Inclusion Criteria:

• Patients must have histologically confirmed malignant pleural or peritoneal mesothelioma epithelial, sarcomatoid, or mixed subtype, not amenable to curative treatment with surgery. Patients with pleural mesothelioma will be clinically staged using the IMTG TNM staging criteria (see Protocol Attachment 1). Note that there is no staging system for peritoneal mesothelioma and those patients will only be followed for survival. Patients may be entered based on local pathology.

• Disease status must be that of measurable disease as defined by modified SWOG criteria.

  • Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology (see Section 3.8.1.2).
  • Measurable lesions: Lesions that can be accurately measured in at least one dimension with the longest diameter ≥20 mm using conventional techniques or ≥10 mm using spiral CT scans. At least one level must have one rind measurement ≥15 mm.
• CT (specifically spiral CT) scans and MRT are the preferred methods of measurement.
• Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes).
• For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required.

NOTE: Neither pleural effusions nor positive bone scans are considered measurable.

• Patients may have undergone pleurodesis. If pleurodesis was performed, there must be at least a 2-week delay before Oxaliplatin or gemcitabine is administered. If the original CT scan occurred prior to the pleurodesis, an additional CT scan is required 2 weeks or longer after the pleurodesis, which will then be considered the baseline scan.

NOTE: For patients with clinically significant pleural effusions or ascites, consideration should be given to draining the fluid.

• Performance status of 0, 1 or 2 on ECOG Performance Status Scale (after any palliative measures including pleural drainage have occurred). See Protocol Attachment 2.
• Estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

• More than one previous regimen of systemic chemotherapy. Prior intracavitary cytotoxic drugs will count as a prior regimen, unless given for the purpose of pleurodesis. Immunomodulators will not be regarded as chemotherapy. Prior systemic treatment with pemetrexed plus a platinum compound will not be a contraindication for gemcitabine-oxaliplatin.
• Prior radiation therapy to the target lesion, unless the lesion is clearly progressing and the interval between the most recent radiation therapy and enrollment is at least 4 weeks.
• Active infection (at the discretion of the investigator).
• Pregnancy or breast feeding.
• Serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator).
• Patients with a "currently active" second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix are not to be registered. Patients who are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
• Use of any investigational agent within 4 weeks before enrollment into the study.
• Disease which cannot be radiologically imaged.