title: Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.
abstract: Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.
authors.affiliation: Centre Pluridisciplinaire d'Oncologie, University Hospital, CHUV BH06, Rue du Bugnon 46, Lausanne, Switzerland. Serge.Leyvraz@chuv.ch
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: L
authors.initials: L
authors.lastname: Guillou
authors.forename: H P
authors.initials: HP
authors.lastname: Honegger
authors.forename: A
authors.initials: A
authors.lastname: Christinat
authors.forename: M F
authors.initials: MF
authors.lastname: Fey
authors.forename: C
authors.initials: C
authors.lastname: Sessa
authors.forename: M
authors.initials: M
authors.lastname: Wernli
authors.forename: T
authors.initials: T
authors.lastname: Cerny
authors.forename: D
authors.initials: D
authors.lastname: Dietrich
authors.forename: B
authors.initials: B
authors.lastname: Pestalozzi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D016879:Salvage Therapy; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D007069:Ifosfamide