Safety and Cost-effectiveness of Outpatient Administration of High-dose Chemotherapy in Children With Ewing Sarcoma Alya Elshahoubi, MD,* Anwar Alnassan, MD,*† and Iyad Sultan, MD*† Background: Children with Ewing sarcoma (ES) are subjected to an interval-compressed regimen with cycles of chemotherapy given every 2 weeks, which is nowadays considered to be the standard of care for individuals with such a case. We developed institutional clinical practice guidelines (CPG) applying outpatient admin- istration in regard to this regimen. This study intends to evaluate our institutional experience with this regimen. Methods: We conducted a retrospective review of patients with ES who were treated using interval-compressed protocol of 14 cycles consisting of alternating cyclophosphamide, doxorubicin, vincris- tine (VDC) and ifosfamide, etoposide (IE) with a maximum dose of doxorubicin of 375 mg/m 2 . Cycles were subsequently followed by G-CSF administration until count recovery was recorded. Patients treated using our guidelines from June 2013 to June 2015 were eligible for these guidelines. Patients younger than 3 years at the time of diagnosis were not eligible for outpatient administration of chemotherapy. Results: In total 12 patients with localized ES or lung-only meta- stasis were eligible. By the time of analysis, 153 cycles were administered to these patients. Eight cycles for 6 patients were administered on an inpatient basis while the rest (N = 145) were administered in the outpatient chemotherapy unit. The median number of cycles per patient were 14 (with a range of 5 to 14). Ninety cycles (59%) were administered on time per CPG. The median interval between these cycles were 16 days (range, 12 to 36 days). The median interval between induction and consolidation cycles were 14 and 17 days, respectively. Neutropenia was reported at the time of each next cycle for 12 cycles. Transient gross hema- turia was reported in 1 patient only. In addition, a cost saving of 21% (approximately US$ 4500) were achieved per patient. Conclusions: Our study showed that the outpatient administration of interval-compressed regimen is safe and associated with accept- able adherence to this regimen. Key Words: Ewing sarcoma, interval-compression, outpatient, ifosfamide, chemotherapy, pediatric (J Pediatr Hematol Oncol 2019;41:e152–e154) E wing Sarcoma (ES) is the second most common primary bone malignancy in children and adolescents. 1 Chemo and radiosensitivity has led to marked improvement in patient outcome. The addition of ifosfamide and etoposide (IE) to a regimen of vincristine, doxorubicin and cyclo- phosphamide (VDC) has led to improved outcomes of patients with localized ES. 2 Intensification with increased dosing of chemotherapy did not lead to consistent improvement of outcomes in patients with ES. 3,4 Recently, the Children’s Oncology Group (COG) published the results of NCT00006734. In this landmark trial, 587 patients with nonmetastatic ES were randomized to receive a regular schedule of VDC alternating with IE compared to a regimen that utilized interval-compression with a 2-week interval between cycles. With similar toxicity profile, patients who received the arm utilizing interval compression had improved outcomes, with 5-year event free survival of 73% compared with 65% in the standard arm (P = 0.048). 5 This has made interval compression the new gold-standard in localized ES treatment in children and adolescents. Although this regimen is typically administered on an inpatient basis, we have developed an institutional Clinical Practice Guidelines (CPG) using previously published pro- tocols where ifosfamide was administered safely on an outpatient basis. 6 Administering the regimen in this way can save precious inpatient beds and possibly reduces the cost of treatment. In this study we evaluated our experience in using this CPG over a period of 2 years. METHODS We conducted a retrospective review of all patients with ES who were treated using interval-compressed protocol from June 2013 to June 2015. We used the Pedia- tric Oncology Network Database (POND) adopted by our department since June 2006 to identify patients with ES treated during the studied period. We excluded patients younger than 3 years at the time of diagnosis, those with multiple sites of metastasis, and patients who relapsed from this analysis. According to our institutional CPG, patients with ES who presented with localized disease or one site of meta- stasis are treated using 14 cycles of alternating cyclo- phosphamide, doxorubicin, vincristine (VDC), and ifosfa- mide etoposide (IE) with a maximum dose of doxorubicin of 375 mg/m 2 . GCSF was administered 24 hours following each cycle and until ANC was above 1000/μL. If ANC remains below 750/μL at time of administration then the next cycle of GCSF is continued until ANC is above 1000, where it is subsequently stopped, upon which ANC is rechecked after 48 hours before administering the next cycle. Outpatient ifosfamide infusion was adopted from a pre- viously published report. 6 Urine analysis was sent and recorded at the following milestones: before starting che- motherapy on a daily basis, one day after administering the last dose of ifosfamide and if a patient developed any Received for publication March 18, 2018; accepted November 28, 2018. From the *Department of Pediatrics, King Hussein Cancer Center; and †Department of Pediatrics, the University of Jordan, Amman, Jordan. The authors declare no conflict of interest. Reprints: Iyad Sultan, MD, King Hussein Cancer Centre, Queen Rania Street, PO Box 1269 Al-Jubeiha, Amman 11941, Jordan (e-mail: isultan@khcc.jo). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE e152 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 41, Number 3, April 2019 Copyright r 2019 Wolters Kluwer Health, Inc. All rights reserved.