title: Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group.
abstract: BACKGROUND
  The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated.
  
  
  METHODS
  Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS).
  
  
  RESULTS
  Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%).
  
  
  CONCLUSIONS
  The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.
authors.affiliation: The Saban Research Institute, Children's Hospital Los Angeles, California.|Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
authors.affiliation: Department of Pediatrics- Hematology and Oncology, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington.
authors.forename: Judy L
authors.initials: JL
authors.lastname: Felgenhauer
authors.affiliation: Department of Pediratics- Hematology and Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Mason C
authors.initials: MC
authors.lastname: Bond
authors.affiliation: Statistics and Data Center, Children's Oncology Group, Monrovia, California.
authors.forename: Doojduen
authors.initials: D
authors.lastname: Villaluna
authors.affiliation: Department of Surgery- Orthopaedics, City of Hope National Medical Center, Duarte, California.
authors.forename: Joseph Dominic
authors.initials: JD
authors.lastname: Femino
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Laack
authors.affiliation: Department of Pathology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Sarangarajan
authors.initials: S
authors.lastname: Ranganathan
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Meyer
authors.affiliation: Department of Pediatrics- Oncology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Womer
authors.affiliation: Department of Pediatrics- Hematology and Oncology, The Children's Hospital at Montefiore, The Albert Einstein College of Medicine of Yeshiva University, Bronx, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.affiliation: Department of Pediatrics- Hematology and Oncology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krailo
authors.affiliation: Lucille Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Neyssa
authors.initials: N
authors.lastname: Marina
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D010865:Pilot Projects; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy; D019772:Topotecan / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D014750:Vincristine; D005047:Etoposide; D019772:Topotecan; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide
keywords: Ewing sarcoma; PNET; cyclophosphamide; dose dense; interval compression; topotecan