14 CLINICAL STUDIES
14.1 Adjuvant Breast Cancer
The efficacy of doxorubicin hydrochloride-containing regimens for the post-operative, adjuvant treatment of surgically resected breast cancer was evaluated in a meta-analysis conducted by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). The EBCTCG meta-analyses compared cyclophosphamide, methotrexate, and fluorouracil (CMF) to no chemotherapy (19 trials including 7523 patients) and doxorubicin hydrochloride-containing regimens with CMF as an active control (6 trials including 3510 patients). Data from the meta-analysis of trials comparing CMF to no therapy were used to establish the historical treatment effect size for CMF regimens. The major efficacy outcome measures were disease-free survival (DFS) and overall survival (OS).
Of the 3510 women (2157 received doxorubicin hydrochloride-containing regimens and 1353 received CMF treatment) with early breast cancer involving axillary lymph nodes included in the six trials from the meta-analyses, approximately 70% were premenopausal and 30% were postmenopausal.
At the time of the meta-analysis, 1745 first recurrences and 1348 deaths had occurred. The analyses demonstrated that doxorubicin hydrochloride-containing regimens retained at least 75% of the historical CMF adjuvant effect on DFS with a hazard ratio (HR) of 0.91 (95% CI: 0.82, 1.01) and on OS with a HR of 0.91 (95% CI: 0.81, 1.03). Efficacy results are provided in Table 3 and Figures 1 and 2.
Study (starting year) | Regimens | No. of Cycles | No. of Patients | Doxorubicin Hydrochloride-Containing Regimens vs. CMF HR* (95% CI) | |
---|---|---|---|---|---|
DFS | OS | ||||
Abbreviations: DFS = disease free survival; OS = overall survival; AC = doxorubicin hydrochloride, cyclophosphamide; AVbCMF = doxorubicin hydrochloride, vinblastine, cyclophosphamide, methotrexate, fluorouracil; CMF = cyclophosphamide, methotrexate, fluorouracil; CMFVA = cyclophosphamide, methotrexate, fluorouracil, vincristine, doxorubicin hydrochloride; FAC = fluorouracil, doxorubicin hydrochloride, cyclophosphamide; FACV = fluorouracil, doxorubicin hydrochloride, cyclophosphamide, vincristine; HR = hazard ratio; CI = confidence interval | |||||
| |||||
NSABP B-15 (1984) | AC | 4 | 1562† | 0.93 (0.82, 1.06) | 0.97 (0.83, 1.12) |
CMF | 6 | 776 | |||
SECSG 2 (1976) | FAC | 6 | 260 | 0.86 (0.66, 1.13) | 0.93 (0.69, 1.26) |
CMF | 6 | 268 | |||
ONCOFRANCE (1978) | FACV | 12 | 138 | 0.71 (0.49, 1.03) | 0.65 (0.44, 0.96) |
CMF | 12 | 113 | |||
SE Sweden BCG A (1980) | AC | 6 | 21 | 0.59 (0.22, 1.61) | 0.53 (0.21, 1.37) |
CMF | 6 | 22 | |||
NSABC Israel Br0283 (1983) | AVbCMF‡ | 4 6 | 55 | 0.91 (0.53, 1.57) | 0.88 (0.47, 1.63) |
CMF | 6 | 50 | |||
Austrian BCSG 3 (1984) | CMFVA | 6 | 121 | 1.07 (0.73, 1.55) | 0.93 (0.64, 1.35) |
CMF | 8 | 124 | |||
Combined Studies | Doxorubicin Hydrochloride-Containing Regimen | 2157 | 0.91 (0.82, 1.01) | 0.91 (0.81, 1.03) | |
CMF | 1353 |
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