Cross-activity of various established antineoplastic regimens in primary breast cancer cells evaluated by the ex vivo ATP tumor chemosensitivity assay

Abstract

20086 Recently, various chemotherapy (Ctx) regimens are established in operable breast cancer (BC). Whereas anthracylines are now standard in high-risk patients (pts), the future role of taxanes or classical CMF is still controversial. Moreover, little is known which Ctx will be individually beneficial. This particular information is unlikely to be obtained from randomized trials because simultaneous treatment of one single pt with different competing protocols is inappropriate. Thus, we used ex vivo sensitivity profiles from native primary BC assessed with the ATP tumor chemosensitivity assay (ATP-TCA) to analyze the cross-activity of different standard regimens in individual pts. Each Ctx was tested at six different levels over 1.5 log range including both therapeutical and supra-therapeutical concentrations. Resistance, complete, and incomplete sensitivity were determined using a semiquantitative score. The following head-to-head comparisons of ex vivo activity were made: CMF, 4-OOH-cyclophosphamide (4-HC)+methotrexate (MTX)+5-Fluorouracil (5-FU) vs. EC, epirubicin (EPI)+4-HC, n = 56; CMF vs. paclitaxel (PCT), n = 34; CMF vs. docetaxel (DCT), n = 49; EC vs. PCT, n = 51; EC vs. DCT, n = 35; EC vs. EPI+PCT (ET), n = 45; PCT vs. DCT, n = 34. The ex vivo response rates were in good agreement with the expected clinical activity: CMF 52%, EC 63%, ET 85%, PCT 52%, DCT 49%. CMF and EC were equally active (=) in 68% BCs, CMF was superior (>) to EC in 16% and inferior (<) in 16%. The corresponding proportions (=/>/<) for the other comparisons were: CMF vs. PCT, 45%/31%/24%; CMF vs. DCT, 40%/40%/20%; EC vs. PCT, 49%/31%/20%; EC vs. DCT, 40%/40%/20%; EC vs. ET, 53%/ 9%/38%; PCT vs. DCT 55%/21%/24%. Generally, ET was the most active regimen, being equal or superior to EC in the majority of cases. However, CMF is clearly not inferior to EC or single agent taxanes. PCT and DCT are apparently not always the same. Facing the broad heterogeneity of chemosensitivity demonstrated in this study, we were able to show that the results of randomized trials cannot always be translated to an individual pt. Cross-activity analyses using the ATP-TCA may thus prove useful to allow for a more rational design of clinical trials in primary BC. [Table: see text]