Randomized Study Comparing Adjuvant Radiotherapy (RT) with Concomitant Chemotherapy (CT) Versus Sequential Treatment After Conservative Surgery for Patients with Stages I and II Breast Carcinoma

Reviewer: Roberto Santiago, MD
Last Modified: October 9, 2002

Presenter: Gilles. Calais
Presenter's Affiliation: Department of Oncology Radiotherapy, CHU, Tours, France
Type of Session: Scientific


    Both whole breast irradiation and chemotherapy are often indicated after conservative surgery for early stage breast cancer. However, the sequencing of CT and RT after conservative surgery in this group is controversial. Studies have suggested an advantage to give CT followed by RT rather than RT followed by CT because of the high risk of systemic metastases. On the other hand, an increased risk of local recurrence has been observed when radiation is delayed. Several phase II studies have indicated that concomitant administration of the two treatments is feasible using selected drugs that may not have cumulative toxic effects with RT. This study compares (multicenter phase III trial) the efficacy of sequential treatment with CT first followed by RT (arm A) versus CT administered concurrently with RT (arm B) in patients with early stage breast cancer who have undergone conservative surgery with axillary dissection.

Materials and Methods

  • Between February 1996 and April 2000, 706 patients were entered from 28 centers and then stratified according to the axillary status.
  • The CT regimen consisted of Mitoxantrone (12 mg/m2), 5FU (500 mg/m2) and Cyclophosphamide (500 mg/2) for 6 cycles of 21 days in both arms. Mitoxantrone was chosen because is the only member of the anthracycline family that does not produces free radicals and therefore has less chances of increasing the toxicity of RT.
  • RT delivered 50 Gy in 5 weeks to the whole breast followed by a 10 to 20 Gy boost to the tumor bed with electrons or brachytherapy. The subclavicular area was irradiated when axillary dissection was positive.
  • The RT In arm B was delivered concurrently with the first 3 cycles of CT. In arm A, radiation was started 3 to 5 weeks after the 6th cycle of CT.


  • Forty four percent of patients were node negative. The 2 arms were equally balanced regarding to age, stage, performance status, histology, hormonal receptors, tumor margins, in situ component and axillary status.
  • Mean time to initiate RT was 170 days in arm A and 39 days in arm B (p<0.0001).
  • RT compliance was similar in the 2 arms regarding to total dose, treatment duration and treatment interruption. Treatment interruptions occurred in 18% of patients of each arm.
  • Compliance to CT was comparable. The mean relative dose intensity of CT in arm A was 95% and 92% in arm B.
  • Grade >1 esophagitis rate was significantly higher in arm B (23% versus 7%) but only a few patients experienced severe esophagitis. Haematologic toxicity (neutrophil count and hemoglobin level) was higher in arm B. Incidence of other acute toxic effects including skin toxicity were similar in the 2 arms.
  • The median follow-up of the study is 40 months.
  • Two patients developed acute leukemia (one in each arm).
  • The local-regional recurrence and disease-free survival rates were respectively 4.3% versus 3.5% and 82% versus 83% in arm A versus B.
  • No differences were observed regarding overall survival or the incidence of distant metastases or second primary tumor.
  • For node-positive patients the incidence of local recurrence was 7.6% in arm A and 3.8% in arm B (p=0.054).

Author's Conclusions

  • The early results suggest that the concomitant administration of CT and RT using selected drugs is slightly difficult because of moderate enhancement of acute toxiciy.
  • An advantage of this technique is an overall reduction on treatment time.
  • Longer follow-up is needed to determine the impact of this strategy on local control and or survival.

Clinical/Scientific Implications

    Although longer follow-up is needed to make conclusions about the role of this strategy on future BCT practices, similar approaches attempting to decrease the overall treatment time and minimizing the delay of consolidative local therapy at the expense of systemic therapy are theoretically appealing and deserve further investigation.

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