Oxaliplatin and fixed-rate infusional gemcitabine in the second-line treatment of patients with metastatic colon cancer: final results of a Phase II trial prematurely closed as a result of poor accrual.

Background: Second-line therapy of advanced colorectal cancer (CRC) after failure of a combination of irinotecan, a fluoropyrimidine, and bevacizumab includes the use of oxaliplatin and a fluoropyrimidine. In animal models, synergistic effects of gemcitabine and platinum agents have been established. Additionally, superior antitumor activity of prolonged administration of gemcitabine compared with bolus administration has been demonstrated in vivo against murine colon tumors.

Patients And Methods: A 2-stage phase II trial was developed to assess the efficacy (primary endpoint: response rate) and safety of gemcitabine 1000 mg/m(2) over 100 minutes on days 1 and 15 in combination with oxaliplatin 100 mg/m(2) over 2 hours on days 2 and 16, every 4 weeks. Patients with metastatic CRC in whom irinotecan and a fluoropyrimidine treatment had failed were enrolled. Calcium and magnesium infusion was routinely given before and after oxaliplatin administration.

Results: Because of slow accrual as a result of oxaliplatin becoming more commonly used in first-line treatment, the trial was stopped with only 10 patients enrolled. Eight were men and 2 were women. Median age was 58.5 years (range, 47-72 years). Nine patients had an Eastern Cooperative Oncology Group performance status of 0/1. A median of 3.5 cycles was administered (range, 1-9; total, 42). Six patients had stable disease and 1 had progressive disease. Two patients had confirmed partial responses, and 1 patient had a partial response but developed necrotizing fasciitis, declined surgical treatment, and died before a confirmatory scan could be performed. The regimen was otherwise well tolerated: 1 patient developed grade 3 neutropenia. With a median follow-up of 5.5 months, 4 patients have died. The time to treatment failure was 3.7 months.

Conclusion: Despite premature study closure because of poor accrual, oxaliplatin in combination with fixed-rate infusional gemcitabine seems to be a safe and potentially effective regimen in the treatment of CRC. Further studies should be considered with the addition of targeted therapy.