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Irinotecan/Gemcitabine Plus Radiation Tested in Locally Advanced Pancreatic Cancer

Irinotecan/Gemcitabine Plus Radiation Tested in Locally Advanced Pancreatic Cancer

WINSTON-SALEM, North Carolina—Preliminary data from a phase II trial of
induction irinotecan (Camptosar)/gemcitabine (Gemzar) followed by twice-weekly
gemcitabine and radiation in patients with locally advanced pancreatic cancer
show partial responses in 2 of 7 evaluable patients. There were no local
progressions, and median time to progression of 6 months, according to A.
William Blackstock, MD. Dr. Blackstock is assistant professor at Wake Forest
University, Winston-Salem, North Carolina, and at the University of North
Carolina at Chapel Hill.

"Today pancreatic cancer is essentially a lethal diagnosis," Dr.
Blackstock said. "With current approaches to chemoradiation for locally
advanced pancreatic cancer, the median survival of about 10 to 12 months is
about the best you can achieve. Until we develop more effective systemic
regimens, improving local tumor control is not likely to make a significant
difference." The phase II trial follows previous work showing single-agent
activity for gemcitabine and improved activity for gemcitabine plus radiation.

"A number of preclinical and clinical studies have suggested that a
twice-weekly dosing of gemcitabine with radiation is a better way to sensitize
than a weekly dosing schedule. In some phase I work, we determined that a
gemcitabine dose of 40 mg twice a week given with radiation was feasible. We
pursued this in Cancer and Leukemia Group B (CALGB) trial 89805. This study is
now closed after accruing 43 patients. While the median survival for
performance status 0 patients was 13.5 months, overall survival was 9.0 months;
only 4 patients had local failure as the initial site of failure. While I don’t
think these data are impressive, there was some inference that we improved
local control," Dr. Blackstock said.

Complementary Toxicity

The investigators added irinotecan to gemcitabine induction therapy because
the two drugs have complementary toxicity profiles, different mechanisms of
cytotoxicity, and overlapping antitumor activity in pancreatic cancer.
Preclinical studies also suggested synergy at concentrations of gemcitabine
above 0.1 µM and irinotecan above 3.2 µM.

Patients on the ongoing phase II trial are treated with irinotecan 100
mg/m²
and gemcitabine 1,000 mg/m² on days 1 and 8. This is followed by twice-weekly
gemcitabine at 40 mg/m² and radiation at 50.4 Gy. "We are using very
standard radiation doses and fractionation," Dr. Blackstock said.

The trial is enrolling patients with histologically or cytologically
confirmed nonmetastatic pancreatic cancer who have a life expectancy greater
than 6 months. Dr. Blackstock said that patients with regional (peripancreatic)
lymph node involvement are eligible. Study endpoints are time to progression,
local-regional control, and overall survival. The investigators will also
measure CA-19 responses and assess the predominant site of failure.

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