Phase I/II trial of induction chemotherapy followed by concurrent chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer.

BACKGROUND: We used a novel combination of induction chemotherapy with gemcitabine (GEM) and cisplatin (CDDP), followed by concurrent chemoradiotherapy (CCRT) with the same agents in patients with locoregionally advanced pancreatic cancer. Surgery or additional chemotherapy followed on the basis of response.
METHODS: Patients with borderline resectable or locally advanced pancreatic cancer received induction weekly with GEM (1000 mg/m(2)) or CDDP (30 g/m(2)). Patients without progression of disease then underwent surgery or CCRT, including four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy. After CCRT, patients deemed resectable underwent surgery; patients with disease that remained unresectable and that did not progress received additional GEM/CDDP for 2 months.
RESULTS: A mean 76% of intended GEM dose and 75% of CDDP dose was delivered during induction (n = 26). There were three incidences of grade 4 toxicity (fever or neutropenia). After induction, five patients progressed and one patient underwent resection. Eighteen patients received CCRT, and three patients underwent resection. After CCRT, disease of 10 patients progressed, and in 5 patients, it remained unresectable without progression, and the patient received additional GEM/CDDP. Dose-limiting toxicity was at dose level IV (thrombocytopenia). Median overall and disease-specific survival was 13 months.
CONCLUSION: GEM/CDDP induction chemotherapy followed by CCRT is well tolerated and rendered the disease of 4 of 26 patients resectable in this study. The recommended phase II dose for GEM and CDDP in combination with full-dose radiotherapy (5040 cGy) is 300 mg/m(2) and 10 mg/m(2) weekly for 5 weeks. Median survival in this group was 13 months. This neoadjuvant combined modality approach is both feasible and active; further studies are warranted.