Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study

• Type of Material: Conference Paper
• Authors: Farzana Pashankar, Yale University; A. Lindsay Frazier, Dana Farber/ Boston Children's Cancer and Blood Disorders Center; Mark Krailo, University of Southern California; Caihong Xia, Children's Oncology Group; Albert S. Pappo, St Jude Children's Research Hospital; Marcio Malogolowkin, UC Davis Children's Hospital; Thomas Olson, Emory University; Carlos Rodriguez-Galindo, St Jude Children's Research Hospital
• Language: English
• Date: 2018-08-01
• Publisher: Emory University Libraries
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/pbc.27111
• Title of Journal or Parent Work: Pediatric Blood Cancer
• Volume: 65
• Issue: 8
• Start Page: e27111
• End Page: e27111
• Grant/Funding Information: Research reported in this paper was supported by the Children’s Oncology Group, the National Cancer Institute of the National Institutes of Health under award number NCTN Operations Center Grant U10CA180886, NCTN Statistics & Data Center Grant U10CA180899, St. Baldrick’s Foundation
• Keywords: Science & Technology; Life Sciences & Biomedicine; malignant germ cell tumor; Hematology; Pediatrics; PHASE-II; pediatric; CISPLATIN; Oncology; ETOPOSIDE; relapse; PLUS IFOSFAMIDE; HIGH-DOSE CHEMOTHERAPY; CANCER; chemotherapy; 2ND-LINE THERAPY; SALVAGE THERAPY; TRIAL; TRANSPLANTATION
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Background: Paclitaxel, ifosfamide, cisplatin (TIP) is commonly used as salvage for malignant germ cell tumors (MGCT) in adults; however, additional administration of cisplatin at a young age could cause significant short- and long-term toxicities in a group of patients with high expected salvage. Because carboplatin has been shown to be effective in pediatric MGCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. Methods: The Children's Oncology Group conducted a phase II trial between November 2007 and June 2011 evaluating “TIC” (paclitaxel 135 mg/m 2 /day Day 1, ifosfamide 1,800 mg/m 2 /dose Days 1–5 and carboplatin with AUC 6.5 Day 1) in children < 21 years with relapsed MGCT. The endpoint of the trial was response after two cycles, incorporating RECIST response and marker decline. Results: Twenty patients (12 male, median age 13.5 years) were enrolled. Seventeen patients had tumor markers ≥10 times above normal. After two cycles, by RECIST criteria, 8 patients achieved a partial response (response rate 40%), 10 had stable disease, and 2 had progressive disease. A ≥ 1 log reduction was achieved in 10/17 patients (58.8%) with elevated markers. By study defined criteria, combining response by RECIST and marker decline, the response rate was 44%. Conclusion: TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high-dose chemotherapy with stem cell remain the standard therapy.