Induction chemotherapy with FOLFIRINOX in pancreatic cancer and then? Experience with a novel scheme of maintenance, treatment pause and re-induction

Introduction: Chemotherapy regimens for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX (5-fluoruracil (5FU/LV), Oxaliplatin, Irinotecan and Leucovorin) which confer a significant survival benefit compared to gemcitabine-based monotherapy. Increased toxicity, mainly sensory peripheral neuropathy, limits its use and the number of applied chemotherapy cycles. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance, treatment pause and re-induction therapy in locally advanced or metastatic PDAC to alleviate such toxicities and increase the number of applied cycles. In this retrospective study we report our experience with this scheme.

Methods: We retrospectively identified all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using the induction and maintenance scheme from 2011 until February 2016. Response to therapy and toxicity of the treatment were assessed. Progression free survival was assessed until progression during maintenance or treatment pause (PFS1) and until progression during re-induction therapy (PFS2).

Results: 13 patients met the inclusion criteria. The median number of cycles of induction therapy including all three active substances or only 5FU/LV combined with Oxaliplatin was 6 (range 5 – 13). All patients had stable disease or partial response and received maintenance therapy consisting of 5FU/LV with a median cycle number of 6 (2 – 21). Four patients had a treatment pause after maintenance therapy of median 24.4 weeks (8 – 42.1). Re-induction due to progressive disease during treatment pause or maintenance therapy was applied in nine patients using all three active substances or only 5FU/LV combined with Oxaliplatin, with a median of 4 (1 – 7) cycles of re-induction therapy. The median PFS1 was 10.8 months. The median PFS2 was 14.1 months.

Conclusion: The use of induction treatment with FOLFIRINOX, followed by maintenance therapy with the option of treatment pause and re-induction in case of progressive disease is feasible in the palliative treatment of PDAC patients and might lead to a prolonged progression free survival with less toxicity.