title: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
abstract: OBJECTIVE
  The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas.
  
  
  METHODS
  This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C).
  
  
  RESULTS
  The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar.
  
  
  CONCLUSIONS
  In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
authors.affiliation: Divisione Oncologia Medica A, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: T
authors.initials: T
authors.lastname: Tursz
authors.forename: H
authors.initials: H
authors.lastname: Mouridsen
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: W
authors.initials: W
authors.lastname: Steward
authors.forename: R
authors.initials: R
authors.lastname: Somers
authors.forename: J
authors.initials: J
authors.lastname: Buesa
authors.forename: P
authors.initials: P
authors.lastname: Casali
authors.forename: D
authors.initials: D
authors.lastname: Spooner
authors.forename: E
authors.initials: E
authors.lastname: Rankin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide