title: Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial.
abstract: OBJECTIVE
  Relapse remains a significant problem in patients with metastatic osteosarcoma. The response to carboplatin of patients with newly diagnosed metastatic or unresectable osteosarcoma was assessed in an upfront phase II window, which was followed-up by surgery and intensive multiagent chemotherapy.
  
  
  METHODS
  Thirty-seven patients, ages 3 to 23 years with histologically confirmed diagnoses of osteosarcoma, were treated between January 1992 and November 1994 with carboplatin 1,000 mg/m2 per dose administered as a 48-hour continuous infusion. Two courses were administered in 3-week intervals, depending on marrow recovery. After radiographic reevaluation, patients underwent surgical removal of tumor (if feasible) and then 40 weeks of chemotherapy with high-dose methotrexate, ifosfamide, doxorubicin, and cisplatin.
  
  
  RESULTS
  One of the 37 evaluable patients demonstrated a partial response to carboplatin; there were no complete responses. Patients were additionally analyzed by the response of pulmonary metastases to therapy and the extent of tumor necrosis of the primary lesion. By these criteria, 8 of 37 (22%) of patients showed a response at one or more sites, whereas 20 of 37 (54%) had unequivocal disease progression. Severe myelosuppression was the major toxicity. The projected 3-year event-free and overall survival rates were 23.9% and 31.9%, respectively. Only 1 of 17 patients with unresectable disease or distant bone metastases remains alive, in contrast to 6 of 17 patients with the lung as their only metastatic site and two of three patients with resected regional bone metastases.
  
  
  CONCLUSIONS
  Continuous-infusion carboplatin demonstrated limited activity as an upfront agent in patients with metastatic osteosarcoma at diagnosis, even at doses that result in severe and prolonged myelosuppression. Patients with isolated pulmonary metastases or resectable bone metastases have a longer median survival time and greater chance of long-term survival than do patients with unresectable bone disease, for whom the prognosis remains dismal.
authors.affiliation: Rhode Island Hospital and Brown University School of Medicine, Providence 02903, USA. wferguson@lifespan.org
authors.forename: W S
authors.initials: WS
authors.lastname: Ferguson
authors.forename: M B
authors.initials: MB
authors.lastname: Harris
authors.forename: A M
authors.initials: AM
authors.lastname: Goorin
authors.forename: M C
authors.initials: MC
authors.lastname: Gebhardt
authors.forename: M P
authors.initials: MP
authors.lastname: Link
authors.forename: S J
authors.initials: SJ
authors.lastname: Shochat
authors.forename: G P
authors.initials: GP
authors.lastname: Siegal
authors.forename: M
authors.initials: M
authors.lastname: Devidas
authors.forename: H E
authors.initials: HE
authors.lastname: Grier
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D011300:Preoperative Care; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate