1. Introduction Discussion CT abdomen 3/3/06 lightheadedness and watery diarrhea. TSH was again less than 0.01, and ACTH less than 5. AST and ALT were 240 and 150, respectively, elevated from 71 and Methods 14 DAY CONTINUOUS INFUSION HIGH-DOSE IFOSFAMIDE IN ADOLESCENT AND ADULT SARCOMA PATIENTS Andrew Hendifar, Shelly Chawla, Sandeep Nagre, Vicky Chua, Lita Fernandez, Bartosz Chmielowski, James Hu, and Sant Chawla Sarcoma Oncology Center, Santa Monica, CA University of Southern California, Division of Oncology, Los Angeles, CA UCLA Sarcoma Program, Medical Oncology, Los Angeles, CA Continuous infusion high dose ifosfamide has shown efficacy and tolerability in pediatric patients with sarcoma. In the adult population, retrospective series demonstrate promise in patients and even in patients previously treated with ifosfamide. We studied this regimen in adult and adolescent patients with bone and soft tissue sarcomas. Ifosfamide 1 g/m2/day with equivalent doses of mesna was given continuously by ambulatory infusion pump over 14 days. This regimen was prescribed every 28 days with growth factor support. 27 consecutive patients with measurable disease were enrolled from 08/25/10 until 08/15/11. 24 of the 27 patients studied were assessable for response (Recist 1.1). Our cohort included the following histologies: leiomyosarcoma (24%), liposarcoma (12%), osteosarcoma (12%) and vascular tumors (12%). Median age was 45 years with a range between 12 and 66 years of age. TABLE 1. Patient Characteristics Patients27 Median Age45, (12-66) Gender Male Female 15 (56%) 12 (54%) Histologic Subtype Leiomyosarcoma Liposarcoma Vascular tumors Osteosarcoma Others 8 (30%) 3 (11%) 10 (37%) Previous Lines of Chemotherapy One line Two lines Three lines Four or more lines Previous ifosfamide 5 (19%) 8 (30%) 5 (19%) 9 (33%) 8 (30%) Results Response to CIV Ifosfamide by Histology Best Response Leiomyo- sarcoma Vascular Tumors OtherTotal Complete Response -- 11 (4%) Partial Response 33410 (42%) Stable Disease 1--67 (29%) Progressive Disease 3--36 (25%) All except one patient (alveolar soft part sarcoma) were pretreated with up to 7 chemotherapeutic regimens (median, 3 regimens). There were 11 responses (CR+PR 11/24, 46%) to date with a disease control rate (CR+PR+SD) of 75%. The regimen was well tolerated. No renal or bladder toxicity was noted. There were 2 occurrences of grade 3 neurotoxicity and 1 grade 3 hepatotoxicity in a single patient with diffuse liver metastases and low baseline albumin. There were 2 incidences of neutropenic fever in over 70 cycles of therapy. Continuous infusion high dose ifosfamide at 1gm/m2/day over 14 days is highly active and well tolerated in a heavily pretreated cohort. We have confirmed reports of activity in patients previously treated with ifosfamide. A comparative effectiveness study is warranted to compare cost/benefit and patient preference between 14 day and 7 day regimens. 46 yo woman with recurrent uterine LMS and metastases to liver and mesentery. Progressed through Adriamycin, Dacarbazine, Gemcitabine, Docetaxel, and Trabectedin. Received 11 cycles and plan for liver and mesenteric resection. 11/201010/2011 26 yo woman with locally recurrent synovial cell cancer after neoadjuvant and adjuvant ifosfamide and adriamycin. After 8 cycles of Ifosfamide was sent for re- resection. Pathology demonstrated 90% necrosis 08/2010 05/2011

2. TABLE 1. Patient Characteristics Patients26 Median Age45, (12-66) Gender Male Female 15 (58%) 11 (42%) Histologic Subtype Leiomyosarcoma Liposarcoma Vascular umors Osteosarcoma Others 7 (27%) 3 (12%) 10 (38%) Previous Lines of Chemotherapy One line Two lines Three lines Four or more lines 4 (15%) 8(30%) 5 (19%) 9 (35%)

3. Response to CIV Ifosfamide by Histology Best Response LeiomyosarcomaOsteosarcomaLiposarcom a Vascular TumorsOtherTotal Complete Response -- 14% Partial Response 3113242% Stable Disease 121--329% Progressive Disease 3--1 225%