INDIVIDUALIZED CHEMOTHERAPY FOR PATIENTS WITH NONSMALL CELL LUNG-CANCER DETERMINED BY PROSPECTIVE IDENTIFICATION OF NEUROENDOCRINE MARKERS AND IN-VITRO DRUG-SENSITIVITY TESTING

We attempted to prospectively select individualized chemotherapy for 1 65 non-small cell lung cancer patients based on in vitro analysis of n euroendocrine (NE) markers and drug sensitivity testing (DST) using fr esh tumor. The chemotherapy used for small cell lung cancer (SCLC) was selected when NE marker expression determined by L-dopa decarboxylase assay was documented. Selection of chemotherapy for other patients wa s guided by DST results using a modified dye exclusion assay when avai lable; otherwise etoposide and cisplatin was administered. A total of 112 of 165 (68%) specimens were assayed for L-dopa decarboxylase and 3 6 patients (22%) had DST. In vitro data directed management for 27 of 96 (28%) patients given chemotherapy: 6 with NE markers were treated w ith the SCLC regimen; and 21 (58% of those with DST) received their DS T-selected chemotherapy regimen. There were no significant differences in response rate among all 3 treatment arms (P = 0.076). However, res ponse to chemotherapy for the patients treated prospectively with a SC LC regimen was 3 of 6 (50%), marginally better than patients given the ir DST-selected chemotherapy regimen (2 of 21; 9 %; P = 0.056) or thos e treated with etoposide and cisplatin (10 of 69; 14%; P = 0.061). Whe n patients whose NE markers were identified retrospectively are includ ed, 4 of 9 (44%) responded to administered chemotherapy, compared to 7 of 55 (13%) with no NE markers present (P = 0.04). There were no diff erences in survival among the three treatment groups. Cisplatin and et oposide comprised the most active regimen in vitro for tumors from 16 of 36 (44%) patients, potentially limiting the benefit of DST since th is is often the empiric therapy for non-SCLC. Furthermore, the correla tion between in vitro and clinical response is nonsignificant for all drugs tested, highlighting the overall relative resistance of non-SCLC tumors to currently available chemotherapy.