NEW YORKThe combination of gemcitabine(Drug information on gemcitabine) (Gemzar) and a potent, novel topoisomerase-1 inhibitor similar to irinotecan(Drug information on irinotecan) (Camptosar) is safe, has predictable toxicities, and has demonstrated significant antitumor activity in a variety of solid malignancies, according to results of a 70-patient phase I/pharmacokinetic study.
The agent, known as DX-8951f, or exatecan mesylate (Daiichi Pharmaceutical Corp.), is structurally related to irinotecan and is approximately 3 to 10 times more potent than the active metabolite of irinotecan, SN-38, Eileen O’Reilly, MD, said at the Chemotherapy Foundation Symposium XIX. Dr. O’Reilly is assistant attending physician, GI Oncology Service, Memorial Sloan-Kettering Cancer Center.
Not a Prodrug
"Exatecan differs from irinotecan in that it is not a prodrug, so it doesn’t need to be metabolized for activation, and it has greater in vitro potency," she said.
The investigators chose to combine exatecan with gemcitabine because they both have a broad spectrum of activity, and their toxicity profiles are "relatively nonoverlapping," Dr. O’Reilly said. Also, in vitro studies suggest that the two have additive, if not synergistic, effects in pancreatic and other tumor cell lines.
As a single agent, exatecan has, in phase I studies, shown antitumor activity in small-cell lung cancer, sarcoma, bladder cancer, colon cancer, and other cancers. A 39-patient phase II trial presented at ASCO 2001 (San Francisco) showed that the agent was active in advanced pancreatic cancer, with a median survival of 10.8 months and 4.2 months, respectively, for untreated and pretreated patients.
70 Patients Enrolled