A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results.
OBJECTIVE
To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients.


METHODS
This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles.


RESULTS
Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02).


CONCLUSIONS
Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.
Rouëssé
Jacques
J
Centre René Huguenin, Saint-Cloud, France. j.rouesse@stcloud-huguenin.org
de la Lande
Brigitte
B
Bertheault-Cvitkovic
Frédérique
F
Serin
Daniel
D
Graïc
Yvon
Y
Combe
Martin
M
Leduc
Bernard
B
Lucas
Virginie
V
Demange
Liliane
L
Nguyen
Tan Dat
TD
Castèra
Daniel
D
Krzisch
Claude
C
Villet
Richard
R
Mouret-Fourme
Emmanuelle
E
Garbay
Jean-Rémy
JR
Noguès
Catherine
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000145:classification; D018714:Radiotherapy, Adjuvant
D015251:Epirubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D005472:Fluorouracil