Received: 10 November 2017 Revised: 26 January 2018 Accepted: 25 February 2018 DOI: 10.1002/pbc.27246 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas Jonathan L. Metts 1,2,3 Adina L. Alazraki 4 Dana Clark 5 Ernest K. Amankwah 2,3 Karen J. Wasilewski-Masker 1 Bradley A. George 1 Thomas A. Olson 1 Thomas Cash 1 1 Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia 2 Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida 3 Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland 4 Department of Radiology and Imaging Sciences, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia 5 Department of Pharmacy, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia Correspondence Jonathan L. Metts, Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, 601 5th Street South St. Petersburg, FL 33701. Email: jmetts1@jhmi.edu This work was presented previously in part at the 2016 American Society of Pediatric Hematology Oncology (ASPHO) Conference in Minneapolis, MN. Funding information Grant sponsor: Celgene Corporation Abstract Background: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. Procedure: We reviewed the records of fifteen relapsed/refractory patients and one treatment- naïve patient who received gemcitabine/nab-paclitaxel at our institution. Results: Sixteen patients (median age 13.5 years, range 3–19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with non- hematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no com- plete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2–19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression- free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. Conclusions: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic tox- icities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway. KEYWORDS gemcitabine, nab-paclitaxel, refractory, relapsed, sarcoma 1 INTRODUCTION Despite scientific advances in our understanding of pediatric cancer, over 1,900 children aged 0–19 years are estimated to succumb to their disease each year. 1 Patients with relapsed and treatment-refractory sarcomas have particularly poor outcomes. In addition, many patients with metastatic disease or high-risk features at diagnosis have a Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CR, complete response; G-CSF, granulocyte colony stimulating factor; MPACT, Metastatic Pancreatic Adenocarcinoma Clinical Trial; MTD, maximum tolerated dose; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; RP2D, recommended phase 2 dose; SD, stable disease similarly dismal prognosis. 2–4 Novel therapeutic strategies are there- fore needed. Optimizing quality of life is also of great importance in this population, and this may be achieved with the administration of inno- vative therapies. 5,6 The optimal treatment for preservation of qual- ity end-of-life care should have relatively few adverse effects and not require extensive time in the hospital or clinic. The combination of the pyrimidine antimetabolite gemcitabine and agents of the taxane family (e.g. docetaxel, paclitaxel), which func- tion through microtubule disruption, have been studied extensively in several adult solid tumor malignancies, including lung cancer, breast cancer, and sarcomas. 7–10 Pediatric experience with gemcitabine/ docetaxel includes a phase II study of the combination in chil- dren and adults with relapsed/refractory bone sarcomas and several Pediatr Blood Cancer. 2018;e27246. c  2018 Wiley Periodicals, Inc. 1 of 8 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.27246