ROCKVILLE, Maryland-The FDA has approved a new indication for Eloxatin (oxaliplatin for injection, Sanofi-Synthelabo)-as a treatment combined with conventional chemotherapy for the postsurgical treatment of patients with stage III colon cancer after complete tumor resection. The drug, as with its previous two US approvals, is to be used in combination with infusional fluorouracil/leucovorin (5-FU/LV). The company noted that the supplemental approval provides the first new adjuvant treatment for colon cancer in more than a decade.
ROCKVILLE, MarylandThe FDA has approved a new indication for Eloxatin (oxaliplatin for injection, Sanofi-Synthelabo)as a treatment combined with conventional chemotherapy for the postsurgical treatment of patients with stage III colon cancer after complete tumor resection. The drug, as with its previous two US approvals, is to be used in combination with infusional fluorouracil/leucovorin (5-FU/LV). The company noted that the supplemental approval provides the first new adjuvant treatment for colon cancer in more than a decade.
"Early postsurgical treatment with this Eloxatin-based regime offers patients the greatest opportunity of living longer without recurrence of their disease," said John L. Marshall, MD, of Georgetown University. "The approval marks the beginning of a promising new era of benefit for patients with colon cancer."
The FDA initially approved Eloxatin in August 2002 for the second-line treatment of advanced colorectal cancer, and granted it first-line approval in January 2004. The new approval was based on the MOSAIC study, an international phase III trial that involved 2,246 patients treated at 146 medical facilities. Participants were randomized to receive either Eloxatin plus infusional 5-FU/LV or infusional 5-FU/LV alone.
At a median follow-up of 4 years, patients receiving Eloxatin showed a significant improvement in disease-free survival, the study’s primary endpoint, compared with placebo. Overall, the treatment arm had a 4-year disease-free survival rate of 75.9%, compared with 69.1% for the control group (P = .0008). Among patients with stage III disease, those receiving Eloxatin had a 69.7% disease-free survival rate vs 61.0% for the control arm (P = .002). Moreover, the Eloxatin/5-FU/LV group had a 24% lower risk of cancer recurrence than the overall patient population that had undergone surgery to remove their primary tumor.
The researchers noted that mature survival data were not available at 4 years follow-up, and there was no statistical difference in overall survival in either the full study population or in patients with stage III disease. Moreover, stage II patients showed no statistical difference in disease-free survival, although a trend favored the treatment arm, 85.1% vs 81.3%.
The incidence of grade 3-4 adverse events in the MOSAIC study was more than double in the Eloxatin group, compared with the control patients: 70% vs 31%. The most common grade 3-4 events were granulocytopenia, paresthesia, diarrhea, vomiting, and nausea. "Paresthesia was seen in 92% of patients on the Eloxatin combination; 21% had residual paresthesia at 18-month follow-up," Sanofi-Synthelabo said. "Three percent and 0.5% had grade 2-3 paresthesias, respectively, at 18-month follow-up.
Grade 3 and 4 hypersensitivity was noted in 3% and may require discontinuation of therapy, the company said. Hepatotoxicity evidenced by increase in transaminases (57% vs 34%) and alkaline phosphatases (42% vs 20%) was observed more commonly in the Eloxatin arm. Anaphylactic-like reactions to Eloxatin may occur within minutes after administration of the drug, and its labeling states that the drug should be infused only under the supervision of a qualified physician. In its letter to Sanofi-Synthelabo, the FDA also added immunoallergic hemolytic anemia and colitis (including Clostridium difficile diarrhea) to the list of adverse reactions associated with Eloxatin.