Vol.:(0123456789) 1 3 Cancer Chemotherapy and Pharmacology https://doi.org/10.1007/s00280-020-04190-1 ORIGINAL ARTICLE Exploring chemotherapy holiday and drugs re‑challenge in advanced pancreatic cancer patients Marina Macchini 1,2  · Umberto Peretti 1,2  · Giulia Orsi 1,2  · Silvia Zanon 1  · Elena Mazza 1  · Maria Maddalena Valente 1,2  · Domenico Tamburrino 2,3  · Giulio Belfori 2,3  · Gemma Rossi 2,4  · Sabrina Gloria Giulia Testoni 2,4  · Paolo Passoni 5  · Claudio Doglioni 2,6  · Stefano Cascinu 1,2  · Michele Reni 1,2 Received: 24 June 2020 / Accepted: 20 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Purpose We aimed to explore the role of drugs re-challenge at the disease progression after a chemotherapy-free interval for pancreatic adenocarcinoma (PDAC) patients. Methods We retrospectively analyzed the outcome of re-treatments at the progression in two cohorts of advanced PDAC patients who had disease control (DC) and a treatment holiday ≥ 3 months after upfront chemotherapy. Results Between 2015 and 2019, 66 advanced PDAC patients (cohort A) had DC with nab-paclitaxel-based chemotherapy (i.e. AG or PAXG = cisplatin, nab-paclitaxel, gemcitabine, capecitabine). At the time of progressive disease (PD), 34 patients were re-treated with AG (A1) and 32 were treated with other regimens (A2). The median (m) duration of chemotherapy holiday was 6.1 and 5.9 months in A1 and A2, respectively. Partial response (PR) and stable disease (SD) were found in 14 (41%) and 12 (35%) of patients in A1 and in 8 (25%) and 6 (19%) patients in A2. CA19-9 response was recorded in 23/33 evaluable patients (70%) in A1 and in 5/20 (25%) in A2. mPFS2 and mOS2, defned as the time between the second line of treatment start and the disease progression or death, were 4.8 and 12.2 months in A1 and 3.9 and 8.4 months in A2, respectively. Similarly, between 2006 and 2013, 64 patients (cohort B) had DC with upfront PEFG/PEXG/PDXG regimens (epirubicin or docetaxel, cisplatin, gemcitabine, capecitabine or 5-fuorouracil) and were re-treated at PD with either 4-drug (B1; N = 30) or other regimens (B2; N = 34), yielding a mOS2 of 10.9 and 7.2 months, respectively. Conclusion Our data endorse the strategy of resuming prior drugs after a chemotherapy holiday ≥ 3 months in advanced PDAC patients who achieved a  durable disease control after upfront treatments. Keywords Pancreatic cancer · Chemotherapy holiday · Nab-paclitaxel · Re-challenge Introduction Pancreatic adenocarcinoma (PDAC) is a highly primary chemo-resistant disease with dismal prognosis and few therapeutic options. About 80% of patients with newly diagnosed PDAC present metastatic or locally advanced disease. In this setting, FOLFIRINOX and nab-paclitaxel Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00280-020-04190-1) contains supplementary material, which is available to authorized users. * Michele Reni reni.michele@hsr.it 1 Department of Medical Oncology, IRCCS San Rafaele Scientifc Institute, Via Olgettina 60, 20132 Milan, Italy 2 Pancreas Translational and Clinical Research Center, San Rafaele Scientifc Institute, Milan, Italy 3 Pancreatic Surgery Unit, IRCCS San Rafaele Scientifc Institute, Milan, Italy 4 Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Rafaele Scientifc Institute, Milan, Italy 5 Department of Radiotherapy, IRCCS San Rafaele Scientifc Institute, Milan, Italy 6 Pathology Unit, IRCCS San Rafaele Scientifc Institute, Milan, Italy