A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: Gemcitabine alone versus gemcitabine combined with cisplatin

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.