Raltitrexed + Oxaliplatin for Advanced Colorectal Cancer

SAN FRANCISCO—Raltitrexed (Tomudex) in combination with oxaliplatin may be used as a replacement for the de Gramont regimen in advanced colorectal cancer, said Vincenzo Catalano, MD, Medical Oncology, Pesaro, Italy.

The combination offers equivalent efficacy with more convenient dosing, he said. (Both agents are investigational in the United States.)

Oxaliplatin, Dr. Catalano noted, has shown activity in the treatment of advanced colorectal cancer, mainly in combination with fluorouracil (5-FU) and folinic acid administered in the de Gramont schedule (5-FU bolus plus 22-hr infusion) repeated every 2 weeks.

Raltitrexed, a potent, specific thymidylate synthase inhibitor, has the advantage of allowing every-3-week administration of a 15-minute infusion, Dr. Catalano said in an interview at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 576).

Dr. Catalano’s phase II multicenter trial enrolled 60 patients (median age, 61 years) who were chemonaïve or who had completed prior adjuvant chemotherapy at least 6 months before the current study. All patients had confirmed, relapsed, or metastatic colorectal cancer. Prevalent metastatic sites were the liver in 45 patients, lungs in 16 patients, and lymph nodes in 6 patients.

Treatment Regimen

Treatment consisted of raltitrexed 3 mg/m² (15-minute intravenous infusion) followed by oxaliplatin 100 mg/m² (2-hour intravenous infusion), repeated every 3 weeks. At the time of the presentation, 41 patients had received three or more cycles of chemotherapy and 19 were ongoing.

Among 39 patients evaluable for response, partial responses were reported in 17 patients for an overall response rate of 41.5%. Fourteen patients (34.1%) had stable disease, and 8 (19.5%) had disease progression.

Toxicity evaluation for 58 evaluable patients (receiving 236 cycles of chemotherapy) showed neutropenia to be the most common hematologic toxicity (seen in 15% of chemotherapy cycles). Only three patients, however, experienced grade 3 neutropenia.

Dr. Catalano said that the most common nonhematologic adverse events (grades 1-3) were nausea/vomiting (30 cycles), asthenia (37 cycles), and transient elevations of hepatic transaminase (46 cycles).

The one case of grade 4 toxicity reported (asthenia) resulted in the sole toxicity withdrawal from the study. There were no drug-related deaths.

‘An Effective First-Line Treatment’

Dr. Catalano concluded that the combination of raltitrexed and oxaliplatin is "an effective first-line regimen for the treatment of advanced colorectal cancer" that is convenient and well tolerated by patients.

Pointing to the greater convenience of the 3-week schedule of outpatient therapy with 3 weeks of rest, Dr. Catalano commented that "raltitrexed could replace the infusional 5-FU regimen." Relative to 5-FU, activity and tolerability are equivalent, he said.

Dr. Catalano noted also that with a median follow-up of 8 months, median time to survival had not been reached. During that period, 26 patients have received second-line chemotherapy—24 received irinotecan (Camptosar) and 2,5-FU infusion—and 10 have died.