Presant, Cary A.

e18538 Background: The drug-induced apoptosis MiCK assay has been predictive of outcomes in acute myelocytic leukemia, ovarian cancer, and a variety of solid tumors including breast cancer (Cancer Research 2012; 72:3901). We compared MiCK assay results in mesothelioma patients (pts) with NSCLC pts. Methods: Specimens from tissue or effusions were submitted to a central lab, processed to purify neoplastic cells, and a MiCK assay was performed as described (Cancer 2012; 118: 4877). Best chemotherapy regimens are defined as drugs/combinations with highest kinetic units (KU) of apoptosis +/- 1 SD compared to other drugs (this definition was predictive of outcomes in ovarian cancer). Active drugs have results over 1.0 KU of apoptosis. Results: 10 specimens have been submitted and 7 have been successful. Mean age was 69 and mean number of prior lines of therapy were 0.7 in 3 mesothelioma pts and 2.0 in 4 NSCLC pts. Mean number of drugs or combinations assayed successfully were 41 in mesothelioma and 20 in NSCLC. In mesothelioma, best active chemotherapy regimens (>1.0 KU) have been pemetrexed+doxorubicin, epirubicin, idarubicin, cyclophosphamide, ifosfamide, and dactinomycin. In NSCLC, best active regimens have been doxorubicin+cisplatin, irinotecan, and cyclophosphamide+doxorubicin+vincristine. In mesothelioma pts, the assay has been able to identify unexpected significant activity of several drugs: epirubicin, idarubicin, daunorubicin, dactinomycin, bendamustine, melphalan, vincristine, topotecan, azacytidine and bortezomib. Conclusions: Use of the MiCK assay in mesothelioma is at least as successful in the laboratory as it is in NSCLC. Unexpected new leads for innovative therapeutic strategies have been identified by the in vitro results. This feasibility study justifies a prospective controlled trial of the MiCK assay in mesothelioma and NSCLC pts. Clinical trials of drugs with unexpected activity are warranted in mesothelioma pts. Clinical trial information: NCT 01770665.

Abstract A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development. Cancer Res; 72(16); 3901–5. ©2012 AACR.