Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment.
OBJECTIVE
To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR).


METHODS
One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy.


RESULTS
Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models.


CONCLUSIONS
There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.
Falkson
G
G
University of Pretoria, South Africa. gfalkson@medic.up.ac.za
Gelman
R S
RS
Pandya
K J
KJ
Osborne
C K
CK
Tormey
D
D
Cummings
F J
FJ
Sledge
G W
GW
Abeloff
M D
MD
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005474:Fluoxymesterone / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
D013629:Tamoxifen; D003520:Cyclophosphamide; D005474:Fluoxymesterone; D005472:Fluorouracil; D011241:Prednisone; D008727:Methotrexate