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.

• Authors: Georgiana K Ellis, William E Barlow, Julie R Gralow, Gabriel N Hortobagyi, Christy A Russell, Melanie E Royce, Edith A Perez, Danika Lew, Robert B Livingston
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 8 Pg. 1014-21 (Mar 10 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21220618 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Granulocyte Colony-Stimulating Factor
• Doxorubicin
• Cyclophosphamide
• Paclitaxel

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (chemistry, drug therapy, mortality, pathology, surgery)
• Chemotherapy, Adjuvant
• Chi-Square Distribution
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Odds Ratio
• Paclitaxel (administration & dosage)
• Proportional Hazards Models
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome
• United States
• Young Adult