A Single-Arm, Nonrandomized Phase II Trial of Neoadjuvant Gemcitabine and Oxaliplatin in Patients With Resectable Pancreas Adenocarcinoma

Abstract

Objective The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined. We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma. Methods Eligible patients were screened using CT pancreas angiography, laparoscopy, endoscopic ultrasound and fine needle aspiration cytology, to identify 38 patients who received four cycles of neoadjuvant gemcitabine 1000mg/m2 IV over 100 minutes and oxaliplatin 80 mg/m2 IV over 2 hours, every 2 weeks. Patients whose tumors remained resectable at re-staging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m2 IV over 30 minutes day 1, 8, 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiologic, tumor marker and pathologic response to neoadjuvant therapy, time to recurrence, patterns of failure and feasibility of obtaining pre-operative core biopsies. Results Thirty-five of 38 (92%) patients completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%) of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% CI 17- NA) and the median disease-specific survival was 30.6 months (95% CI 19 - NA). Conclusion This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. NCT00536874.

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

“…100,[157][158][159] Well established ICD inducers include commonly employed anticancer chemotherapeutics such as: (1) (6) bortezomib, a proteasomal inhibitor approved for the therapy MM and mantle cell lymphoma (MCL); [171][172][173][174][175][176][177][178][179][180][181] (7) cyclophosphamide, a DNA-alkylating agent approved for use in patients with chronic myeloid leukemia (CML), AML, ALL, chronic lymphocytic leukemia, MM, ovarian carcinoma, breast carcinoma, mycosis fungoides, lymphoma, neuroblastoma, and retinoblastoma; 177,[182][183][184][185][186][187][188][189][190][191] and (8) oxaliplatin, a platinum-derivative licensed for the therapy of advanced colorectal carcinoma in combination with 5-fluorouracil and folinic acid. 156,157,[192][193][194][195][196][197][198] Moreover, there is some evidence that microtubule-targeting agents including taxanes and vinca alkaloids (which are commonly used for the treatment of multiple carcinomas) can stimulate ICD. 41,199 Along the lines of our Trial Watch series, here we discuss recent preclinical and clinical advances in the development of ICD-inducing chemotherapeutic regimens.…”

FOLFIRINOX induction therapy for stage III pancreatic adenocarcinoma

“…Our findings of a 20% ORR (without radiation) and a 29% ORR with selective radiation therapy are similar, and suggest that response to FOLFIRINOX may be superior to other reported regimens. The above ORRs display a consistent pattern, in which the ORR with FOLFIRINOX is at least two-fold higher compared to non-FOLFIRINOX regimens 1,4 . It should be noted however, that a high ORR(23%) was recently reported in stage IV PDAC patients in a phase III randomized trial that evaluated a novel regimen of nab-paclitaxel plus gemcitabine 21 .…”

“…Retrospective studies of patients with both borderline resectable PDAC (stage I-II) and stage III patients(locally unresectable) have also suggested an ORR of approximately 30% with FOLFIRINOX 2,3 . The reported ORR from non-FOLFIRINOX regimens has generally been in the range of 10%, including the results of a phase II study from our institution that demonstrated a 10% ORR for resectable patients treated with preoperative gemcitabine and oxaliplatin therapy 4 .…”

Neoadjuvant Therapy for Pancreatic Cancer

“…[37][38][39][40][41] Among those who underwent resection, 69% to 83% had R0 resection. No complete response was observed.…”

“…Another report 40 testing GemOx in 27 resected patients noted no mortality; benign fluid collections and infections were present in 2 (7.4%) patients each, with 1 patient each (3.7%) experiencing anastomotic leak, bowel perforation, and hemorrhage.…”