Induction gemcitabine and oxaliplatin therapy followed by a twice‐weekly infusion of gemcitabine and concurrent external‐beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer

Abstract

BACKGROUND: Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. METHODS: Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2). Patients without disease progression then received gemcitabine twice weekly (50 mg/m2 daily) concurrent with radiotherapy (50.4 grays) and were re‐evaluated for resectability. RESULTS: Thirty‐nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow‐up of 13 months, the median progression‐free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). CONCLUSIONS: The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. Cancer 2013. © 2012 American Cancer Society.

The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

“…Neoadjuvant therapy with the intent of sterilizing the margin could be considered in patients with vascular involvement, with particular attention to restaging to tailor surgical recommendations. Several studies suggest that neoadjuvant chemoradiation may enhance margin-negative resectability rates and improve local control [37,[56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Unfortunately, many of the studies are confounded by inclusion of patients with locally advanced unresectable tumors and lack of strict definition of borderline resectable disease.…”

“…Data from prospective trials containing patients with borderline resectable disease demonstrate that the surgical resection rate ranges from 24 to 64%, and the R0 resection rate ranges from 87 to 100% [56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Although most of these studies are small, neoadjuvant chemoradiation appears to be associated with good potential for downstaging and R0 resection in this population, which may be in part due to careful patient selection with adequate staging studies, and strict adherence to the definition of borderline resectable.…”

Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer

“…A single institution reported 22 LAPC patients who were treated with SBRT (45 Gy/3 fractions over 5-10 days) [47]. Acute toxicity was significant.…”

“…Two of the patients experienced grade 3 toxicity [21]. In contrast, 45-Gy RT was administered over 5-10 days in 22 LAPC patients, whose mOS was 5.7 months; only 1 patient was alive at 1 year of follow-up [47]. Table 2 summarizes the results of recently conducted trials in LAPC.…”

Advances in Chemotherapy for Pancreatic Cancer

“…After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % and the 1-year overall survival was 100 %. Table 2 shows results of some key studies of neoadjuvant strategy in patients with pancreatic cancer [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. The pragmatic trial from the Intergroup would throw light on how to manage these patients optimally-all patients with borderline resectable pancreatic cancer receive FOLFIRINOX for 4 cycles followed by chemoradiotherapy with capecitabine and if stable or responding, patients are taken for surgery 6-8 weeks post-completion of radiotherapy.…”