Vindesine (VDS; deacetyl vinblastine amide sulfate) given i.p. daily completely inhibited the growth of both the Ridgeway osteogenic sarcoma at 0.4 mg/kg and the Gardner lymphosarcoma at 0.25 mg/kg. In contrast, the parent alkaloid, vinblastine (VLB), at 0.5 mg/kg was inactive against these two tumors. VDS caused inhibition of growth of the Mecca lymphosarcoma that was comparable to the inhibition by vincristine (VCR), (60 versus 68%) while VLB caused 41% inhibition. The Ca115 Shionogi mammary carcinoma did not respond to VDS, but both VLB and VCR caused inhibitions of 62 and 67%, respectively. The Ca755 mammary adenocarcinoma showed a moderate response to VDS (46%) and VCR (39%), and no response to VLB. The Sarcoma 180 ascites tumor (solid, s.c.), the X5563 myeloma, and the C3H mammary carcinoma were not responsive to VDS, VLB, or VCR.

VDS caused a 113% prolongation of life in mice with the B16 melanoma (i.p.), and there were three of ten 45-day survivors in one study, and ten of ten 45-day survivors in another study. VLB had two of ten and eight of ten 45-day survivors in the same studies. Animals inoculated with the P388 leukemia and the Walker 256 and Ehrlich ascites tumors had greater than 100% prolongation of life with many indefinite survivors when treated with VDS, VLB, or VCR. The L1210, AKR, L5178Y, and C1498 leukemias showed no response to VDS given daily at 1.0 mg/kg.

In tissue cultures of Chinese hamster ovary cells, the minimum effective concentration of VDS that caused 10 to 15% accumulation of cells in mitosis was 2.3 × 10-9m, for VLB it was 2.2 × 10-8m, and for VCR it was 7.3 × 10-9m. The concentration of VDS needed for 40 to 50% accumulation of cells in mitosis was 2.8 × 10-8m; for VLB it was 8.3 × 10-8m; and for VCR it was 2.4 × 10-8m.

1

Presented in part at the 69th Annual Meeting of the American Association of Cancer Research, March 27 to 29, 1974, Houston, Texas (17).

This content is only available via PDF.