Medline ® Abstracts for References 8,9
Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.
Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C, Stocken DD, Cunningham D, O'Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A, Lacaine F, Sand J, Izbicki JR, Mayerle J, Dervenis C, Oláh A, Butturini G, Lind PA, Middleton MR, Anthoney A, Sumpter K, Carter R, Büchler MW
J Clin Oncol. 2014;32(6):504. Epub 2014 Jan 13.
PURPOSE: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown.
PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy.
RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P<.001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P<.001).
CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.
Juan W. Valle, Derek O'Reilly, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust and University of Manchester, Manchester; Richard Jackson, Trevor Cox, John P. Neoptolemos, Paula Ghaneh, Charlotte L. Rawcliffe, Liverpool Cancer Research UK Centre and the National Institute for Health Research Pancreas Biomedical Research Unit, University of Liverpool, Liverpool; Daniel Palmer, the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust; Deborah D. Stocken, the Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham; David Cunningham, Royal Marsden Hospital Foundation Trust, Sutton; Mark R. Middleton, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford; Alan Anthoney, The Leeds Teaching Hospital Trust, Leeds; Kate Sumpter, Freeman Hospital, Newcastle upon Tyne; Ross Carter, Glasgow Royal Infirmary, Glasgow, United Kingdom; Claudio Bassi, Giovanni Butturini, University of Verona, Verona, Italy; Dav
Time to the initiation of adjuvant chemotherapy does not impact survival in patients with resected pancreatic cancer.
Mirkin KA, Greenleaf EK, Hollenbeak CS, Wong J
Cancer. 2016 Oct;122(19):2979-87.
BACKGROUND: Surgical resection with adjuvant chemotherapy is the standard of care for patients with pancreatic cancer, but to the authors' knowledge, little is known regarding the temporal relationship between chemotherapy initiation and survival. The current study analyzed the impact of time to the initiation of adjuvant chemotherapy.
METHODS: The National Cancer Data Base (2003-2011) was retrospectively reviewed for patients with clinical American Joint Committee on Cancer stages I to III resected pancreatic carcinoma. Time to chemotherapy was stratified at the 12-week postoperative time point. Univariate and multivariate analyses were performed.
RESULTS: The current study included 6706 patients who underwent surgical resection alone, 3723 patients who initiated adjuvant chemotherapy at≤12 weeks, and 669 patients who initiated adjuvant chemotherapy at>12 weeks. Patients who received chemotherapy at>12 weeks were older and had greater comorbidities. Those undergoing a Whipple resection or total pancreatectomy were more likely to initiate chemotherapy later compared with those patients undergoing a distal surgical resection. Adjuvant chemotherapy conferred a survival benefit over surgical resection alone (P<.0001). There was no overall survival benefit observed for patients receiving adjuvant chemotherapy at≤12 weeks compared with at>12 weeks (P =.5301). When stratified by pathological stage of disease, there was no survival benefit noted for the earlier initiation of chemotherapy: stage I: P =.2783; stage II: P =.0708; and stage III: P =.0778. After controlling for patient, disease, and surgery characteristics, both patients who initiated adjuvant chemotherapy at≤12 weeks and at>12 weeks were found to have a 35% lower odds of mortality versus those who underwent surgical resection alone (P<.0001 for both).
CONCLUSIONS: The earlier initiation of adjuvant chemotherapy does not appear to significantly impact long-term survival in patients with resected pancreatic cancer. Because adjuvant chemotherapy confers a survival benefit, delayed chemotherapy should be offered when appropriate. Cancer 2016;122:2979-2987.©2016 American Cancer Society.
Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.