A randomized, multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer

Abstract

Objective: The objective was to evaluate the efficacy of Org 2766 (a hexapeptide analogue of ACTH) in the prevention or delay of cisplatin-induced neuropathy during chemotherapy in women with ovarian cancer as measured by vibration perception threshold (VPT).

Methods: In this randomized, multicenter, double-blind, placebo-controlled study, 196 women with ovarian cancer were treated with cisplatin 75-100 mg/m2, cyclophosphamide 600-1000 mg/m2 plus placebo or two dose levels of Org 2766. The cisplatin-induced neuropathies were monitored by determining the VPT with the Vibratron II. VPT was determined for both the most sensitive great toe and the index finger on a monthly basis during treatment and months 1, 2, and 3 postchemotherapy. Once the blind was broken, 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 (0.65 vs 2.13), but the percentage change in VPT was the same for both (percentage increase in VPT of about 350%). When the VPTs are compared according to the dose of Org 2766 given, there appears to be no difference in the rate of change or degree of neuropathies that developed in these women receiving cisplatin and cyclophosphamide.

Conclusions: The development of cisplatin-induced neuropathies is confirmed by measurement of the VPT. The rate of development of neuropathies seems to accelerate after the sixth course of cisplatin. When the development of neuropathies is evaluated on the basis of Org 2766 dosage, it is found that there is no difference in the rate or degree of neuropathies seen. Instead of providing protection from and delay of onset of peripheral neuropathies caused by cisplatin, these results suggest that the administration of Org 2766 appears to cause an increase in the rate of change and degree of neuropathies (P > 0.05).