NEW YORKAn irinotecan(Drug information on irinotecan) (Camptosar) plus gemcitabine(Drug information on gemcitabine) (Gemzar) combination known as IrinoGem was associated with low toxicity, median survival of 6 months, and a 1-year survival rate of 27%, according to results from a phase II study presented at the Chemotherapy Foundation Symposium XVIII.
"IrinoGem is active and well-tolerated in advanced and metastatic pancreatic cancer," said Caio Max S. Rocha Lima, MD, assistant professor of medicine, Medical University of South Carolina, Charleston.
Both gemcitabine and irinotecan are active in a number of solid tumors, and preclinical data suggest they are synergistic in combination, he added.
Dr. Rocha Lima updated results of his group’s first experience with the IrinoGem regimen, developed at the Medical University of South Carolina. The data come from a single-arm, eight-center, nonrandomized phase II trial first presented at the American Society of Clinical Oncology 2000 meeting in New Orleans (abstract 1043).
The phase II study included 45 chemotherapy-naïve patients with locally advanced and metastatic pancreatic cancer. Three of the patients had prior radiation therapy.
Patients were treated with gemcitabine 1,000 mg/m2 IV over 30 minutes, followed by irinotecan 100 mg/m2 IV over 90 minutes on days 1 and 8 of a 21-day cycle. A total of 394 treatment cycles were administered. Full doses of gemcitabine were delivered in 87% of patients and full doses of irinotecan in 89%.
Limited Adverse Events
Modest toxicity was noted (see table at left). There were no toxic deaths or cases of neutropenic fever. "To our surprise, only 6.7% of patients experienced grade 3 diarrhea, and there was no grade 4 diarrhea," Dr. Rocha Lima said. "I strongly believe that the good tolerance of IrinoGem is due to the dosing schedule avoiding the days 15 and 22 administration of irinotecan used in other trials."
Efficacy results included an overall objective response in 9 patients (20%), a median survival of 6 months (range, 0.3 to 15.5 months), and a median time to treatment failure of 2.8 months (range, 0.1 to 11.3 months). The 1-year survival rate was 27.5%.
A drop in CA-19 of more than 50% was seen in 17 of 40 patients (38%) who had elevated CA-19 at baseline.
Based on those findings, a comparative trial of IrinoGem vs single-agent gem-citabine in metastatic pancreatic cancer has been launched, Dr. Rocha Lima said. The study is being conducted at 75 centers, and at least 65 patients have been enrolled.
The study will compare the same IrinoGem dosage regimen used in the phase II trial with gemcitabine 1,000 mg/m2 weekly for 7 weeks, followed by 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle.
Furthermore, the "easy tolerability" and ability to give high doses of both agents in this combination may allow for a third agent to be added. Several recent studies are underway or planned.