Pemetrexed Plus Cisplatin as First-Line Treatment in Stage IV or Recurrence of Gastric Cancer

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the gastric. Stage IV disease, not amenable to curative surgery, or disease recurrence after prior surgery.
• Disease status must be that of measurable disease with presence of at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• In bidimensionally measurable lesions the longest diameter should be selected for measurement.
• Tumor lesions in areas of prior radiation therapy may be included only if they were clearly progressing.
• If only a single lesion is present in a patient who had prior therapy for gastric adenocarcinoma, the neoplastic nature of the lesion should be confirmed by cytology and/or histology.
• Ultrasound and clinical examination are not allowed for assessment of measurable disease.
• Elevation of tumor markers, pleural or pericardial effusion, ascites, bone lesions, cystic lesions, or carcinomatous lymphangitis pulmonis/cutis is defined as not being measurable.
• Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Scale.
• Estimated life expectancy of at least 12 weeks.
• No prior chemotherapy or radiotherapy.
• Patient compliance and geographic proximity that allow adequate follow-up.

Adequate organ function including the following:

• Bone marrow: absolute neutrophil count 1.5 x 10 to the ninth power/liter (L), platelets 100 x 10 to the ninth power/L, hemoglobin >=9 grams per deciliter (g/dL).
• Hepatic: bilirubin <=1.5 x upper limit of normal (ULN); alkaline phosphatase, aspartate transaminase and alanine transaminase <=3.0 x ULN.
• Renal: Calculated creatinine clearance >=45 milliliters (ml)/minute.
• Men or women, age 18 to 70 years.
• For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding.
• For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period.
• Signed informed consent from patient.

Exclusion Criteria:

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Concurrent administration of any other tumor therapy.
• Active infection.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Pregnancy.
• Breast-feeding.
• History of significant neurological or mental disorder, including seizures or dementia.
• Have had a prior malignancy other than gastric cancer, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence.
• Patients with a history of low grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs 2 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin.
• If a patient is taking a nonsteroidal anti-inflammatory drug (NSAID) or salicylate with a long half-life it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin.
• Clinically significant ascites or pleural effusion that is apparent at clinical examination and cannot be controlled by drainage or other procedures prior to study enrollment. NOTE: Small effusions noted on computed tomography (CT) scan do not exclude the patient from study enrollment.
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.
• Known or suspected brain metastasis. Patients who have clinical signs or symptoms that are suspicious of brain metastasis must have a pretreatment CT or magnetic resonance imaging (MRI) of the brain. A patient with documented brain metastasis, at the time of consideration for study entry or in the past, will be excluded from entering in the study.