Leo Mascarenhas1,2, Elizabeth R Lyden3, Philip P Breitfeld4,5, David O Walterhouse6, Sarah S Donaldson7, David A Rodeberg8, David M Parham9, James R Anderson3,10, William H Meyer11, Douglas S Hawkins12. 1. Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California. 2. Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California. 3. Department of Preventive and Societal Medicine, University of Nebraska, Omaha, Nebraska. 4. Duke University Medical Center, Durham, North Carolina. 5. Breitfeld Group, LLC, Chapel Hill, North Carolina. 6. Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 7. Department of Radiation Oncology, Stanford University, Stanford, California. 8. Division of Pediatric Surgery, Department of Surgery, East Carolina University, Greenville, North Carolina. 9. Department of Pathology, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California. 10. Oncology, Merck Research Laboratories, North Wales, Pennsylvania. 11. Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. 12. Department of Pediatrics, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
Abstract
BACKGROUND: The purpose of this study was to evaluate risk and response-based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. METHODS:Patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) features were randomized to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported). Those with at least a partial response to VI continued to receive 44 weeks of multi-agent chemotherapy including the assigned VI regimen. UR patients who did not have measurable disease at study entry, did not have a radiographic response after the VI window, or declined VI window therapy received 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ) at weeks 1, 4, 10, 19, and 28. Favorable-risk (FR) patients received 31 weeks of the same multi-agent chemotherapy without VI and TPZ. RESULTS:One hundred thirty-six eligible patients were enrolled. For 61 patients not responding to VI, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 17% (95% confidence interval [CI], 8%-29%) and 24% (13%-37%), respectively. For 30 UR patients not treated with VI, the 3-year FFS and OS rates were 21% (8%-37%) and 39% (20%-57%), respectively. FR patients had 3-year FFS and OS rates of 79% (47%-93%) and 84% (50%-96%), respectively. There were no unexpected toxicities. CONCLUSIONS: Patients with UR RMS at first relapse or disease progression have a poor prognosis when they are treated with this multi-agent therapy, whereas FR patients have a higher chance of being cured with second-line therapy.
RCT Entities:
BACKGROUND: The purpose of this study was to evaluate risk and response-based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. METHODS:Patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) features were randomized to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported). Those with at least a partial response to VI continued to receive 44 weeks of multi-agent chemotherapy including the assigned VI regimen. UR patients who did not have measurable disease at study entry, did not have a radiographic response after the VI window, or declined VI window therapy received 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ) at weeks 1, 4, 10, 19, and 28. Favorable-risk (FR) patients received 31 weeks of the same multi-agent chemotherapy without VI and TPZ. RESULTS: One hundred thirty-six eligible patients were enrolled. For 61 patients not responding to VI, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 17% (95% confidence interval [CI], 8%-29%) and 24% (13%-37%), respectively. For 30 UR patients not treated with VI, the 3-year FFS and OS rates were 21% (8%-37%) and 39% (20%-57%), respectively. FR patients had 3-year FFS and OS rates of 79% (47%-93%) and 84% (50%-96%), respectively. There were no unexpected toxicities. CONCLUSIONS:Patients with UR RMS at first relapse or disease progression have a poor prognosis when they are treated with this multi-agent therapy, whereas FR patients have a higher chance of being cured with second-line therapy.
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