Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer

Abstract

Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.

Neoadjuvant and Adjuvant Chemotherapy for Pancreatic Adenocarcinoma: Literature Review and Our Experience of NAC-GS

“…In addition, they also showed that the resection rate and R0 resection rate were similar in patients who did and did not receive NAC-GS, although the rate of administration of AC was increased in the former group. Our results were in line with those of a previous meta-analysis in some respects [8] but different from those of the Prep-02/JSAP05 study, which showed a survival benefit of NAC-GS [25]. A recent meta-analysis also suggested that NAT is associated with a lower risk of development of lymph node metastasis, an improved R0 resection rate, and improved recurrence-free and overall survivals in patients with resectable disease [11].…”

“…The five-year overall survival rates were 20.5% in the test arm and 6.5% in the control arm [ 25 ]. However, the results of meta-analyses have been conflicting [ 8 , 11 ]. More recently, the effectiveness of modified FOLFIRINOX in a neoadjuvant setting has been examined [ 26 ].…”

“…In addition, dose reduction during AT is frequently needed in postoperative patients, resulting in a weakened efficacy of the treatment. From this standpoint, neoadjuvant therapies (NATs) might be more reasonable, because NATs can be applied to more patients scheduled for curative resections, with more reliable treatment intensity [ 8 ]. On the other hand, complications associated with NATs may also preclude curative resection in potentially resectable patients, and, at present, there are no measures to predict the benefits/disadvantages of NATs.…”

“…On the other hand, complications associated with NATs may also preclude curative resection in potentially resectable patients, and, at present, there are no measures to predict the benefits/disadvantages of NATs. A number of excellent reviews and meta-analyses have traced the development of NAT/AT for PDAC and discussed its significance [ 8 , 9 , 10 , 11 ]. Herein, we discuss some unresolved issues associated with NAT/AT for PDAC.…”

Increased Levels of miR-15b-5p and miR-20b-5p in Pancreatic Ductal Adenocarcinoma with Hepatic Metastases

“…According to a growing body of research, neoadjuvant chemotherapy is increasingly being used as a therapeutic option for patients with pancreatic cancer who may otherwise be candidates for surgery [ 7 ]. Conroy et al demonstrated that, despite having a greater prevalence of severe side effects, adjuvant treatment with a modified FOLFIRINOX regimen (leucovorin, 5-fluorouracil, irinotecan and oxaliplatin) resulted in considerably longer survival times than gemcitabine among patients with resected pancreatic cancer [ 8 ].…”