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Four-Drug Regimen Promising in Cancer of Pancreas, Gallbladder

Four-Drug Regimen Promising in Cancer of Pancreas, Gallbladder

NEW YORK—Dose escalation of irinotecan (Camptosar) is continuing in a
phase I trial of a four-drug regimen that has shown encouraging activity in
patients with pancreatic and gallbladder cancer, according to a report at the
Mount Sinai School of Medicine Chemotherapy Foundation Symposium XX.

The regimen adds irinotecan to a previously tested three-drug protocol,
reported Peter Kozuch, MD, assistant professor of clinical medicine, Columbia
University College of Physicians and Surgeons, and Department of
Hematology-Oncology, St. Luke’s Roosevelt Hospital Center. Known by the
acronym G-FLIP, the regimen includes gemcitabine (Gemzar), fluorouracil
(5-FU)/leucovorin, irinotecan, and cisplatin (Platinol).

Between March and September, 2002, 14 patients were enrolled in the phase
I trial of G-FLIP, eight with pancreatic cancer, five with gallbladder
cancer, and one with squamous cell carcinoma of the head and neck. Ages of
the patients ranged from 45 to 78 years (median, 62.4). Four had received
previous chemotherapy.

Of the 10 patients evaluable after four cycles of therapy, Dr. Kozuch
reported, one with pancreatic cancer attained a complete response. Partial
responses occurred in three patients, two with gallbladder cancer and one
with pancreatic cancer. Disease stabilization of at least 8 weeks was seen in
two pancreatic cancer patients. "The median duration of response," Dr. Kozuch
said, "has not been defined, with a median follow-up of 10.6 weeks."

The outpatient administration of G-FLIP begins with infusion of 500 mg/m2
of gemcitabine given at a rate of 10 mg/m2 per minute, for a total of 50
minutes. This is followed by administration of irinotecan according to the
dose-escalation schedule, Dr. Kozuch said. Doses start at 80 mg/m2 and
increase stepwise by 20 mg/m2.

Next in the drug sequence is 300 mg of leucovorin. This is followed by a
400 mg/m2 bolus of 5-FU. Patients are then sent home with a portable pump to
receive 1,500 mg/m2 of 5-FU over the next 24 hours. "They return to the
infusion suite on day 2 for cisplatin and vigorous hydration with saline and
mannitol," Dr. Kozuch said. The cisplatin dose is 35
mg/m2. Treatment cycles are scheduled for every 2 weeks.

"The G-FLIP program was designed to exploit sequence-dependent synergistic
activity between drugs while minimizing sequence-dependent toxicity," Dr.
Kozuch said. In vitro, he noted, preceding cisplatin with 5-FU maximizes
synergistic activity. If irinotecan is given before 5-FU, he added, less
diarrhea and neutropenia occurs.


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