CHARLESTON, South CarolinaHighly censored data
from a multicenter phase II trial of irinotecan (Camptosar)/gemcitabine
(Gemzar) suggest that this combination, known as IrinoGem, is
well tolerated and active in advanced and metastatic pancreatic
cancer, Caio Max S. Rocha Lima, MD, reported at a clinical
investigators workshop. IrinoGem is now being compared to
gemcitabine alone in an international multicenter phase III
randomized trial involving 75 institutions and 350 patients with
locally advanced or metastatic pancreatic adenocarcinoma.
Irinotecan and gemcitabine are also potent radiation
sensitizers, and clinical trials exploring IrinoGem plus radiation
therapy in patients with advanced pancreatic cancer are also
warranted, Dr. Rocha Lima told participants of the workshop,
sponsored by the University of Texas
M. D. Anderson Cancer Center and Pharmacia Oncology. Dr. Rocha Lima
is Assistant Professor of Medicine at the Medical University of South
Carolina in Charleston, South Carolina.
Each drug is active as a single agent in a variety of solid tumors
and produces similar response rates and median survivals in advanced
and metastatic pancreatic cancer. The agents have complementary
rather than overlapping toxicity and showed synergy in preclinical
studies, Dr. Rocha Lima reported.
In the phase I study of irinotecan/gemcitabine in solid tumors,
maximum tolerated doses were 100 mg/m² of irinotecan and 1,000
mg/m² of gemcitabine. Both drugs were given on days 1 and 8
every 3 weeks. This permitted a potential for 100% of single-agent
irinotecan dose intensity and 80% of single-agent gemcitabine dose
intensity and avoided day 15 treatment. That day is associated with
frequent dose omissions/reductions on previously tested weekly
gemcitabine combinations. There were three partial responses in the
phase I trial.
Phase II Results
Based on the promising phase I data, Dr. Rocha Lima and colleagues
conducted a phase II study in 45 patients with previously untreated
advanced and metastatic pancreatic cancer. The two drugs were again
given on days 1 and 8, with the cycle repeating on day 21.
administered totaled 394, with 89% dose intensity for irinotecan and
87% for gemcitabine. There was modest toxicity with no toxic
deaths, Dr. Rocha Lima said. There was no grade 4 diarrhea, but
grade 3 diarrhea occurred in 6.7% of patients. Grade 4 neutropenia
occurred in 2.2% of patients. There was no febrile neutropenia, but
grade 3 neutropenia occurred in 15.6% of patients.
Overall response rate was 20%. CA19 levels dropped by more than half
in 38% of patients. Time to treatment failure was 2.8 months, and
median survival was 6.0 months (range 0.3 to 15.5 months) (see
Figure). This combination is well tolerated and active in
metastatic pancreatic cancer. The ongoing phase III trial will help
define the role of IrinoGem in pancreas cancer, Dr. Rocha Lima