PEAPACK, New JerseyPotential directions for irinotecan
(Camptosar) clinical research in the future and for the application of novel
therapeutics were presented by Langdon Miller, MD, of Pharmacia Oncology
Development in Peapack, New Jersey.
"The developmental objective in colorectal cancer is to
improve the therapeutic index in metastatic disease. This will include
developing new schedules for treatment of older patients, diarrhea control, and
pharmacogenomically directed therapy," Dr. Miller said.
In addition, new agents are being tested for their activity
against colorectal and other forms of cancer. These agents include celecoxib
(Celebrex), SU-5416, and C225. "From our foundation in colorectal cancer
(Figure 1), we see these novel therapeutics standing on the shoulders of
irinotecan-based therapy for metastatic and adjuvant treatment," Dr.
Miller said. "Celecoxib in particular has the prospect of extending our
reach into the exciting area of cancer prevention."
Use in Older Patients
Dr. Miller said that first-line use of irinotecan/fluorouracil
(5-FU)/leucovorin is highly age-dependent, with only 35% of eligible patients
over age 65 receiving treatment. Pharmacia researchers retrospectively analyzed
data with respect to age and found no age-related differences in time to
progression or in survival.
Diarrhea was slightly but not dramatically more common in the
older patients, as was neutropenia. "Older patients may be a little more
sensitive to toxicity, but dosage modification takes care of these
problems," Dr. Miller said.
Researchers will also be evaluating a new schedule that
includes irinotecan/5-FU/leucovorin on weeks 1 and 2 every 3 weeks.
Dr. Miller said that diarrhea prevention agents of primary
interest are celecoxib and thalidomide (Thalomid). A diarrhea prevention study
of thalidomide is being developed.
Other studies will evaluate the survival benefits of the
experimental agent SU-5416 in patients with first-line metastatic colorectal
cancer. In one trial, patients will receive irinotecan/5-FU/leucovorin and then
be randomized to receive or not receive SU-5416. In the other trial, patients
will receive 5-FU/leucovorin with or without SU-5416.
Dr. Miller also reported that a celecoxib adjuvant study is
planned for patients with high-risk stage III colorectal cancer.
Studies in other cancers include irinotecan in first-line
therapy of pancreatic, gastric, and small-cell lung cancer.
Two phase III trials-one ongoing and one planned-test
different schedules of cisplatin (Platinol)/irinotecan in patients with
small-cell lung cancer. Pharmacia Oncology Development is conducting the
ongoing trial and the Southwest Oncology Group (SWOG) is planning the other
A gemcitabine (Gemzar)/irinotecan combination therapy has been
studied in a phase II trial in pancreatic cancer, and researchers have
correlated response with levels of CA 19-9. "There appears to be an
amazing correlation between CA 19-9 response and tumor response," Dr.
Based on the phase II results, a phase III study of
gemcitabine/irinotecan is now ongoing. "We hope that CA 19-9 can become an
accepted study endpoint if it works out in this phase III trial," Dr.