GLUTATHIONE CONCENTRATION MAY BE A USEFUL PREDICTOR OF RESPONSE TO 2ND-LINE CHEMOTHERAPY IN PATIENTS WITH OVARIAN-CANCER

BACKGROUND. No useful predictor of resistance or sensitivity to second -line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S- transferase-pi (GST-pi) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemot herapy. METHODS. Tumor samples were obtained from 26 patients with rel apsed epithelial ovarian cancer 3-4 weeks before the initiation of sec ond-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-pi in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concent ration was measured by an enzymatic assay. RESULTS. The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7 %) significantly exceeded that for the nonresponders (9.1%). Expressio n of GST-pi by immunohistochemical staining was more frequently observ ed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). W estern blot analysis detected GST-pi in all cases. There was no signif icant difference in the relative density values of the GST-pi Western blot analysis between the two groups. The mean value of GSH concentrat ion in nonresponders was significantly higher than in responders (18.4 +/- 9.7 vs. 7.5 +/- 8.2 mu g/mg protein). GSH concentration was below the cutoff point (10.3 mu g/mg protein) in all responders except one. CONCLUSIONS. Second-line chemotherapy consisting of etoposide and cis platin is effective in the treatment of relapsed epithelial ovarian ca ncer. In addition, tumor concentration of GSH may be a useful predicto r of the response to this therapy. (C) 1998 American Cancer Society.