A Phase II Study of Gemzar, Taxotere, and Xeloda (GTX) for Adjuvant Pancreatic Cancer
The adjuvant treatment of resected pancreatic cancer is currently in flux. Many in the
United States continue to use 5FU-based chemotherapy with radiation to the pancreatic bed.
Some in the States, and most investigators in Europe, use a 5FU based chemotherapy-alone
approach, based on the ESPAC-1 data. Many investigators believe that since gemcitabine is a
more active drug in the metastatic setting, it should be moved "up front" in the adjuvant
treatment of pancreatic cancer patients. At Columbia, we offer gemcitabine-based treatments
with discussions with patients regarding risks, benefits, and limitations in current
knowledge. We have usually offered radiation to those with positive margins, and
chemotherapy alone to those without. Based on the early studies using gemcitabine, we
believe that this will ultimately prove to be a more effective adjuvant drug than 5FU. Some
patients have asked for GTX in the adjuvant setting as well, prompting the creation of this
trial. Because of concerns about increased toxicity of this regimen, determination of
patient safety will be the primary objective of this study, through careful monitoring of
adverse events. This trial will be a chemotherapy-only study, offered to those with clean
margins of resection.
Taxotere administered "weekly" has activity in a variety of tumor types including breast,
lung, ovarian and prostate cancer. Patients with advanced breast cancer, including some who
had previously been treated with paclitaxel or anthracyclines, have responded to the weekly
administration of Taxotere. The recommended dose of weekly Taxotere is 30-40 mg/m2/week for
6 out of 8 weeks. The same dose intensity can be achieved on a 3 out of 4 week basis.
However, this protocol will give drugs 2 out of every 3 weeks, thus dose intensity is less.
Weekly administration of Taxotere is well tolerated and produces substantially less
myelosuppression than is observed with standard Taxotere administration every 3 weeks.
Acute toxicities are uncommon, as is peripheral neuropathy. Prolonged treatment with weekly
Taxotere, may result in chronic toxicities (including, asthenia (fatigue), anemia, edema,
excessive lacrimation (epiphora), and onycholysis). Chronic toxicities are most prominent
when Taxotere is administered on a continuous weekly basis, i.e., without a break, and are
delayed in onset by providing breaks in treatment (for example, treating 6 out of 8 weeks or
3 out of 4 weeks); these chronic toxicities occur at a lower cumulative dose when a
continuous weekly schedule of Taxotere is utilized.
Premedication with dexamethasone is recommended for all patients receiving weekly Taxotere
therapy to reduce the incidence and severity of fluid retention as well as the severity of
hypersensitivity reactions. A variety of dexamethasone schedules have been used in studies
with weekly Taxotere. Dexamethasone 4 to 8 mg x 3 doses taken orally the night before, the
morning of, and the evening after Taxotere administration appears to be an effective
schedule. We have found that a single low dose of 10 mg IV before the Taxotere usually
prevents anaphylaxis and the pedal edema associated with this drug.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety of the GTX regimen in patients with resected pancreatic cancer, using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
At days 4, 11, and follow-up.
Robert L Fine, MD
United States: Institutional Review Board
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