Irinotecan Is a Candidate for Concurrent Chemoradiotherapy

NASHVILLE, Tennessee—Irinotecan (Camptosar) is a candidate for concurrent chemoradiotherapy to treat non-small-cell lung cancer (NSCLC) because it is synergistic with platinum and is a potent radiation sensitizer, reported Hak Choy, MD, professor of radiation oncology at the Vanderbilt-Ingram Cancer Center in Nashville. The irinotecan/platinum combination was shown to be active in NSCLC in phase II studies. A number of researchers are now working on refining irinotecan/radiotherapy approaches for NSCLC in phase I and phase II trials, Dr. Choy noted.

"Only 14% of all lung cancer patients will be alive 5 or more years after their diagnosis," Dr. Choy said. "Of the 178,000 new lung cancer cases in 1997, 151,000 were NSCLC. Most of these were in advanced stages at diagnosis and 5-year survival is very dismal for stage III disease, about 5% to 10%."

Studies of combined-modality therapy have shown that sequential chemoradiotherapy is better than radiation alone and that concurrent chemoradiotherapy is more effective than sequential chemotherapy and radiation, according to Dr. Choy. Along with irinotecan, new agents being studied for concurrent chemoradiotherapy include paclitaxel (Taxol), vinorelbine (Navelbine), gemcitabine (Gemzar), and docetaxel (Taxotere). "The question now is which drug is optimal for use in concurrent chemoradiotherapy," Dr. Choy said.

Irinotecan Study Results

"A phase I/II study of weekly irinotecan/radiotherapy for NSCLC done by Takeda et al in Japan reported a remarkable 76% response rate, 1-year survival of 61%, and 2-year survival of 38%, " Dr. Choy said. Median survival was 15.7 months, and the main dose-limiting toxicity in this study was pneumonitis. Patients were treated with irinotecan doses of 30 to 45 mg/m² and 60 Gy radiation.

A phase I study by Fukuda et al of irinotecan/cisplatin(Platinol)/radiotherapy reported a response rate of 65% and recommended phase II doses of this combination of irinotecan 60 mg/m² and cisplatin 80 mg/m². Radiation was given at 24 Gy plus a 26-36 Gy split course.

Toxicity Issues

Dr. Choy is co-chair of a phase I pilot study of irinotecan, carboplatin (Paraplatin), and radiation therapy for medically and/or surgically inoperable NSCLC now underway through the Vanderbilt Cancer Center Affiliate Network. He reported that 27 patients have been treated and that neutropenia had been the main dose-limiting toxicity. The maximum tolerated dose (MTD) of weekly irinotecan and carboplatin with radiation therapy was 30 mg/m² for irinotecan and carboplatin at an area under the concentration curve (AUC) of 2. The overall response rate thus far is 62%, and survival data are not yet available.

"Weekly irinotecan with or without platinum can be combined with radiation therapy as long as you stay below the 60 mg/m² dose level. So far, pulmonary toxicity has not been an issue with this combination," Dr. Choy said.

Irinotecan has also been combined with paclitaxel, carboplatin, and radiation, but Dr. Choy said this produced toxicity problems that limit this regimen’s usefulness.