NEW YORKEsophageal 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(Drug information on 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(Drug information on 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.