169 P - Glutatiflon (GSH) for protection of cisplatinum (CDDP) induced neuro- and nephrotoxicity

Abstract

CDDP is a widely used antitumor agent effective in the treatment of solid tumors. Efforts to improve the response rates in advanced disease by escalating the dose have been limited by unacceptahle toxicity. Based on experimental and clinical studies indicating that reduced GSH is a protective agent against CDDP-induced neuro-, oto-, and nephrotoxicity, a raodomized clinical trial with high dose CDDP including GSH (Group A) or intensive hydration (Group B) was designed for patients with advanced Non small cell lung cancer (NSCLC) or Squamous-cell-carcinomas of the head, and neck (SCC). To date, a total of 21 patients (pls)(l8 males, 3 females) with a median age of 54 years (range 35–74) entered this study (NSCLC:n=5;SCC: n=16; all stage III and IV). All pts received 80 mg/m’ CDDP + YP·16 or 5-FU every 4 weeks for a minimum of 3 cycles. PIs in group A (n=ll) received 5 g of GSH before CDDP therapy and 2000ml of normal saline. The control group B (n=10) received 4000m1 of normal saline and forced diuresis only. A median of 5 cycles (range 1-10) has been given to these pts (median observation time: 17 months, range 529). 15/21 pts were currently evaluable for response (4pts early deaths, 2 withdrawals). The overall response rate was 14/15 (93%) pts (CR: 2/14=14%, PR 6/14=43%, SD 6/14=43%). The response rate in group A was 8/9 (89%) pts (CR 2/8=25%, PR 2/8=25%, SD 4/8=50%). In group B the overall response rate was 6/6 (100%) pts (CR 0/6: PR 4/6=67%, SD 2/6=33%). 16 pts were evaluable for myelotoxicity, nephrotoxicity and neurotoxicity: We observed in 3/9 (33%) pts of group A and in 5/7 (70%) pts of group B severe neutropenia (WHO grade IV only in group B). Nephrotoxicity was noticed in 1/16 (6%) pts (group B). Ototoxicity and neurotoxicity, evaluable in 10/20 pts, were mild and comperable between the two groups. This preliminary data shows, that GSH might be a protectic agent against CDDP-induced toxicities, with allows the reduction of hydration therapy and forced diuresis, without reducing anti-tumor activity of the cytotoxic agent.