title: Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas.
abstract: A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Toma
authors.forename: R
authors.initials: R
authors.lastname: Palumbo
authors.forename: G
authors.initials: G
authors.lastname: Canavese
authors.forename: E
authors.initials: E
authors.lastname: Albanese
authors.forename: E
authors.initials: E
authors.lastname: Cantoni
authors.forename: A
authors.initials: A
authors.lastname: Barisone
authors.forename: G
authors.initials: G
authors.lastname: Reggiardo
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: L
authors.initials: L
authors.lastname: Santi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D007069:Ifosfamide