Adjuvant chemotherapy is the standard treatment for patients with resectable
pancreatic ductal carcinoma. Perioperative
chemotherapy has been given in less than 50% of patients with potentially resectable
pancreatic cancer in Japan. A modified combination regimen of
5-fluorouracil,
leucovorin,
irinotecan, and
oxaliplatin (mFOLFIRINOX;
oxaliplatin 85 mg/m2,
leucovorin 400 mg/m2,
irinotecan 150 mg/m2 on day 1, and
5-fluorouracil 2,400 mg/m2 over 46 hours every 14 days for 12 cycles) is now preferred worldwide because it mitigates concerns regarding toxicity and tolerance. Adjuvant chemotherapeutic regimens employ S-1 in East Asia, whereas other areas use
FOLFIRINOX,
capecitabine plus
gemcitabine, or
gemcitabine monotherapy.
Adjuvant chemoradiotherapy is not recommended because randomized controlled trials and meta-analyses revealed no survival benefit compared with
chemotherapy. Preoperative
chemotherapy with S-1 and
gemcitabine combination chemotherapy for patients with resectable/borderline resectable
pancreatic cancer significantly increased survival compared to upfront surgery in a recent clinical trial. Perioperative outcomes, including R0 resection rate and post-operative morbidity, were not significantly different between groups. When compared to upfront surgery, neoadjuvant S-1 and
gemcitabine treatment significantly reduced the number of pathological nodal
metastases in patients who underwent resection. Japanese guidelines therefore recommend
neoadjuvant chemotherapy for patients with resectable
pancreatic cancer. Preoperative
chemotherapy can increase R0 cases by down-staging with higher relative dose intensity of
chemotherapy. In contrast, patients who do not respond to
chemotherapy may miss resection opportunities and would therefore be at a disadvantage. Therefore, it is critical for both patients and doctors that predictive markers for the response to
chemotherapy are identified.