title: Dose intensification of mitoxantrone in combination with paclitaxel in advanced breast cancer: a phase II study.
abstract: BACKGROUND
  Paclitaxel and mitoxantrone are highly active agents in the treatment of advanced breast cancer (ABC). This study evaluated the combination of paclitaxel and mitoxantrone in patients with advanced breast cancer to determine activity and toxicity.
  
  
  METHODS
  42 patients with ABC were treated with paclitaxel at a fixed dose of 175 mg/m2 intravenous (IV) by a 3-hour infusion on day 1, while mitoxantrone was given by 2 mg/m2 increments, starting from 10 mg/m2 by bolus IV injection on day 1 after paclitaxel. Cycles were repeated every 3 weeks. Mitoxantrone doses were increased if the maximum tolerated dose (MTD) had not been reached.
  
  
  RESULTS
  The overall response rate (CR + PR) was 69% (CI 95%: 55-83). Six (14%) patients obtained CR and 23 (55%) PR with a median duration of response of 8 months (range 2-16). There were no differences in response rates (RR) between the three levels of mitoxantrone. Median time to failure and survival were 7 months (range 1-26) and 12 months (range 2-29), respectively. After 12 months 14 (33%) patients had died and 8 (19%) patients were alive after 18 months. MTD was reached at 14 mg/m2 level of mitoxantrone. Leukopenia was evident in 39 (93%) of total patients and was severe in 28 (67%) patients. All non-hematological toxicity observed was mild.
  
  
  CONCLUSIONS
  This trial shows the activity of paclitaxel and mitoxantrone in ABC and finds that a dose of 14 mg/m2 of mitoxantrone is the MTD in combination with a fixed dose of 175 mg/m2 of paclitaxel without granulocyte colony stimulating factor (G-CSF).
authors.affiliation: Department of Internal Medicine and Oncology, University Hospital, Terni, Italy. dicostanzo@sirio-oncology.it
authors.forename: F D
authors.initials: FD
authors.lastname: Costanzo
authors.forename: A
authors.initials: A
authors.lastname: Sdrobolini
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: D
authors.initials: D
authors.lastname: Bilancia
authors.forename: L
authors.initials: L
authors.lastname: Acito
authors.forename: S
authors.initials: S
authors.lastname: Gasperoni
authors.forename: L
authors.initials: L
authors.lastname: Valenti
authors.forename: L
authors.initials: L
authors.lastname: Fioriti
authors.forename: S
authors.initials: S
authors.lastname: Angiona
authors.forename: L
authors.initials: L
authors.lastname: Giustini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D008942:Mitoxantrone; D017239:Paclitaxel