A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-FINDING STUDY OF ORG-2766 IN THE PREVENTION OR DELAY OF CISPLATIN-INDUCEDNEUROPATHIES IN WOMEN WITH OVARIAN-CANCER

Objective. The objective was to evaluate the efficacy of Org 2766 (a h exapeptide analogue of ACTH) in the prevention or delay of cisplatin-i nduced neuropathy during chemotherapy in women with ovarian cancer as measured by vibration perception threshold (VPT). Methods. In this ran domized, multicenter, double-blind, placebo-controlled study, 196 wome n with ovarian cancer were treated with cisplatin 75-100 mg/m(2), cycl ophosphamide 600-1000 mg/m(2) plus placebo or two dose levels of Org 2 766. The cisplatin-induced neuropathies were monitored by determining the VPT with the Vibratron II, VPT was determined for both the most se nsitive great toe and the Index finger on a monthly basis during treat ment and months 1, 2, and 3 postchemotherapy, Once the blind was broke n, it was found that 174 women (59 in placebo, 58 in 2 mg, and 57 in 4 mg) had enough data to allow evaluation, Results. Over the course of follow-up, the VPT was found to increase, This is consistent with the development of cisplatin-induced peripheral neuropathies. The baseline VPT for the index finger was less than that of the great toe (0.55 vs 2.13), but the percentage change in VPT was the same for both (percen tage increase in VPT of about 350%). When the VPTs are compared accord ing to the dose of Org 2766 given, there appears to be no difference i n the rate of change or degree of neuropathies that developed in these women receiving cisplatin and cyclophosphamide. Conclusions. The deve lopment of cisplatin-induced neuropathies is confirmed by measurement of the VPT, The rate of development of neuropathies seems to accelerat e after the sixth course of cisplatin, When the development of neuropa thies is evaluated on the basis of Org 2766 dosage, it is found that t here Is no difference in the rate or degree of neuropathies seen, Inst ead of providing protection from and delay of onset of peripheral neur opathies caused by cisplatin, these results suggest that the administr ation of Org 2766 appears to cause an increase in the rate of change a nd degree of neuropathies (P > 0.05). (C) 1997 Academic Press.