title: Phase I/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer.
abstract: The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m(-2) intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m(-2) intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m(-2) gemcitabine and 10 mg m(-2) mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m(-2) and mitoxantrone at 10 mg m(-2), 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2-33), and median survival was 42 weeks (range, 2-92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m(-2) (day 1) for mitoxantrone and 1000 mg m(-2) for gemcitabine (days 1-8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted.
authors.affiliation: Operative Unit of Medical Oncology, Oncology Institute, Bari, Italy. vitolorusso@inwind.it
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: E
authors.initials: E
authors.lastname: Crucitta
authors.forename: N
authors.initials: N
authors.lastname: Silvestris
authors.forename: A
authors.initials: A
authors.lastname: Catino
authors.forename: L
authors.initials: L
authors.lastname: Caporusso
authors.forename: A
authors.initials: A
authors.lastname: Mazzei
authors.forename: M
authors.initials: M
authors.lastname: Guida
authors.forename: A
authors.initials: A
authors.lastname: Latorre
authors.forename: D
authors.initials: D
authors.lastname: Sambiasi
authors.forename: C
authors.initials: C
authors.lastname: D'Amico
authors.forename: F
authors.initials: F
authors.lastname: Schittulli
authors.forename: P
authors.initials: P
authors.lastname: Calabrese
authors.forename: M
authors.initials: M
authors.lastname: De Lena
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000150:complications; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D016879:Salvage Therapy / Q000009:adverse effects; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000556:secondary; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D008942:Mitoxantrone; D000093542:Gemcitabine