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DX-8951f/Gemcitabine Safe, Active in Advanced Solid Tumors

DX-8951f/Gemcitabine Safe, Active in Advanced Solid Tumors

NEW YORK—The combination of gemcitabine (Gemzar) and a potent, novel
topoisomerase-1 inhibitor similar to 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

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