Canadian Cancer Trials Group Bulletins

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Canadian Cancer Trials Group MA.22 - A Phase I/II Study of Increasing Doses of Epirubicin and Docetaxel Plus Pegfilgrastim for Locally Advanced Or Inflammatory Breast Cancer

Primary results of Canadian Cancer Trials Group MA.22 were recently published online in SpringerPlus.

Canadian Cancer Trials Group MA.22 was a non-randomized phase I/II clinical trial to determine optimal dosing regimens for docetaxel/epirubicin combination chemotherapy in women with locally advanced or inflammatory breast cancer.

The primary objective of the phase I portion of each schedule was to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), and the dose for the q3 weekly and q2 weekly regimens. Phase I secondary objectives were to conduct microarray and immunohistochemical assessments of biomarker sensitivity/resistance to epirubicin and docetaxel.

The primary objective of phase II for both schedules was to evaluate clinical response rates at selected dose levels. Clinical response was defined as complete clinical response (absence of disease by palpation post-treatment) or partial response (patients with caliper measurements exhibiting a decrease in tumor volume ≥50 %). Patients with tumor volume decreases <50 % were considered to have stable disease. If tumors increased in size, then patients had progressive disease.

In phase II, secondary objectives were to examine pathologic complete response rates (pCR) (pathologic absence of tumor in the breast and axillary lymph nodes at primary surgery), duration of response (time from CR or PR until progression), toxicities by NCI Common Toxicity Criteria V2.0, biomarker assessments of response to therapy, and time to distant metastasis (defined as time from registration to the first evidence of recurrent disease) and survival (time to death). The pCR rate was too low for pCR to be used as an endpoint for biomarker assessments so clinical response was used.

The authors concluded that epirubicin/docetaxel combination chemotherapy can be delivered in locally-advanced breast cancer (LABC) patients with acceptable toxicity. This regimen can, in some patients, induce strong reductions in tumor RNA integrity that are associated with post-treatment pCRs. Elevated expression of specific genes within 17q12 near the HER2/ERBB2 locus (and other genes) were found to be associated with a complete clinical response to epirubicin/docetaxel chemotherapy. These genes could represent new targets for drug development that could improve clinical response to future regimens.

Trudeau M, Chapman JA, Guo B, Clemons M, Dent R, Jong R, Kahn H, Pritchard K, Han L, O'Brien P, Shepherd L, Parissenti A. A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: Canadian Cancer Trials Group MA.22 (ONLINE). SpringerPlus 4: 631, 2015.

http://www.springerplus.com/content/4/1/631