title: A phase I/II study of doxorubicin, ifosfamide, etoposide and interval methotrexate in patients with poor prognosis osteosarcoma.
abstract: BACKGROUND
  The prognosis for patients with metastatic or axial-skeletal osteosarcoma is poor. A phase I/II study was conducted of intensive chemotherapy with interval methotrexate, to assess the feasibility, response rate and toxicity in this group of patients.
  
  
  METHODS
  Thirteen patients, median age 18 (range: 8-34), with metastatic or axial-skeletal osteosarcoma were treated with ifosfamide 2.5 g/m(2), etoposide 150 mg/m(2), and doxorubicin 20 mg/m(2) on days 1-3, every 21 days, with interval methotrexate 12 g/m(2) given on day 14, for a maximum of eight cycles. Surgery to the primary was considered after four cycles for those with operable disease, or together with metastatic disease at completion of chemotherapy in those with inoperable tumours.
  
  
  RESULTS
  A total of 85 cycles were given, median 6 per patient (range: 4-8). Only 6 of the 13 patients completed all 8 cycles of chemotherapy. Forty-eight cycles (56%) required a dose reduction. The principal toxicity was myelosuppression, with a median nadir neutrophil count of 0.1 (range: 0-4.1). Grade 3 or 4 infection was seen in 41 cycles (48%). Histological response was assessable in seven patients, all of whom achieved a >or=90% necrosis. Radiological response rate, evaluable in seven patients with lung metastases, was 43%. All but one patient has had subsequent disease progression or relapse, with a median event free survival of 13 months (range: 5-53).
  
  
  CONCLUSIONS
  This regimen was associated with responses, but these were not sustained. Substantial toxicity was seen, preventing optimal delivery. More effective, less toxic regimens are needed in this group of patients.
authors.affiliation: Meyerstein Institute of Oncology, Middlesex Hospital, UCL Hospitals NHS Trust, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
authors.forename: Maria P
authors.initials: MP
authors.lastname: Michelagnoli
authors.forename: Ian
authors.initials: I
authors.lastname: Lewis
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Whelan
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002648:Child; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D004317:Doxorubicin; D007069:Ifosfamide