Two New Lung Cancer Studies Test Irinotecan Plus Gemcitabine

TAMPA, Florida—Irinotecan (Camptosar)/gemcitabine (Gemzar) combinations are being studied in two lung cancer trials. Caio Max S. Rocha Lima, MD, assistant professor of medicine at the University of South Florida’s H. Lee Moffitt Cancer Center in Tampa, Florida, presented overviews of the protocols.

Dr. Rocha Lima first described Cancer and Leukemia Group B (CALGB) trial 39809, an ongoing phase II randomized study of gemcitabine/irinotecan and gemcitabine/docetaxel (Taxotere) in previously untreated non-small-cell lung cancer. The primary objective of this trial was to determine the response rates of the two arms. Secondary objectives included assessing overall and failure-free survival, duration of complete remissions, and toxicity. Efficacy results are pending the completion of a median of 4 cycles of chemotherapy, but Dr. Rocha Lima presented preliminary toxicity data.

"This trial was open to patients with histologically or cytologically documented non-small-cell lung cancer who had measurable or evaluable disease, Performance status 0 to 1, no prior chemotherapy, and no radiation therapy more recently than 2 weeks before study entry," Dr. Rocha Lima said.

The protocol called for accrual of 36 patients per arm, which provided a 90% power to differentiate between 20% and 40% response rates. Patients were stratified according to stage, presence of central nervous system metastasis, and recurrent vs newly diagnosed disease.

Comparable Toxicities

"Eighty patients have been enrolled, and we have preliminary analysis based on the first 64 patients, 63 of whom met eligibility requirements, and a median of two cycles of therapy," Dr. Rocha Lima said. Twenty percent of patients in each arm had brain metastases.

Grade 3 and 4 hematologic toxicities were comparable between the two regimens. Grade 3 and 4 nonhematologic toxicities were uncommon and incomparable in both arms except for nausea and vomiting. "Grade 3 diarrhea occurred in 10% of patients on gemcitabine/irinotecan and in 7% of patients on gemcitabine/docetaxel, but it is notable that there was no grade 4 diarrhea in either arm," Dr. Rocha Lima said. There was one early death on each arm of the study.

Second-Line Treatment

Dr. Rocha Lima is also conducting a phase II trial of gemcitabine/irinotecan as second-line treatment for small-cell lung cancer (CALGB 39902). "The rationale for this study is that activity of irinotecan on a weekly schedule in previously treated small-cell lung cancer patients is in the same range as or even superior to that of topotecan (Hycamtin). Activity of gemcitabine in previously treated patients is modest but clinically relevant, and preclinical data suggest synergism for the combination," he said.

The trial is open to patients with either relapsed or refractory small-cell lung cancer who have had one previous chemotherapy or chemoradiotherapy regimen. The primary objective is to determine the response rates in previously treated small-cell lung cancer patients. Secondary endpoints are overall and failure-free survival, response duration, and toxicity.

"Sixteen patients have been accrued to each group (relapsed vs refractory patients) in the first stage of the study," Dr. Rocha Lima said. "Since activity has been observed in both treatment groups, further accrual continues to a target of 33 patients per group."