ASCO: Cetuximab (Erbitux) with Oral Chemo Works in Metastatic Colorectal CA

CHICAGO, June 7 -- A new regimen that includes both a targeted agent and cytotoxic drugs appears to be at least as effective as standard regimens for the treatment of unresectable metastatic colorectal cancer.

So said researchers at the American Society of Clinical Oncology meeting here. They reported results of a phase II trial of cetuximab (Erbitux) added to the tegafur-uracil plus leucovorin and irinotecan regimen known as TEGAFIRI - creating a new acronym: CETUFTIRI

The international team said 47% of 53 study patients achieved either a complete or partial response based on the Response Evaluation Criteria in Solid tumors (RECIST). Eight other patients were not included in the results because of early discontinuation, the researchers reported.

"The CETUFTIRI study has shown that the combination of tegafur-uracil and irinotecan-based chemotherapy with cetuximab has comparable efficacy with FOLFIRI (5-fluorouracil, leucovorin and irinotecan) plus cetuximab," said Jaafar Bennouna, MD, a medical oncologist at Centre Rene Gauducheau, Nantes, France.

"CETUFTIRI has the added advantage of the convenience of an oral regimen," Dr. Bennouna said. "CETUFTIRI is generally well tolerated with no hand-foot syndrome of any grade reported."

Although the combination of 5-fluorouracil and leucovorin is widely used, the researchers noted that "intravenous administration of 5-fluorouracil results in a rapid decline in plasma concentrations following bolus administration and poor tolerability, while continuous infusion is associated with the inconvenience of portable pumps and the risk of thrombosis or infection."

"The tegafur-uracil combination belongs to a class of orally active fluoropyrimidine drugs developed to overcome these difficulties," Dr. Bennouna said. "Clinical studies have shown that tegafur-uracil is as effective as intravenous bolus 5-fluorouracil and significantly better tolerated."

In the CETUFTIRI regimen, patients received an initial dose of cetuximab, 400 mg/m² in a two-hour intravenous infusion at the start of therapy followed by 250 mg/m² on day 8 and day 15 in a 21-day cycle. Tegafur-uracil 250 mg/m2 and leucovorin 90 mg are taken orally every three hours on days 1 through 14.

In the phase II trial, Dr. Bennouna observed two complete responses and 23 partial responses. In addition, the disease stabilized in 17 patients, providing a total disease control rate of 79%.

Dr. Bennouna said the new regimen was superior to TEGAFIRI, which had shown a 34% objective response rate, and equivalent to FOLFIRI, which has demonstrated a 45% objective response rate.