title: A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients.
abstract: This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m(-2)) and cyclophosphamide (2 g m(-2)) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m(-2) and thiotepa 200 mg m(-2). At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m(-2) cyclophosphamide and 400 mg m(-2) thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immunosuppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.
authors.affiliation: Département de Cancérologie Médicale Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cedex, France. Bachelot@lyon.fnclcc.fr
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.forename: F
authors.initials: F
authors.lastname: Gomez
authors.forename: P
authors.initials: P
authors.lastname: Biron
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: P
authors.initials: P
authors.lastname: Soler-Michel
authors.forename: I
authors.initials: I
authors.lastname: Philip
authors.forename: J P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: P
authors.initials: P
authors.lastname: Rebattu
authors.forename: A
authors.initials: A
authors.lastname: Dumortier
authors.forename: J P
authors.initials: JP
authors.lastname: Droz
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D013852:Thiotepa / Q000008:administration & dosage*
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa