title: Phase I study of twelve-day prolonged infusion of high-dose ifosfamide and doxorubicin as first-line chemotherapy in adult patients with advanced soft tissue sarcomas.
abstract: OBJECTIVE
  To determine whether a prolonged 12-day continuous infusion allows the administration of high-dose ifosfamide (IFO) with an acceptable toxicity profile when combined with full-dose doxorubicin (Adriamycin; ADM) as first-line chemotherapy in patients with advanced soft tissue sarcomas.
  
  
  METHODS
  Escalating doses of continuous infusion IFO (8-15 g/m2) given on days 1 to 12 in combination with ADM 75 mg/m2 given on day 8 and prophylactic granulocyte colony-stimulating factor support were administered every 4 weeks to 35 chemonaïve patients with advanced soft tissue sarcomas.
  
  
  RESULTS
  The maximum tolerated dose was IFO 15 g/m2. Hematological toxicity was the main dose-limiting toxicity and was dose dependent. Furthermore, thrombocytopenia was cumulative. Grade 4 (WHO) neutropenia and thrombocytopenia were recorded in 48% and 14% of courses, respectively. Eight patients experienced febrile neutropenia. A partial response was observed in 16 out of 30 assessable patients [53%, 95% confidence interval (CI) 25-63]; median time to progression was 25 weeks (range 4-91).
  
  
  CONCLUSIONS
  This study proved that a prolonged 12-day continuous infusion allows an increase in the total IFO dose that can be safely combined with ADM. A multicentric phase II study by the Italian Sarcoma Group to assess its antitumor activity is currently ongoing in patients with advanced soft tissue sarcomas.
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy. tommaso.de-pas@ieo.it
authors.forename: T
authors.initials: T
authors.lastname: De Pas
authors.forename: G
authors.initials: G
authors.lastname: Curigliano
authors.forename: G
authors.initials: G
authors.lastname: Masci
authors.forename: C
authors.initials: C
authors.lastname: Catania
authors.forename: A
authors.initials: A
authors.lastname: Comandone
authors.forename: C
authors.initials: C
authors.lastname: Boni
authors.forename: A
authors.initials: A
authors.lastname: Tucci
authors.forename: O
authors.initials: O
authors.lastname: Pagani
authors.forename: E
authors.initials: E
authors.lastname: Marrocco
authors.forename: F
authors.initials: F
authors.lastname: de Braud
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; 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 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D007069:Ifosfamide