Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial

Inclusion Criteria:

- Histologically or cytologically confirmed advanced mesothelioma of the pleura

- Measurable disease, as defined by RECIST criteria, within 4 weeks of randomization.
Patients with pleural rinds not measurable by RECIST were eligible if disease was
evaluable within 4 weeks of randomization using mesothelioma response criteria

- May have undergone pleurodesis. If pleurodesis was performed, there must have been
at least a 2-week delay before Pemetrexed administration. A CT must have been
performed after 2 weeks after pleurodesis to serve as the baseline scan.

- ECOG Performance Status of 0 or 1

- Normal organ and marrow function, as defined by:

- Absolute neutrophil count ≥ 1,500/ul

- Platelet count ≥ 100,000/ul

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)

- Albumin ≥ 2.5 g/dL

- Creatinine clearance ≥ 45 mL/min or Creatinine ≤ 2.0 g/dL

- Age 18 years and over

- Able to take folic acid and cyanocobalamin (vitamin B12)

- Willing and able to take dexamethasone

- Women of childbearing potential and sexually active men were required to use
contraception during and for the first 3 months after the study

Exclusion Criteria

- A candidate for curative surgery

- Prior radiation therapy to the target lesion, unless the lesion was clearly
progressing per RECIST criteria after prior radiation and the interval between the
most recent radiation therapy and enrollment was at least 4 weeks

- Prior systemic chemotherapy for mesothelioma. Prior intracavitary cytotoxic drugs or
immunomodulators were not permitted, unless given for the purpose of pleurodesis.

- Active infection or serious concomitant systemic disorder

- Second primary malignancy, other than in situ malignancies or adequately treated
basal cell carcinoma of the skin or other malignancy treated at least 3 years
previously with no evidence of recurrence.

- Treatment with an investigational agent within 4 weeks before enrollment

- Known or suspected brain metastases

- Women must not be pregnant or breastfeeding

- Obviously malnourished or with a weight loss of greater than 10% in the preceding 6
weeks

- Aspirin or other nonsteroidal anti-inflammatory drugs for 2 days before, during, and
for 2 days after each administration of pemetrexed disodium (5 days before, during,
and 2 days after each administration of pemetrexed disodium for piroxicam, naproxen,
diflunisal, or nabumetone)