least 45 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
- 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:
- 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
- No prior systemic chemotherapy
- No other concurrent chemotherapy
- No concurrent hormonal therapy for cancer
- Prior radiotherapy to the target lesion allowed provided the lesion has clearly
- At least 4 weeks since prior radiotherapy
- No concurrent non-palliative radiotherapy
- No concurrent surgery for cancer
- 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)