title: Paclitaxel combined with ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer: activity independence of prior docetaxel resistance.
abstract: BACKGROUND
  We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC).
  
  
  METHODS
  Patients received paclitaxel (175 mg/m(2) i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m(2) i.v. in a 15-min infusion) on days 1-3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles.
  
  
  RESULTS
  We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths.
  
  
  CONCLUSIONS
  Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.
authors.affiliation: Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul, 120-752, Korea.
authors.forename: Yong Wha
authors.initials: YW
authors.lastname: Moon
authors.forename: Joo Hyuk
authors.initials: JH
authors.lastname: Sohn
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Hyun
authors.initials: H
authors.lastname: Chang
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Park
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Seho
authors.initials: S
authors.lastname: Park
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
authors.forename: Yong Tai
authors.initials: YT
authors.lastname: Kim
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D007069:Ifosfamide