NEW YORK (Reuters Health) – After resection of pancreatic adenocarcinoma, chemotherapy with fluorouracil or gemcitabine reduces mortality by about a third, Taiwanese researchers have shown.
On the other hand, they report, “Chemoradiation alone has little benefit, and chemoradiation plus chemotherapy is less effective in prolonging survival and more toxic than chemotherapy.”
Dr. Yu-Kang Tu, with the National Taiwan University in Taipei City, and colleagues point out in their paper in The Lancet Oncology online September 12, that pancreatic adenocarcinoma is the most lethal of cancers with a 5-year survival rate of less than 5%. While adjuvant treatments aimed at prolonging survival have been advocated, the optimum regimen is unclear.
They therefore conducted a meta-analysis of nine trials of five major adjuvant treatments — fluorouracil, gemcitabine, chemoradiation (i.e., radiation with fluorouracil as a radiosensitizer), chemoradiation plus fluorouracil and chemoradiation plus gemcitabine. Since head-to-head comparisons were not available for all treatments, the team used Bayesian network analysis to determine indirect comparisons using a common comparator.
They found that, compared to observation only, the mortality hazard ratios were 0.62 for fluorouracil, 0.68 for gemcitabine, 0.91 for chemoradiation, 0.54 for chemoradiation plus fluorouracil and 0.44 for chemoradiation plus gemcitabine.
However, positive lymph node status was associated with poorer survival. After adjustment for this, the authors report, “fluorouracil (HR 0.65) and gemcitabine (HR 0.59) provided an overall survival benefit over observation alone, whereas chemoradiation was associated with poorer overall survival compared with fluorouracil (HR 1.69) and gemcitabine (HR 1.86).”
Furthermore, chemoradiation plus fluorouracil or gemcitabine did not provide a survival advantage over fluorouracil or gemcitabine, according to the analysis.
Regarding side effects, the least toxicity was associated with chemoradiation followed by gemcitabine and fluorouracil; next was chemoradiation plus fluorouracil, and the most toxic was chemoradiation plus gemcitabine.
Gemcitabine and fluorouracil “were more favourable in terms of the balance between treatment benefit and harm,” Dr. Tu and colleagues comment.
Summing up, they conclude, “Our results suggest that adjuvant chemotherapy with fluorouracil or gemcitabine provides an overall survival advantage over observation or chemoradiation, whereas adding chemoradiation to chemotherapy provides little further survival benefit, but increases toxic effects.”
SOURCE: Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis
Lancet Oncol 2013.
