Neoadjuvant Chemotherapy for Localized Pancreatic Cancer: Too Little or Too Long?

Excerpt

For a “systemic” disease such as pancreatic cancer, neoadjuvant chemotherapy is a logical approach that thus far has been limited largely by a lack of effective systemic agents. For example, when considering treatment sequencing for patients with resectable disease, the concept of offering a treatment with an objective response rate of less than 10 % (as for gemcitabine alone) has been unacceptable to most clinicians. (Chemo)radiation has therefore been the backbone of most neoadjuvant approaches, with the goal of improving local/regional disease control (preventing local recurrence) and avoiding operation in those with progressive disease found on post-treatment, preoperative restaging. A few neoadjuvant studies to date have included relatively short courses of chemotherapy—without any obvious improvement in outcomes compared with chemoradiation alone.1 To further complicate treatment sequencing controversy, surgeons have cautioned that many patients (and referring physicians) want their tumors resected tomorrow and can find a surgeon who will accommodate them. Concerns about increased perioperative morbidity (following neoadjuvant therapy) still exist but have been allayed by several studies, including a recent NSQIP analysis.2 Importantly, an “effective” neoadjuvant chemotherapy regimen could theoretically improve long-term outcomes by successfully treating (possibly even eradicating) micrometastatic disease in the setting of an immune-competent host who is not attempting to recover from a large operation. The duration of neoadjuvant chemotherapy is a critical variable. If the right drug is selected for the right patient, treatment will need to be long enough to effectively treat micrometastatic disease. If the wrong drug(s) is selected (we only learn this in retrospect when restaging is performed), treatment should be short enough to avoid losing a window of resectability due to local disease progression. This is an important consideration in patients with resectable and borderline resectable disease (in contrast to those patients with locally advanced pancreatic cancer—thus the importance of accurate pretreatment staging). At present, there is little evidence to support any specific neoadjuvant treatment duration, although opinions exist that are based largely on personal experience, extrapolation from other solid tumor sites, and translational laboratory science. …