Phase II Study of Pemetrexed as Second or Third LineCombined Chemotherapy in Patients with Colorectal Cancer

Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second orthird line in patients with stage IV colorectal cancer (CRC). Patients and
Methods: This trial was conductedto evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectalcarcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histologicaldiagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patientsreceived pemetrexed at a dose of 500 mg/m2 by 10 minute infusion on day 1, repeated every 21 days. Doses weremodified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum.
Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not haverepeat radiological testing to determine response because he went off study after only one cycle of treatmentfor economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive diseasewere recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose ofpemetrexed 500 mg/m2. Median time to progression for all eligible patients was 2.5 months. The most commontoxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting,constipation, abdominal pain, diarrhea, and skin rash.
Conclusion: Pemetrexed at 500 mg/m2 given every threeweeks combined with chemotherapy is associated with moderate response and good tolerability in patients withstage IV CRC