DOXORUBICIN (doxorubicin hydrochloride) Clinical Studies

(doxorubicin hydrochloride)

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Clinical Studies

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.

Table 3. Summary of Randomized Trials Comparing Doxorubicin Hydrochloride-Containing Regimens Versus CMF in Meta-Analysis
Study (starting year)	Regimens	No. of Cycles	No. of Patients	Doxorubicin Hydrochloride-Containing Regimens vs. CMF HR* (95% CI)
Study (starting year)	Regimens	No. of Cycles	No. of Patients	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
* Hazard ratio of less than 1 indicates that the treatment with doxorubicin hydrochloride-containing regimens is associated with lower risk of disease recurrences or death compared to the treatment with CMF. † Includes pooled data from patients who received either AC alone for 4 cycles, or who were treated with AC for 4 cycles followed by 3 cycles of CMF. ‡ Patients received alternating cycles of AVb and CMF.
NSABP B-15 (1984)	AC	4	1562†	0.93 (0.82, 1.06)	0.97 (0.83, 1.12)
NSABP B-15 (1984)	CMF	6	776
SECSG 2 (1976)	FAC	6	260	0.86 (0.66, 1.13)	0.93 (0.69, 1.26)
SECSG 2 (1976)	CMF	6	268
ONCOFRANCE (1978)	FACV	12	138	0.71 (0.49, 1.03)	0.65 (0.44, 0.96)
ONCOFRANCE (1978)	CMF	12	113
SE Sweden BCG A (1980)	AC	6	21	0.59 (0.22, 1.61)	0.53 (0.21, 1.37)
SE Sweden BCG A (1980)	CMF	6	22
NSABC Israel Br0283 (1983)	AVbCMF‡	4 6	55	0.91 (0.53, 1.57)	0.88 (0.47, 1.63)
NSABC Israel Br0283 (1983)	CMF	6	50
Austrian BCSG 3 (1984)	CMFVA	6	121	1.07 (0.73, 1.55)	0.93 (0.64, 1.35)
Austrian BCSG 3 (1984)	CMF	8	124
Combined Studies	Doxorubicin Hydrochloride-Containing Regimen		2157	0.91 (0.82, 1.01)	0.91 (0.81, 1.03)
Combined Studies	CMF		1353	0.91 (0.82, 1.01)	0.91 (0.81, 1.03)

Figure 1. Meta-analysis of Disease-Free Survival

Figure 2. Meta-analysis of Overall Survival

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