Table 2

Efficacy of vinblastine-conjugate and its major metabolites in nude mice bearing PSA-producing and non-PSA-producing human tumor xenografts

A group of 10–12-week-old male nude mice were used for animal studies. On day 1, mice were inoculated s.c. in the left flank with the indicated cells. Later (24 h), the inoculated mice were started on the drug. Drugs were given i.p. once a day for 5 consecutive days. At the end of 5 and one-half weeks, blood was taken, and the tumors were excised. PSA and tumor weight values are expressed as a percentage of the value derived from vehicle-treated animals. LNCaP and CWR22 are PSA-producing tumors; Colo 320 is a non-PSA-producing tumor.

A.CompoundLNCaP tumor xenograft
% Tumor weight reduction (P)b
MTD (μmol/kg)Dose (μmol/kg)a% PSA reduction (P)b
dAc-Vin0.260.2614 (0.549)16 (0.595)
0.3925 (0.460)14 (0.686)
0.5270 (0.193)57 (0.272)
4-O-prolyl-dAc-Vin4.64.633 (0.400)60 (0.226)
5.819 (0.618)2 (0.996)
6.976 (0.093)67 (0.152)
4-O-(Ac-HypSSChgQSSP)-dAc-Vin21.41.243 (0.041)53 (0.073)
2.468 (0.054)54 (0.155)
4.983 (0.003)68 (0.020)
9.292 (0.001)77 (0.009)
15.399 (0.001)85 (0.005)
21.4100 (0.001)90 (0.005)
4-O-[Ac-HypSSChg(dQ)(dS)SP]-dAc-VinND12.3[54 increase (0.506)][64 increase (0.181)]
B.CompoundCWR 22 tumor xenograft
% Tumor weight reduction (P)b
MTD (μmol/kg)Dose (μmol/kg)a% PSA reduction (P)b
dAc-Vin0.260.26[14 increase (0.180)][19 increase (0.294)]
4-O-prolyl-dAc-Vin4.64.64 (0.718)9 (0.694)
4-O-(Ac-HypSSChgQSSP)-dAc-Vin21.412.299.7 (<0.001)89 (<0.001)
C.CompoundColo 320 tumor xenograft
% Tumor weight reduction (P)b
MTD (μmol/kg)Dose (μmol/kg)a% PSA reduction (P)b
dAc-Vin0.260.26NAc4 (0.880)
4-O-prolyl-dAc-Vin4.64.6NA[14 increase (0.705)]
4-O-(Ac-HypSSChgQSSP)-dAc-Vin21.412.2NA[21 increase (0.538)]
  • a Ten animals were treated at each dose.

  • b P > 0.05 indicates a nonsignificant result.

  • c NA, not applicable.