There is no standard treatment for the patient population being asked to participate in this study. Although one current regimen, used by some investigators, has a high rate of response compared to other therapies, it is associated with moderate to severe toxicity. As gemcitabine and pemetrexed have a broad range of activity against cancer it is reasonable to determine how active and safe they are against patients with this type of cancer.The objective of this study is to determine the anti-tumor activity of pemetrexed and gemcitabine in patients with this condition.

Inclusion Criteria:

• Histologically proven adenocarcinoma
• No obvious primary on routine history, physical examination, and investigations
• Patients greater than or equal to 18 years of age
• ECOG Performance Status 0-1
• Patients requiring opioids for pain control must be on a fixed analgesic regimen aimed to provide adequate pain control with no more than 3 breakthrough (supplemental) doses of analgesics per day to control pain; Additional inclusion criteria due apply, but not are not listed here.

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
• Unable to stabilize pain and analgesics for a period of 7 days prior to starting study treatment
• Prior treatment with chemotherapy
• Bilirubin greater than or equal to 40 mol/L
• AST or ALT greater than or equal to 5 times the upper limit of normal (ULN); Additional exclusion criteria due apply, but not are not listed here.