title: Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer.
abstract: OBJECTIVE
  There is concern that breast cancer patients treated with left-sided radiation therapy (XRT) and doxorubicin (DOX) may have an increased risk of cardiac toxicity. In addition, the effect of different sequencing of XRT and chemotherapy (CT) on the likelihood of cardiotoxicity, as well as cellulitis, arm edema, or brachial plexopathy, is not well understood. We reviewed the records of patients treated on a randomized trial testing the sequencing of CT and XRT to determine if there was an increase in cardiac events or other complications in patients treated with a total dose of DOX of 180 mg/m2 and XRT, comparing patients with treatment to the left breast and the right breast, and comparing patients treated with initial CT and initial RT.
  
  
  METHODS
  From June 1984 to December 1992, 244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive CT (4 cycles of CAMFP at 3 week intervals) either before or after XRT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional). Two hundred thirty-one patients were evaluable for the development of cardiac toxicity. The median age at diagnosis was 45 years (range, 20-68). CT doses were: doxorubicin, 45 mg/m2 IV bolus, d 3; methotrexate, 200 mg/m2 IV, d 1 and 15; 5-fluorouracil, 500 mg/m2 IV, d 1; cyclophosphamide, 500 mg/m2 IV, d 1; prednisone 40 mg p.o., d 1-5. A cardiac event was defined as a myocardial infarction or clinical evidence of congestive heart failure. Median follow-up time was 53 months.
  
  
  RESULTS
  No cardiac events were observed for patients with either left- or right-sided breast cancer. The sequencing of CT and XRT had no significant effect on the risk of cardiac toxicity, cellulitis, arm edema or brachial plexopathy.
  
  
  CONCLUSIONS
  We observed no evidence of an increased risk of cardiac toxicity from the addition of left breast tangential irradiation to DOX at a total dose of 180 mg/m2. Additional follow-up is needed to exclude possible late events. In addition, the sequencing of CT and XRT does not appear to affect the risk of cellulitis, arm edema, or brachial plexopathy.
authors.affiliation: Joint Center for Radiation Therapy, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Hardenbergh
authors.forename: A
authors.initials: A
authors.lastname: Recht
authors.forename: S
authors.initials: S
authors.lastname: Gollamudi
authors.forename: S E
authors.initials: SE
authors.lastname: Come
authors.forename: D F
authors.initials: DF
authors.lastname: Hayes
authors.forename: L N
authors.initials: LN
authors.lastname: Shulman
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: R S
authors.initials: RS
authors.lastname: Gelman
authors.forename: B
authors.initials: B
authors.lastname: Silver
authors.forename: J R
authors.initials: JR
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001132:Arm; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004487:Edema / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate