Annals of Oncology 4:295-301, 1993
© 1993 European Society for Medical Oncology
research-article |
Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients
1Department of Internal Medicine, Section Haematology-Oncology, Academic Hospital Maastricht
2Department of Internal Medicine, St. Laurentius Hospital Roermond
3Department of Statistics, University of Limburg Maastricht
4Department of Registration, Integraal Kankercentrum Limburg Maastricht
5Department of Internal Medicine, De Wever Hospital Heerlen
6Department of Internal Medicine, Maaslandhospital Sittard
7Radiotherapeutisch Instituut Limburg Heerlen, The Netherlands
8Medical Department, Farmitalia Carlo Erba Benelux Brussels, Belgium
9Department of Internal Medicine, Academic Hospital Utrecht, The Netherlands
Correspondence to: Pierre S. Hupperets, M.D., Department of Internal Medicine, Section Haematology-Oncology, Academic Hospital Maastricht, P.O. Box 5800, 6202 ZA Maastricht, The Netherlands
BACKGROUND:: The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling
PATIENTS AND METHODS:: Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (Tl-3, Nl) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA– arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d / 28 days, followed by 500 mg i.m. twice weekly during 5 months.
RESULTS:: The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA– group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p – 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA– group (p = 0.12). Patients >>60 years benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p – 0.18), but within subgroups analysed there was an advantage for MPA+ in patients > 55 years (p – 0.002) and in pTl patients (p – 0.045).
CONCLUSIONS:: High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients.
adjuvant chemohormonal therapy, breast cancer, medroxyprogesterone acetate