title: Hypofractionated accelerated radiotherapy with cytoprotection combined with trastuzumab, liposomal doxorubicine, and docetaxel in c-erbB-2-positive breast cancer.
abstract: OBJECTIVE
  Trastuzumab, an antic-erbB-2 monoclonal antibody, has become a standard component of chemotherapy for c-erbB-2-positive advanced breast carcinoma. Despite the experimental evidence of its radiosensitizing properties, trastuzumab has never been used in combination with radiotherapy for the treatment of patients with locally advanced disease.
  
  
  METHODS
  Twenty-two patients with c-erbB-2-positive locally advanced chemoresistant (7 patients) or with high-risk breast cancer (15 patients) were recruited in a treatment protocol combining hypofractionated/accelerated radiotherapy (hypoARC) supported with high-dose amifostine (1000 mg subcutaneous), concurrently with trastuzumab (4 mg/kg every 2 weeks). Thirteen of these patients (including all 7 inoperable cases) received concurrently chemotherapy with liposomal doxorubicin and docetaxel (25 mg/m2 and 40 mg/m2 every 2 weeks, respectively).
  
  
  RESULTS
  Administration of trastuzumab together with highly accelerated amifostine-supported radiotherapy was feasible without an increase in early and late radiation toxicity. This was obtained despite the concurrent administration of aggressive chemotherapy. Complete responses were noted in 5 of 7 patients with locally, often far advanced, chemoresistant disease. None of the complete responders or the 15 high-risk breast cancer patients relapsed within the 3- to 26-month follow-up period.
  
  
  CONCLUSIONS
  Inclusion of trastuzumab in the radiochemotherapy protocols for breast cancer does not increase radiation or systemic toxicity. The concurrent administration of aggressive radiotherapy with docetaxel and liposomal doxorubicin is feasible when supported with amifostine. The value of such regimens in the treatment of locally advanced or high risk c-erbB-2 positive breast cancer patients deserves further evaluation.
authors.affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: John
authors.initials: J
authors.lastname: Manavis
authors.forename: Costantinos
authors.initials: C
authors.lastname: Simopoulos
authors.forename: Vasilis
authors.initials: V
authors.lastname: Liberis
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D004317:Doxorubicin; D004337:Drug Carriers; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab