The effect of diethyldithiocarbamate on the haematological toxicity and antitumour activity of carboplatin. 1987

S E Dible, and Z H Siddik, and F E Boxall, and K R Harrap
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, U.K.

Carboplatin has recently been established as an effective agent in cancer chemotherapy. The dose limiting toxicity of this platinum complex is myelosuppression and, in this study, we have shown that through the use of diethyldithiocarbamate (DDTC), a protective thiol compound, the toxicity in rodents can be ameliorated and lethality prevented. DDTC protected against carboplatin-induced leucopoenia and anaemia when administered as a single bolus or as a multiple schedule incorporating three injections. With the single bolus, the effectiveness of this protection decreased as the lag time between carboplatin and DDTC administrations increased. Thrombocytopoenia was unaffected by DDTC. The growth profile of ADJ/PC6A tumour in mice was dependent on the timing of DDTC administration when given in combination with the platinum complex. The tumour growth delay, however, was unaffected by DDTC at any schedule. Multiple injections of DDTC increased the ED90 for carboplatin from 5.0 to 7.5 mg/kg. The LD50 value was increased from 115 to 216 mg/kg with the same DDTC schedule. Thus, DDTC improved the therapeutic index of carboplatin by 25%. A clinical role for the use of DDTC as a protective agent for carboplatin-induced toxicities is suggested.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D009944 Organoplatinum Compounds Organic compounds which contain platinum as an integral part of the molecule. Compounds, Organoplatinum
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004050 Ditiocarb A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM. Diethyldithiocarbamate,Diethylcarbamodithioic Acid,Diethyldithiocarbamic Acid,Dithiocarb,Ditiocarb Sodium,Ditiocarb, Ammonium Salt,Ditiocarb, Bismuth Salt,Ditiocarb, Lead Salt,Ditiocarb, Potassium Salt,Ditiocarb, Sodium Salt,Ditiocarb, Sodium Salt, Trihydrate,Ditiocarb, Tin(4+) Salt,Ditiocarb, Zinc Salt,Imuthiol,Sodium Diethyldithiocarbamate,Thiocarb,Zinc Diethyldithiocarbamate,Ammonium Salt Ditiocarb,Bismuth Salt Ditiocarb,Diethyldithiocarbamate, Sodium,Diethyldithiocarbamate, Zinc,Lead Salt Ditiocarb,Potassium Salt Ditiocarb,Sodium Salt Ditiocarb,Sodium, Ditiocarb,Zinc Salt Ditiocarb
D005260 Female Females
D006400 Hematocrit The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value. Erythrocyte Volume, Packed,Packed Red-Cell Volume,Erythrocyte Volumes, Packed,Hematocrits,Packed Erythrocyte Volume,Packed Erythrocyte Volumes,Packed Red Cell Volume,Packed Red-Cell Volumes,Red-Cell Volume, Packed,Red-Cell Volumes, Packed,Volume, Packed Erythrocyte,Volume, Packed Red-Cell,Volumes, Packed Erythrocyte,Volumes, Packed Red-Cell
D000740 Anemia A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN. Anemias

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