Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence

Abstract

At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.

Neoadjuvant Therapy for Neuroendocrine Neoplasms: Recent Progresses and Future Approaches

“…Since several patients are diagnosed with metastatic disease, curative surgery is usually not an option (1), palliative surgical intervention possibly being effective in controlling clinical symptoms and improving patient's quality of life (2)(3)(4). Neoadjuvant therapy, with the aim of reducing tumor size and disease burden, can potentially change the clinical scenario making it suitable for curative surgery as already demonstrated in other cancer types (5)(6)(7)(8). While it is conceivable that neoadjuvant chemo-and radiotherapy might be effective in NENs (9), reliable evidence is still lacking in this field and study results are difficult to compare due the heterogeneity of both neoadjuvant therapies used, and series studied.…”

Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review

“…The remaining cases are considered to have unresectable locally advanced, borderline resectable, or metastatic disease ( 14 ). In this setting, the introduction of neoadjuvant chemotherapy or radiochemotherapy seems to offer potential advantages, such as the increase of the R0 resection rates in borderline resectable tumors or the conversion of locally advanced tumors to resectable ones ( 14 ). Examples of neoadjuvant chemotherapy that have been successfully used in the setting of pancreatic cancer includes FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, oxaliplatin) or gemcitabine-based chemotherapy or capecitabine-based chemotherapy ( 14 ).…”

“…In this setting, the introduction of neoadjuvant chemotherapy or radiochemotherapy seems to offer potential advantages, such as the increase of the R0 resection rates in borderline resectable tumors or the conversion of locally advanced tumors to resectable ones ( 14 ). Examples of neoadjuvant chemotherapy that have been successfully used in the setting of pancreatic cancer includes FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, oxaliplatin) or gemcitabine-based chemotherapy or capecitabine-based chemotherapy ( 14 ). The dissemination pattern of pancreatic adenocarcinoma is through its microenvironment, which plays a crucial role to local invasion of anatomical structures, lymphatics and blood vessels, leading to early metastases ( 15 ).…”

“…Complete surgical resection at an early stage is the only treatment option with a curative potential (8,9); however, lack of early symptomatology makes this effort feasible for <20% of newly diagnosed patients (10)(11)(12)(13). The remaining cases are considered to have unresectable locally advanced, borderline resectable, or metastatic disease (14). In this setting, the introduction of neoadjuvant chemotherapy or radiochemotherapy seems to offer potential advantages, such as the increase of the R0 resection rates in borderline resectable tumors or the conversion of locally advanced tumors to resectable ones (14).…”

Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

“…These strategies have not shown to improve patient survival significantly. Neo-adjuvant therapy is given to patients with marginally resectable or early-stage tumor, in which case chemotherapy is provided before surgery [ 19 ]. The role of radiation in treatment is still not clear, with some data suggesting radiation in neo-adjuvant setting to be helpful [ 20 ].…”