Medline ® Abstracts for References 43-45
Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head.
Heinrich S, Pestalozzi BC, Schäfer M, Weber A, Bauerfeind P, Knuth A, Clavien PA
J Clin Oncol. 2008;26(15):2526.
PURPOSE: To test the safety of neoadjuvant chemotherapy for resectable pancreatic cancer.
PATIENTS AND METHODS: Patients with cytologically proven resectable adenocarcinoma of the pancreatic head were eligible for this prospective phase II trial. After confirmation of resectability by contrast-enhanced computed tomography (ceCT), positron emission tomography/CT, laparoscopy, and endoscopic ultrasound, patients received four biweekly cycles of gemcitabine 1,000 mg/m(2) and cisplatin 50 mg/m(2). Thereafter, staging was repeated and patients underwent surgery. Quality of life (QoL) and prealbumin serum levels were determined pre- and postchemotherapy. Follow-up included 3-month CA 19-9 measurements and ceCT after 6, 12, 18, and 24 months. Histologic tumor response was assessed by two scoring systems.
RESULTS: Twenty-eight patients entered this study. Adverse effects were mainly gastrointestinal and hematologic, most often mild, and never of grade 4. Twenty-six patients (93%) had resectable cancer on restaging examinations, and the R0 resection rate was 80%. Histologic tumor response and cytopathic effects were documented in 54% and 83% of patients, respectively. On intention-to-treat analysis, disease-free and overall survival were 9.2 months (95% CI, 5.6 to 12.9 months) and 26.5 months (95% CI, 11.4 to 41.5 months) and 9 months (95% CI, 6.99 to 10.1 months) and 19.1 months (95% CI, 15 to 23.1 months) for ductal adenocarcinoma, respectively. QoL improved in two items and was unchanged in all other items. Moreover, prealbumin serum levels significantly improved during chemotherapy (P = .008). CONCLUSION Neoadjuvant chemotherapy with gemcitabine and cisplatin is well tolerated and does not impair resectability of pancreatic cancer. Furthermore, it improves the QoL and the nutritional status of affected patients with favorable overall and disease-free survival.
Department of Visceral and Transplantation Surgery, Institute of Surgical Pathology, Swiss Hepato-Pancreato-Biliary Center, Zurich, Switzerland
A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin.
Palmer DH, Stocken DD, Hewitt H, Markham CE, Hassan AB, Johnson PJ, Buckels JA, Bramhall SR
Ann Surg Oncol. 2007;14(7):2088. Epub 2007 Apr 24.
BACKGROUND: Survival after surgery for pancreas cancer remains low. This improves with adjuvant chemotherapy, but up to 30% patients do not receive the prescribed treatment. Neoadjuvant therapy may increase the proportion of patients who receive all treatment components, may downstage disease before surgery, and may provide early treatment of micrometastases. This randomized phase 2 study compares gemcitabine-based chemotherapy regimens to identify the most promising regimen for future study.
METHODS: Fifty patients with potentially resectable pancreas lesions were enrolled onto the study. Twenty-four patients were randomized to gemcitabine (1000 mg/m(2)) every 7 days for 43 days; 26 patients were randomized to gemcitabine (1000 mg/m(2)) and cisplatin (25 mg/m(2)), 7 to the original schedule (omitting day 22) and 19 to a revised schedule due to neutropenia (omitting days 15 and 36). The primary outcome measure was resection rate.
RESULTS: Patients who were allocated to gemcitabine received a median of 85% of the planned dose. Patients who were allocated to combination treatment received a median of 88% and 92% of the planned gemcitabine and cisplatin doses, respectively. There were 10 episodes of grade III/IV hematological toxicity in each group. Twenty-seven patients (54%) underwent pancreatic resection, 9 (38%) in the gemcitabine arm and 18 (70%) in the combination arm, with no increase in surgical complications. To date, 34 patients (68%) have died. Twelve-month survival for the gemcitabine and combination groups was 42% and 62%.
CONCLUSIONS: Chemotherapy can be safely administered before pancreatic surgery. Combination therapy with gemcitabine and cisplatin is associated with a high resection rate and an encouraging survival rate, suggesting that further study is warranted.
Cancer Research UK Institute for Cancer Studies and Clinical Trials Unit, University of Birmingham, Vincent Drive, Birmingham, B15 2TT, United Kingdom. Daniel.Palmer@uhb.nhs.uk
MacKenzie S, Zeh H, McCahill LE, et al. A pilot phase II multicenter study of nab-paclitaxel and gemcitabine as preoperative therapy for potentially resectable pancreatic cancer (PC). (abstract). J Clin Oncol 31, 2013 (suppl abstr 4038). http://meetinglibrary.asco.org/content/111497-132 (Accessed on March 24, 2014).
no abstract available