A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22

• Published in: SpringerPlus Vol. 4; no. 1; p. 631
• Main Authors: Trudeau, Maureen Elizabeth, Chapman, Judith-Anne W., Guo, Baoqing, Clemons, Mark J., Dent, Rebecca A., Jong, Roberta A., Kahn, Harriette J., Pritchard, Kathleen I., Han, Lei, O’Brien, Patti, Shepherd, Lois E., Parissenti, Amadeo M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 21-10-2015; Springer Nature B.V
• Subjects: Humanities and Social Sciences; Medicine; multidisciplinary; Science; Science (multidisciplinary); Response biomarkers; Epirubicin; Microarray; LABC; Phase I/II; Docetaxel
• ISSN: 2193-1801; 2193-1801
• DOI: 10.1186/s40064-015-1392-x

This phase I/II neoadjuvant trial (ClinicalTrials.gov identifier NCT00066443) determined maximally-tolerated doses (MTD), dose-limiting toxicities, response-to-therapy, and explored the role of novel response biomarkers. MA.22 accrued T3N0, any N2 or N3, and T4 breast cancer patients. Treatment was 6 cycles of 3-weekly (Schedule A; N = 47) or 8 cycles of 2-weekly (Schedule B; N = 46) epirubicin/docetaxel chemotherapy in sequential phase I/II studies, with growth factor support. In phase I of each schedule, MTDs were based on DLT. In phase II, clinical responses (CR/PR) and pathologic complete responses (pCR) were assessed. Tumor biopsy cores were obtained pre-, mid-, and post-treatment: 3 for pathologic assessment; 3 for microarray studies. DLT for Schedule A was febrile neutropenia at 105 mg/m
2
epirubicin and 75 mg/m
2
docetaxel; for schedule B, it was fatigue at 75 mg/m
2
for both agents. Phase II doses were 90 mg/m
2
epirubicin/75 mg/m
2
docetaxel for Schedule A and 60 mg/m
2
(both agents) for Schedule B. Schedule A CR/PR and pCR rates were 90 and 10 %, with large reductions in tumor RNA content and integrity following treatment; Schedule B results were 93 and 0 %, with smaller reductions in RNA quality. Pre-treatment expression of several genes was associated with clinical response, including those within a likely amplicon at 17q12 (ERBB2, TCAP, GSDMB, and PNMT). The combination regimens had acceptable toxicity, good clinical response, induction of changes in tumor RNA content and integrity. Pre-treatment expression of particular genes was associated with clinical responses, including several near 17q12, which with ERBB2, may better identify chemoresponsiveness.