Expert Review of Gastroenterology & Hepatology

ISSN: 1747-4124 (Print) 1747-4132 (Online) Journal homepage: http://www.tandfonline.com/loi/ierh20

Novel directions in neoadjuvant therapy for pancreas adenocarcinoma Andrew Yang & Eileen M O’Reilly To cite this article: Andrew Yang & Eileen M O’Reilly (2015) Novel directions in neoadjuvant therapy for pancreas adenocarcinoma, Expert Review of Gastroenterology & Hepatology, 9:5, 585-601 To link to this article: http://dx.doi.org/10.1586/17474124.2015.1012496

Published online: 16 Feb 2015.

Submit your article to this journal

Article views: 81

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierh20 Download by: [University of California, San Diego]

Date: 11 November 2015, At: 03:46

Review

Novel directions in neoadjuvant therapy for pancreas adenocarcinoma Downloaded by [University of California, San Diego] at 03:46 11 November 2015

Expert Rev. Gastroenterol. Hepatol. 9(5), 585–601 (2015)

Andrew Yang and Eileen M O’Reilly* Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th street, Office 1021, New York, NY 10065, USA *Author for correspondence: Tel.: +1 646 888 4182 Fax: +1 646 888 4542 [email protected]

Surgical resection of pancreatic carcinoma has long represented the only viable option for a potential cure of pancreas cancer. The use of adjuvant chemotherapy post-resection has been established in treating micro metastases and prolonging disease-free survival. However, studies of neoadjuvant therapy have not come to any definitive conclusion regarding the overall efficacy of such treatment, despite the theoretical benefits. In this review, we examine the historical precedent as well as the current state of affairs regarding neoadjuvant therapy in resectable and borderline resectable pancreatic adenocarcinoma. In addition, we review the definitions for resectable and borderline resectable disease and highlight key areas of clinical investigation in the field and summarize the major ongoing neoadjuvant studies focused on resectable pancreatic adenocarcinoma. KEYWORDS: adjuvant . borderline respectable . FOLFIRINOX . gemcitabine . neoadjuvant . pancreatic cancer

The rationale for neoadjuvant therapy

An estimated 45,000 cases of pancreatic cancer are diagnosed per year, making it the ninth to tenth most prevalent cancer in the USA [1]. Despite the lower incidence compared to other solid tumor malignancies such as lung, colon, prostate and breast cancer, it is the fourth most lethal, owing to the fact that the majority of patients present with late-stage disease and succumb within a short period of time to the disease. Despite recent advances in systemic therapy, less than 7% of those diagnosed with this disease will be alive in 5 years [2]. Although surgical resection remains the sole modality for a potential cure, post-surgical disease recurrence is nearly inevitable, with most recurrences occurring within 6–24 months of initial resection, indicating the aggressive biology of the disease [3]. The role of neoadjuvant therapy in other solid organ malignancies such as breast and colon cancer has been more widely integrated [1,2], and while neoadjuvant therapy is not accepted as standard of care for patients with resectable pancreatic adenocarcinoma, some of the theoretical advantages remain the same – improving resection margin negative (R0) resection rates and treating distant micro-

informahealthcare.com

10.1586/17474124.2015.1012496

metastases not seen with initial radiographic staging, along with in vivo tumor response assessment [4,5]. Neoadjuvant therapy would also, in theory, increase exposure to systemic therapy prior to surgery to all patients and offset the time off treatment during the postoperative recovery period where effective therapy delivery can be delayed due to postoperative morbidity [6]. Despite these theoretical advantages, neoadjuvant therapy is not widely accepted as a standard of care, although it is an emerging treatment paradigm in borderline resectable pancreatic adenocarcinoma, and current National Comprehensive Cancer Network (NCCN) guidelines recommend neoadjuvant therapy for borderline resectable disease [5,7]. However, the questions of when to administer therapy, and which is the optimal therapy and for what duration to give in pancreatic adenocarcinoma, remain unanswered. Trials exploring the answers to these questions have been hampered by the incorporation of patients with various disease settings, including often resectable, borderline resectable and locally advanced patients in small single-institution trials [8,9]. In this review article, we evaluate the need for clear definitions of borderline resectability, review historical and current

 2015 Informa UK Ltd

ISSN 1747-4124

585

Review

Yang & O’Reilly

Downloaded by [University of California, San Diego] at 03:46 11 November 2015

Table 1. Definitions of borderline resectable disease. AHPBA/SSAT/ SSO [14]

MD Anderson

Superior mesenteric artery

Abutment

Abutment less than or equal to 180 degrees

Abutment

Novel directions in neoadjuvant therapy for pancreas adenocarcinoma.

Surgical resection of pancreatic carcinoma has long represented the only viable option for a potential cure of pancreas cancer. The use of adjuvant ch...
579KB Sizes 1 Downloads 5 Views