NEW YORKThe combination of oxaliplatin (investigational) and
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
"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,
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
"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.