Summary
A cytotoxic drug (vincristine, VC) was incorporated into low-density lipoprotein (LDL) and given to cancer patients for the first time by repeated intravenous injection. Individuals presenting with ovarian or endometrial cancer received four or five weekly doses of 1.4 mg/m2 LDL/VC. The uptake of LDL/VC by the adrenal cortex and the liver was minimised by concurrent administration of prednisolone and chenodeoxycholic acid. No febrile, allergic or other reaction attributable to the LDL occurred, and no side effect on haemopoietic, adrenal or liver functions was observed. The neurotoxic side effects commonly seen during VC therapy appeared to be reduced. These results suggest that directed cytotoxic therapy might be achieved in humans through the use of LDL as a carrier. Thus, dose-range and comparative studies using LDL/VC vs VCSO4 are warranted in malignancies in which treatment with the latter drug has been established.
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References
Budd D, Ginsberg H (1986) Hypocholesterolaemia and acute myelogenous leukaemia. Cancer 58:1361
Gal D, Ohashi M, MacDonald DC, Buchsbaum HJ, Simpson ER (1981) Low density lipoprotein as a potential vehicle for chemotherapeutic agents and radionuclides in the management of gynecologic neoplasms. Am J Obstet Gynecol 139:877
Hynds SA, Welsh J, Stewart JM, Jack A, Soukop M, McArdle CS, et al. (1984) Low-density lipoprotein metabolism in mice with soft tissue tumours. Biochim Biophys Acta 795:589
Jackson DV, Wells HB, Atkins JN, Zekan PJ, Whete DR, Richards F, Cruz JM, Muss HB (1988) Amelioration of vincristine neurotoxicity by glutamic acid. Am J Med 84:1016
Lapinjoki SP, Verajankorva HM, Huhtikangas AE, Lehtola TJ, Lounasmaa M (1986) An enzyme-linked immunosorbent assay for the antineoplastic agent vincristine. J Immunoassay 7:113
Legha SS (1986) Vincristine neurotoxicity: pathophysiology and management. Med Toxicol 1:421
Masquelier M, Vitols S, Peterson C (1986) Low-density lipoprotein as a carrier of antitumoral drugs: in vivo fate of drug-human low density lipoprotein complexes in mice. Cancer Res 46:3842
Masquelier M, Ros M, Peterson C, Rudling MJ, Vitols S (1989) Method for the production of a macromolecular carrier loaded with a biologically active substance Parent 4,868,158. United States Patent Office, Washington, D.C.
Rudling MJ, Collins VP, Peterson C (1983) Delivery of aclacinomycin A to human glioma cells in vitro by the low-density lipoprotein pathway. Cancer Res 43:4600
Shaw MJ, Shaw KV, Yanovich S, Iwanik M, Futch WS, Rosousky A, Schook LB (1987) Delivery of lipophilic drugs using lipoproteins. Ann NY Acad Sci 507:252
Shmulewitz A, Brook JG, Aviram M (1984) Native and modified low-density lipoprotein interactions with human platelets in normal and homozygous familial hypercholesterolaemic subjects. Biochem J 224:13
Smidt PC de, Berkel TJC van (1990) LDL-mediated drug targeting. Crit Rev Ther Drug Carrier Syst 7:99
Vallabhajosula S, Gilbert HS, Goldsmith SJ, Paidi M, Hanna MM, Ginsberg HN (1989) Low-density lipoprotein (LDL) distribution shown by99mTechnetium-LDL imaging in patients with myeloproliferative diseases. Ann Intern Med 110:208
Vitols S, Gahrton G, Öst Å, Peterson C (1984) Elevated low-density lipoprotein receptor activity in leukemic cells with monocytic differentiation. Blood 63:1186
Vitols S, Gahrton G, Peterson C (1984) Significance of the low-density lipoprotein (LDL) receptor pathway for the in vitro accumulation of AD 32 incorporated into LDL in normal and leukemic white blood cells. Cancer Treat Rep 68:515
Vitols S, Gahrton G, Björkholm M, Peterson C (1985) Hypocholesterolaemia in malignancy due to elevated low-density-lipoprotein-receptor activity in tumour cells: evidence from studies in patients with leukaemia. Lancet II:1150
Vitols SG, Masquelier M, Peterson C (1985) Selective uptake of a toxic lipophilic anthracycline derivative by the low-density lipoprotein receptor pathway in cultured fibroblasts. J Med Chem 28: 451
Vitols SG, Angelin H, Ericsson S, Gahrton G, Julinsson G, Masquelier M, Paul C, Peterson C, Rudling M, Soderberg-Reid K, Tidefelt U (1990) Uptake of low density lipoproteins by human leukemic cells in vivo; relation to plasma lipoprotein levels and possible relevance for selective chemotherapy. Proc Natl Acad Sci USA 87:2598
Vitols SG, Angelin B, Juliusson G, Gaston G, Paul C, Peterson C, Aberg B (1990) Elevated uptake of low-density-lipoprotein by malignant cells in patients with acute leukaemia and lung cancer. Proc Am Assoc Cancer Res 31:169
Vitols SG, Söderberg-Reid K, Masquelier M, Sjöström B, Peterson C (1990) Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex. Br J Cancer 62:724
WHO (1979) Handbook for reporting results of cancer treatment. Offset publication 48. WHO, Geneva
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Filipowska, D., Filipowski, T., Morelowska, B. et al. Treatment of cancer patients with a low-density-lipoprotein delivery vehicle containing a cytotoxic drug. Cancer Chemother. Pharmacol. 29, 396–400 (1992). https://doi.org/10.1007/BF00686010
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DOI: https://doi.org/10.1007/BF00686010