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. 2015 Oct 21:4:631.
doi: 10.1186/s40064-015-1392-x. eCollection 2015.

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

Maureen Elizabeth Trudeau  1 , Judith-Anne W Chapman  2 , Baoqing Guo  3 , Mark J Clemons  4 , Rebecca A Dent  1 , Roberta A Jong  1 , Harriette J Kahn  1 , Kathleen I Pritchard  1 , Lei Han  2 , Patti O'Brien  2 , Lois E Shepherd  2 , Amadeo M Parissenti  3
Affiliations

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

Maureen Elizabeth Trudeau et al. Springerplus. .

Abstract

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.

Keywords: Docetaxel; Epirubicin; LABC; Microarray; Phase I/II; Response biomarkers.

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Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
a Schedule A maximum RIN by dose level and treatment time. b Schedule B maximum RIN by dose level and treatment time. c Schedule A and B maximum RIN by dose level and treatment time
Fig. 3
Fig. 3
a Schedule A heat map of patient gene expression data. b Schedule B heat map of patient gene expression data
See this image and copyright information in PMC

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