Farzana Pashankar1, A Lindsay Frazier2, Mark Krailo3, Caihong Xia4, Alberto S Pappo5, Marcio Malogolowkin6, Thomas A Olson7, Carlos Rodriguez-Galindo5,8. 1. Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut. 2. Department of Pediatrics, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts. 3. Department of Preventive Medicine, University of Southern California, Los Angeles, California. 4. Statistics and Data Center, Children's Oncology Group, Monrovia, California. 5. Department of Pediatric Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 6. Department of Pediatrics, UC Davis Children's Hospital, Sacramento, California. 7. Department of Pediatrics, Aflac Cancer Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia. 8. Departments of Global Pediatric Medicine and Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
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/m2 /day Day 1, ifosfamide 1,800 mg/m2 /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.
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/m2 /day Day 1, ifosfamide 1,800 mg/m2 /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.
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