title: Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel.
abstract: BACKGROUND
  Some chemotherapy (CT) drugs, including taxanes, may enhance the effectiveness of radiation therapy (RT). However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel.
  
  
  METHODS
  Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation pneumonitis was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was estimated. The Cox proportional hazards model was used to find covariates that may be associated with the observed outcomes. All P values were two-sided.
  
  
  RESULTS
  Radiation pneumonitis developed in six of the 41 patients. Three patients received paclitaxel concurrently with RT, and three received it sequentially (P =.95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P =.6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was 1.1% (95% CI = 0.2% to 2.3%). The difference between the crude rates with or without paclitaxel is highly statistically significant (P<.0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P =.002).
  
  
  CONCLUSIONS
  The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence of radiation pneumonitis.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA. ataghian@partners.org
authors.forename: A G
authors.initials: AG
authors.lastname: Taghian
authors.forename: S I
authors.initials: SI
authors.lastname: Assaad
authors.forename: A
authors.initials: A
authors.lastname: Niemierko
authors.forename: I
authors.initials: I
authors.lastname: Kuter
authors.forename: J
authors.initials: J
authors.lastname: Younger
authors.forename: R
authors.initials: R
authors.lastname: Schoenthaler
authors.forename: M
authors.initials: M
authors.lastname: Roche
authors.forename: S N
authors.initials: SN
authors.lastname: Powell
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000528:radiation effects; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011014:Pneumonia / Q000150:complications* / Q000517:prevention & control*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel