Selective efficacy and safety of first-line and non-front-line antineoplastic agent combinations determined with individualized assays on colorectal cancer primary cultures

Purpose: To evaluate the efficacy of first-line and not-conventional antineoplastic drug combinations in colorectal adenocarcinoma primary cultures (CRAC-PCs). Methods: The efficacy and safety of 21 drug combinations (DCs) were evaluated using a simplified adenosine triphosphate-based chemotherapy response assay (sATP-CRA). The efficacy of each DC was reported as the percentage of cell death (PCD) produced on each of 12 CRAC-PCs, and the safety of each DC was evaluated as a safety window (SW). The SW was calculated as the quotient of PCD-CRAC-PC/PCD-hMSC-TA (human mesenchymal stem cells derived from adipose tissue). Nine DCs contained 5-fluorouracil and oxaliplatin, and 1-3 non-front-line drugs (NFLDs [carboplatin, doxorubicin, cisplatin, aspirin, or 3,3'-diindolylmethane]). The other 11 DCs only contained 2-4 NFLDs. Results: The efficacy and safety each DC were highly variable and depended on each CRAC-PC and DC. The usefulness of DCs was considered as a combination of PCD >20 and an SW >0.6: 13 /21 DCs (62%) met the requirements of efficacy and safety on 7/12 CRAC-PCs (58.3%). Conclusions: The resistance to 5-fluorouracil/oxaliplatin of CRAC-PCs and the usefulness of seven new DCs strongly suggest the convenience of performing ex vivo individualized assays to evaluate DCs and implement new and more useful treatments, instead of submitting patients to standardized chemotherapies in a blinded manner. Approaches such as this and properly evaluated in clinical assays could increase the life expectancy of patients with cancer and improve their quality of life.