title: A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer.
abstract: BACKGROUND
  SRC plays an important role in the pathogenesis of metastatic breast cancer (MBC). In preclinical models, paclitaxel and the oral SRC inhibitor dasatinib showed greater antitumor activity than either agent. To determine the maximum tolerated dose of this combination, we conducted a phase I study.
  
  
  METHODS
  Patients with MBC; Eastern Cooperative Oncology Group performance status of zero to one; normal hepatic, renal and marrow function were eligible. Paclitaxel 80 mg/m(2) was given 3 weeks of 4. The starting dasatinib dose was 70 mg and was increased, using a standard 3 + 3 dose-escalation scheme.
  
  
  RESULTS
  Fifteen patients enrolled (median age 54 years, range 35-74). No dose-limiting toxic effects (DLTs) occurred at dasatinib doses of 70-120 mg. One DLT (grade 3 fatigue) occurred in the dasatinib 150-mg cohort, which was expanded (six patients) with no further DLTs. However, due to cumulative toxic effects (rash, fatigue, diarrhea), the recommended phase II dose is dasatinib 120 mg. Of 13 assessable patients, a partial response was seen in 4 patients (31%), including 2 patients previously treated with taxanes; all received ≥120 mg dasatinib. An additional five patients (29%) had stable disease.
  
  
  CONCLUSIONS
  In combination with weekly paclitaxel, the recommended phase II dose of dasatinib is 120 mg daily and preliminary activity has been seen in patients with MBC.
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: M N
authors.initials: MN
authors.lastname: Fornier
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York. Electronic address: morrisp1@mskcc.org.
authors.forename: P G
authors.initials: PG
authors.lastname: Morris
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: A
authors.initials: A
authors.lastname: Abbruzzi
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: G
authors.initials: G
authors.lastname: D'Andrea
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: J
authors.initials: J
authors.lastname: Bromberg
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: C
authors.initials: C
authors.lastname: Dang
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: M
authors.initials: M
authors.lastname: Dickler
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: S
authors.initials: S
authors.lastname: Modi
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: N
authors.initials: N
authors.lastname: Sklarin
authors.affiliation: Breast Center, Baylor College of Medicine, Houston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.affiliation: Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000473:pathology; D000069439:Dasatinib; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D016066:Pleural Effusion, Malignant / Q000139:chemically induced; D011743:Pyrimidines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011743:Pyrimidines; D013844:Thiazoles; D017239:Paclitaxel; D000069439:Dasatinib