Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012

Abstract

Purpose: Patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC) were randomly assigned to 21-day doxorubicin and cyclophosphamide administered for five cycles (standard arm) versus weekly doxorubicin and daily oral cyclophosphamide administered with granulocyte colony-stimulating factor support for 15 weeks (continuous arm). All patients had subsequent weekly paclitaxel for 12 weeks before surgery.

Patients and methods: Patients (n = 372) were randomly assigned to the standard arm (n = 186) or the continuous arm (n = 186) stratified by disease type (LABC, n = 256; IBC, n = 116). The primary outcome was microscopic pathologic complete response (pCR) at surgery. Secondary outcomes included disease-free survival, overall survival, and toxicity.

Results: More patients in the standard arm had grade 3 to 4 leukopenia and neutropenia, but there were more instances of stomatitis/pharyngitis and hand-foot skin reaction in the continuous arm. Assessed among 356 eligible patients, pCR was not different between the treatment groups stratified by disease type (P = .42). In subset analysis, higher pCR rates were observed in the continuous arm versus the standard arm only for stage IIIB disease (P = .0057) and in IBC (P = .06). Comparison of overall survival and disease-free survival showed no difference between treatment groups (P = .37 and P = .87, respectively).

Conclusion: No significant clinical benefit was seen for the investigational arm in this trial overall.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT flow diagram. All 372 patients randomly allocated after the protocol amendment to include taxane treatment are shown.

Fig 2.

Pathologic complete response (pCR) rates overall and by subgroup. Rates and associated two-sided P value for the comparison of the standard arm (Std) to the continuous therapy arm (Cont) are shown for the group overall, then by disease type (inflammatory breast cancer [IBC] or locally advanced breast cancer [LABC]), and then by hormone receptor (HR) status. Neg, negative; Pos, positive.

Fig 3.

Disease-free survival by treatment group by disease subtype. The graphs show Kaplan-Meier estimates of disease-free survival from time of registration to progression, disease recurrence, or death as a result of any cause. The log-rank P values compare the two randomized arms within disease subtype. (A) Inflammatory breast cancer and (B) locally advanced breast cancer.

Fig 4.

Overall survival by treatment group by disease subtype. The graphs show Kaplan-Meier estimates of overall survival from time of registration to death as a result of any cause. The log-rank P values compare the two randomized arms within disease subtype. (A) Inflammatory breast cancer and (B) locally advanced breast cancer.