NEW YORKThe combination of oxaliplatin(Drug information on oxaliplatin) (investigational) and irinotecan(Drug information on irinotecan) (Camptosar) as front-line treatment for colorectal cancer is feasible and potentially synergistic, preliminary data from an M.D. Anderson Cancer Center phase I/II trial suggests.
This is an important observation because it suggests a possible alternative to 5-fluorouracil (5-FU) in previously untreated patients if these patients can be identified as 5-FU resistant beforehand, said Paulo M. Hoff, MD, assistant professor of medicine, Department of Gastrointestinal Medical Oncology.
"We are finally entering an era where we may be able to identify patients who will not respond to 5-FU," Dr. Hoff said at the Chemotherapy Foundation Symposium XVIII, "and I think we should try to use our knowledge about new agents to come up with new regimens that will work more specifically for those patients, sparing them 5-FU toxicity."
Prior data from phase I and II studies have suggested this combination is active, but the study populations included patients with colorectal cancer refractory to 5-FU. For example, one phase II study of 36 such patients produced an overall response rate of 42% and median survival of more than 11 months.
In the phase I portion of the M.D. Anderson study, 14 patients refractory to 5-FU were treated at a fixed oxaliplatin dose of 130 mg/m2 (the dose traditionally used on an every-3-week schedule) and escalated irinotecan doses. The main toxicities observed were neutropenia, peripheral neuropathy, and diarrhea.
In the ongoing phase II study, both drugs are given on day 1 of a 21-day course. Oxaliplatin is given in a 120-minute IV infusion, immediately followed by irinotecan in a 30-minute infusion.
The phase II study is designed to determine objective response rates for oxaliplatin plus irinotecan in previously untreated subjects. Up to 54 patients will be recruited. The trial will be terminated early if four or fewer responses are seen among the first 19 patients enrolled; otherwise, at least 35 more patients will be enrolled.
Twelve previously untreated colorectal cancer patients had been enrolled as of Dr. Hoff’s presentation. The median age of these 12 patients was 57, and all had Zubrod performance status of 0, except for one with performance status of 1.
While it is still too early to evaluate six of these patients, there were two partial responses, two stable disease, and two progressions among the six evaluable patients.
"Obviously, these are very preliminary results," Dr. Hoff said. "Nevertheless, we are very excited to see this degree of response already. We feel, based on the data from Europe and our own data, that there is a good chance the drugs are synergistic, indeed as has been suggested in preclinical models."
Grade 1-2 toxicities were as expected and included nausea, vomiting, diarrhea, constipation, neutropenia, paresthesia/pain, alopecia, and fatigue. There were several grade 3-4 toxicities in the first cycle, including diarrhea (1 case), neutropenia (2 cases), and anemia (1 case).
"We feel this combination may be an alternative for patients who, in the future, will be determined to be resistant to 5-FU," Dr. Hoff said.