Mar. 4, 2008 The addition of the drug gemcitabine with chemoradiation for the treatment of patients who had surgery for pancreatic cancer was associated with a survival benefit, although this improvement was not statistically significant, according to a study in the March 5 issue of JAMA.
Despite the potential benefits of surgically removing cancer involving the pancreas, there is a 50 percent to 85 percent rate of local relapse associated with liver and intra-abdominal failure and a 5-year survival of less than 20 percent, according to background information in the article. The frequency and pattern of failure makes the combination of added postoperative chemotherapy and radiation an important consideration. The drug gemcitabine has been shown to improve outcomes compared with the drug fluorouracil.
William F. Regine, M.D., of the University of Maryland Medical Center, Baltimore, and colleagues conducted a study to assess if the addition of gemcitabine to the supplemental treatment of fluorouracil chemoradiation (chemotherapy plus radiation) improved survival for patients who had a portion of their pancreas removed as a treatment for pancreatic cancer (surgical resection).
The randomized controlled phase 3 trial included 451 patients enrolled between July 1998 and July 2002 at 164 U.S. and Canadian institutions, with follow-up through August 2006. Patients received chemotherapy with either fluorouracil (n = 230) or gemcitabine (n = 221) for three weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy (with fluorouracil).
The researchers found that patients with pancreatic head (a part of the pancreas) tumors (n = 388) had a median (midpoint) survival of 20.5 months and 3-year survival of 31 percent in the gemcitabine group vs. 16.9 months and 22 percent in the fluorouracil group. A certain level of hematologic (involving abnormalities in the blood cell counts) toxicity (grade 4) was 1 percent in the fluorouracil group and 14 percent in the gemcitabine group without a difference in neutropenia (a blood disorder) or infection. There were no differences in the ability to complete chemotherapy or radiation therapy.
"The addition of gemcitabine to [supplemental] fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant," the authors write.
Patients in the study had the lowest rate of cancer recurring in its original location than in other previous studies. The tumor came back in the same area in 23 percent of the patients, compared to 40 percent to 60 percent of patients in other studies. At least 70 percent of the patients in this study experienced spread of their cancer to other parts of the body, a process that is known as systemic metastasis.
"Laboratory correlative studies from [this trial] are ongoing and are evaluating molecular genetic alterations that promote local and systemic relapse. Future trials should emphasize novel systemic treatments to reduce systemic metastases and modern image-guided radiation to prevent local recurrence while reducing radiation-related toxic effects."
Journal reference: JAMA. 2008;299:1019-1026.
Editorial: Adjuvant Therapy for Surgically Resected Pancreatic Adenocarcinoma
In an accompanying editorial, James L. Abbruzzese, M.D., of the University of Texas M. D. Anderson Cancer Center, Houston, offers suggestions on how to improve outcomes for pancreatic cancer patients with surgical resection.
"First, the lessons regarding the optimal selection of patients for surgical resection need to be exported more effectively into the high-surgical volume setting. ... Second, further work is needed to determine which patients are most likely to benefit from chemoradiation and, if this modality is going to evolve, further emphasis should be placed on the development of more effective radiation sensitizers."
"Third, based on interindividual differences in drug metabolism and DNA repair, it appears that patients who are more likely to benefit from current chemotherapy and chemoradiation strategies can be defined prospectively. These individualized approaches should be examined in prospective clinical trials.
Finally, and most importantly, efforts must be redoubled to develop a new generation of promising therapeutics, and the commitment must be increased to understand and test them in prospectively defined patient subsets--not the means to detect marginal or incremental improvements in clinical trials of large numbers of unselected patients."
Reference for editorial: JAMA. 2008;299:1066-1067.
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