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Irinotecan, Cisplatin, and Radiotherapy Tested in Esophageal Cancer

Irinotecan, Cisplatin, and Radiotherapy Tested in Esophageal Cancer

NEW YORK—Esophageal cancer, though relatively rare in the United States,
is deadly, with a 90% mortality for patients treated with conventional therapy.
David H. Ilson, MD, PhD, assistant attending physician at Memorial
Sloan-Kettering Cancer Center in New York City, described new multimodal
attempts to improve these outcomes.

A US Intergroup study (INT-113) showed no advantage to adding five cycles of
5-fluorouracil (5-FU) plus cisplatin (Platinol) before surgery in treating
locally advanced disease. Dr. Ilson said that a recent, larger trial from the
United Kingdom reported an advantage to two cycles of 5-FU/cisplatin prior to
surgery, but the median and 2-year survival were no better than survival with
surgery alone in the Intergroup trial. "Most of us have focused on
concurrent radiation and chemotherapy, with or without surgery, as the strategy
to pursue in future studies," he said.

Trials of preoperative chemoradiation have reported pathologic complete
responses in 20% to 40% of patients, with 5-year disease-free survivals of 25%
to 35%. "These regimens can have substantial toxicity, particularly with
infusional 5-FU and cisplatin. Because of the poor survival and the toxicity of currently available
therapy we need to look at new agents," Dr. Ilson said.

Irinotecan is Radiosensitizer

Irinotecan (Camptosar) is attractive in this regard because cell lines and
xenografts show that it is a radiosensitizer. Dr. Ilson said that the mechanism
of radiosensitization might be increased recruitment of cells into the G2/M
phase, the most radiosensitive part of the cell cycle. Irinotecan, a
topoisomerase inhibitor, also might enhance lethal double-strand DNA breaks.

Phase I lung cancer trials done in Japan suggested that combining
irinotecan, cisplatin, and radiotherapy was feasible. Recent studies of
irinotecan-based therapy in esophageal and gastric cancers reported a
single-agent response rate of 15% and combination response rates of about 50%
to 60%.

A phase I trial of weekly irinotecan (65 mg/m²) and cisplatin (30 mg/m²) on
a 4-week-on, 2-week-off schedule conducted at Memorial Sloan-Kettering Cancer
Center caused minimal toxicity and was associated with responses in esophageal
and gastrointestinal (GI) cancers.


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