Table 6

Exploratory toxicity study in LNCaP tumor-bearing nude mice

An exploratory efficacy study was conducted to compare the vinblastine-conjugate with desacetyl-vinblastine. The vinblastine-conjugate and desacetyl-vinblastine were tested at their MTDs of 21.4 and 0.26 μmol/kg, respectively. These dosages were given as single i.p. injections once a day for 5 consecutive days to adult male nude mice that had been inoculated s.c. with 17 million LNCaP cells before treatment. Animals were necropsied 4 weeks after the last drug dose. Histological effects were observed only in the tissues indicated below. Grade: 0, none; 1, very slight; 2, slight; 3, moderate; 4, marked; 5, severe.

Animal no.Terminal body weight (grams)Tumor weight (grams)Serum PSA (μg/ml)Tumor cellularity (grade)Testicular degeneration (grade)Myelopathy (grade)Neuropathy (grade)
Control vehicle127.10.98127.664100
226.41.01154.864100
326.950.79213.975200
429.21.26216.964000
526.21.87204.365100
Average27.171.18183.564.4100
Desacetyl-vinblastine (0.26 μmol/kg)630.30.79205.964000
727.40.5886.244000
827.10.91175.64000
931.21.92319.974000
10280.9682.094000
Average28.81.03173.974000
Vinblastine-conjugate (21.4 μmol/kg)1128.180.0901401
1229.250.101412
1329.190.101312
1428.290.141.532501
1527.880.0801512
Average28.560.10.311.24.20.61.6