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Vinblastine-loaded platelets (VLP) have been successfully used in the treatment of idiopathic thrombocytopenic purpura. Three patients with platelet-phagocytizing tumors and thrombocytopenia were treated with VLP. Patient 1 has sustained a response for 11 months. Patient 2 was not evaluable for response because of early death. Patient 3 had a brief partial response. Vinblastine levels were measured by radioimmunoassay in the platelet-rich plasma, platelet-poor plasma, and serum. The pharmacokinetic data obtained on the patients suggest that: (a) the amount of vinblastine bound to platelets in vivo is a function of the platelet-poor plasma vinblastine level and the platelet count; (b) VLP will probably not have any therapeutic advantage, compared with iv vinblastine alone in patients with normal platelet counts; and (c) it appears that delivery of vinblastine was tumor-specific, since the bone marrow serum vinblastine level in patient 2, obtained when the marrow was replaced by tumor cells, was 2.5-fold higher than a simultaneous peripheral blood serum vinblastine level after VLP. Additional studies with VLP appear warranted in patients with platelet-phagocytizing tumors resulting in thrombocytopenia.

Cholorozotocin is a water-soluble chloroethylnitrosourea with the cytotoxic group attached to the C2 position of glucose. The distribution of the alkylating and carbamoylating moieties of the chlorozotocin molecule was determined in mice following the ip administration of an LD10 dose: 20 mg/kg. The half-life (T 0.5) for the plasma disappearance of intact drug was 5 minutes. The plasma disappearance of the ethyl-14C group was biphasic up to 120 minutes after administration; the T 0.5 of the initial phase was 17.5 minutes and the T 0.5 of the prolonged second phase was107 minutes. The disappearance of glucose-14C chlorozotocin followed kinetics similar to the chloroethyl-labeled compound. Fifteen minutes after administration, ethyl-14C drug concentrated maximally in the liver (194 nmols/g of tissue) and the kidney (131 nmols/g of tissue). Uptake into the bone marrow at 60 minutes after ip administration of the ethyl-labeled drug was 6.6 pmols of the ethyl-14C group covalently bound to proteins and nucleic acids per 10(7) nucleated cells. The concentration of ethyl-14C drug in the brain remained at 4 mnols/g of tissue up to 2 hours after administration, reflecting the water-soluble property of this new nitrosourea.