title: Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed ewing sarcoma at a single institution.
abstract: The combination of cyclophosphamide and topotecan (cyclo/topo) has shown objective responses in relapsed Ewing sarcoma, but the response duration is not well documented. We reviewed characteristics and outcome of 14 patients with Ewing sarcoma, treated uniformly at a single institution and offered cyclo/topo at first relapse. Six patients (43%) had relapse at distant sites. All patients received first-line salvage therapy with cyclophosphamide 250 mg/m and topotecan 0.75 mg/m, daily for 5 days repeated every 21 days. The median number of cycles was 4 (range 1 to 10). All toxicities were manageable, the most common being transient cytopenias. There were also 4 episodes of febrile neutropenia, and 3 episodes of gross hematuria. Response was assessable in 13 patients and showed progressive disease in 6 (46%), stable disease in 4 (31%), and partial response in 3 (23%). Nine patients had local control, consisting of radical surgery in 2, radiation in 3, and a combination in 4 patients. Response, when it occurred, was maintained for a median of 8 months (range, 4 to 28 mo). Four patients (29%) are alive at 3, 7, 9, and 110 months after relapse; 1 is receiving cyclo/topo, 1 is on third-line therapy, and 2 are in second and fourth remission. The low toxicity of this combination, and the lack of sustained responses, warrant its investigation in combination with targeted or novel therapeutic agents in relapsed disease.
authors.affiliation: Department of Pediatric and Adolescent Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Rawad
authors.initials: R
authors.lastname: Farhat
authors.forename: Roy
authors.initials: R
authors.lastname: Raad
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Khoury
authors.forename: Julien
authors.initials: J
authors.lastname: Feghaly
authors.forename: Toufic
authors.initials: T
authors.lastname: Eid
authors.forename: Samar
authors.initials: S
authors.lastname: Muwakkit
authors.forename: Miguel
authors.initials: M
authors.lastname: Abboud
authors.forename: Hassan
authors.initials: H
authors.lastname: El-Solh
authors.forename: Raya
authors.initials: R
authors.lastname: Saab
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019772:Topotecan; D003520:Cyclophosphamide