Treatment algorithm for nonmetastatic exocrine pancreatic cancer

HRR: homologous recombination repair; CRT: chemoradiotherapy; PS: Eastern Cooperative Oncology Group performance status; ULN: upper limit of normal; FOLFIRINOX: oxaliplatin plus irinotecan with leucovorin and short-term infusional fluorouracil; FOLFOX: leucovorin plus short-term infusional fluorouracil and oxaliplatin; nabpaciltaxel: nanoparticle albumin-bound paclitaxel; RT: radiation therapy; BRCA: breast cancer susceptibility gene; PALB2: partner and localizer of BRCA2.

* UpToDate authors consider either approach to be reasonable; practice varies among experts.

¶ Genes associated with HRR deficiency include BRCA1/2, PALB2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1.

Δ Irinotecan could be added to later cycles if mutations are discovered in BRCA or PALB2 and the patient has tolerated FOLFOX adequately.

◊ Many clinicians would not administer gemcitabine for a total bilirubin above 2.5 ng/mL.

§ If poor performance status is due to recent infection (eg, cholangitis) and the patient is recovering well after intervention, dose-adjusted combination chemotherapy is preferred over single-agent gemcitabine. If performance status is poor due to locally advanced disease causing disabling pain and/or gastric outlet obstruction, aggressive symptom management should be undertaken prior to initiating chemotherapy.

¥ At some institutions, patients with a very good response to neoadjuvant chemotherapy would be taken directly to surgical exploration. However, some clinicians would offer fluorouracil-based CRT (or stereotactic body RT, refer to UpToDate text) or additional chemotherapy alone if there is concern that a microscopically complete (R0) resection won't be possible. However, it is unknown whether any form of RT contributes to the R0 resection rate after chemotherapy (especially for combination regimens such as FOLFIRINOX). Furthermore, imaging assessment of resectability may be unreliable after multiagent chemotherapy. If additional therapy is given, reevaluate for surgical exploration 6 weeks post-treatment.