Preliminary Analysis of Cancer and Leukemia Group B (CALGB) 80003: A Phase II trial of Gemcitabine, 5-Fluorouracil (5FU) and Radiation Therapy (RT) in Locally Advanced Non-Metastatic Pancreatic Adenocarcinoma.

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: October 18, 2005

Presenter: Harvey Mamon
Presenter's Affiliation: Dana Farber/Brigham and Women's Cancer Center, Boston, MA
Type of Session: Scientific

Background

The median survival for locally advanced, unresectable pancreatic cancer is quite low after chemotherapy and radiation (around 9 months).
GITSG trials from the 1980s showed a benefit to adding 5FU chemotherapy concurrently with radiation for this disease.
Gemcitabine chemotherapy has been shown to improve quality of life and survival in patients with locally advanced or metastatic disease.
Gemcitabine is a potent radiosensitizer.

Materials and Methods

81 patients were accrued from 26 institutions with locally advanced, unresectable pancreatic adenocarcinoma from November 2001 to October 2004.
All patients had laparoscopic or open confirmation of a lack of peritoneal carcinomatosis and liver metastases.
Patients received 50.4 Gy of external beam radiation therapy concurrently with continuous infusion 5FU (200mg/m2 5x week) and weekly gemcitabine (200mg/m2) followed by a three week break and then weekly gemcitabine (1000 mg/m2) given for 3 out of 4 weeks as a cycle, for a total of 4 cycles.
The primary endpoint is overall survival and secondary endpoints include clinical response, CA 19-9 response, time to progression and toxicity.

Results

78 patients are evaluable for this analysis.
67 patients have been followed for > 9 months.
Median follow-up is 10.5 months (2.9 to 37.7 months).
Toxicity data is available for 76 patients.
Median CA 19-9 was 402 (range 3-10,854)
For the 67 patients with > 9 month follow-up, 46 (69%) are alive.
Median overall survival is 12 months (95% CI from 9.9 to 14.3 months)
43% of patients had grade 3 or 4 neutropenia, 25% of patients had grade 3 nausea, and 16% of patients had grade 3 vomiting.

Author's Conclusions

Median overall survival was 12 months, and the study should be continued.
Toxicity was acceptable with this regimen.
This regimen appears promising and this is worthy of further investigation.

Clinical/Scientific Implications

The investigators should be commended for performing a well designed phase 2 trial to test the regimen including 5FU and Gemcitabine with radiation for unresectable pancreatic cancer. The analysis of this trial is preliminary, but it already appears that the combination of these two chemotherapeutic agents with radiation is well tolerated and at least as effective as the standard of care, 5FU with radiation. It will take a phase 3 randomized trial to test this regimen’s superiority, and data from this trial will help that study be designed. New chemotherapy agents have been exciting GI oncologists, because for the first time in many years there are a number of novel treatment strategies for aggressive, difficult to manage diseases. The addition of biologic/targeted agents may help continue to make incremental gains in pancreatic cancer treatment outcomes.