title: Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer.
abstract: We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.
authors.affiliation: Baylor Charles A. Sammons Cancer Center, Dallas, Texas 75246, USA. joyce.o'shaughnessy@usoncology.com
authors.forename: Joyce A
authors.initials: JA
authors.lastname: O'Shaughnessy
authors.forename: Sasha
authors.initials: S
authors.lastname: Vukelja
authors.forename: Thomas
authors.initials: T
authors.lastname: Marsland
authors.forename: Gary
authors.initials: G
authors.lastname: Kimmel
authors.forename: Suresh
authors.initials: S
authors.lastname: Ratnam
authors.forename: John E
authors.initials: JE
authors.lastname: Pippen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008408:Mastectomy / Q000379:methods; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011336:Probability; D012307:Risk Factors; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068878:Trastuzumab; D000093542:Gemcitabine