Concurrent Neoadjuvant Chemotherapy and Radiation Therapy in Locally Advanced Breast Cancer

Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):769-776. doi: 10.1016/j.ijrobp.2017.06.005. Epub 2017 Jun 20.

Abstract

Purpose: To evaluate whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathologic complete response (pCR) to treatment for locally advanced breast cancer (LABC).

Methods and materials: This prospective phase 2 trial recruited 32 LABC patients from 2009 to 2011. Patients received neoadjuvant every-3-weekly 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) for 3 cycles, followed by weekly docetaxel (35 mg/m2) for 9 cycles. Regional radiation (45 Gy/25 plus 5.4 Gy/5) was delivered concurrently with docetaxel, then modified radical mastectomy. Patients were matched post hoc by a blinded statistician to a concurrent cohort treated with neoadjuvant chemotherapy, modified radical mastectomy, and adjuvant regional radiation.

Results: Thirty of 32 patients completed treatment. Twenty-seven were successfully matched by propensity score to 81 control patients by age, stage, and molecular subtype. The concurrent chemoradiation produced a significant increase in pCR (14% vs 22%, P<.001) but no statistically significant difference in disease-free and overall survival at 3 years (respectively, 69% vs 81%, P=.186, hazard ratio 0.51; and 74% vs 89%, P=.162, hazard ratio 0.46). Toxicity included 25% of patients with grade 3 pneumonitis and 25% of patients with dermatitis, and 1 death.

Conclusions: Concurrent neoadjuvant radiation added to radiosensitizing chemotherapy significantly improved pCR. A prospective randomized clinical trial is warranted to exploit the improved response seen with concurrent therapy but using another radio-sensitizing taxane, to better minimize treatment-related toxicity and determine its impact on overall survival.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Chemotherapy, Adjuvant / methods
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Mastectomy, Modified Radical
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Propensity Score
  • Prospective Studies
  • Radiation-Sensitizing Agents / therapeutic use*
  • Taxoids / administration & dosage

Substances

  • Radiation-Sensitizing Agents
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Dexamethasone
  • Cyclophosphamide
  • Fluorouracil