For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 170)
CAS No.:
Chem. Abstr. Name: Platinum, diamminedichloro-, (SP-4-2)-
A. Evidence for carcinogenicity to humans (inadequate)
No epidemiological study of cisplatin as a single agent was available to the Working Group. Occasional case reports of exposure to cisplatin, especially in the presence of concurrent therapy with other putative carcinogens, such as ionizing radiation, alkylating agents and other potent oncotherapeutic drugs, do not constitute evidence of carcinogenesis [ref: 1-3].
B. Evidence for carcinogenicity to animals (sufficient)
Multiple intraperitoneal administrations of cisplatin to mice significantly increased the incidence and number of lung adenomas. Similar treatments caused a significant increase in the incidence of skin papillomas in mice given promoting treatment of croton oil applied to the skin. The incidences of epidermoid carcinomas and of both malignant and benign tumours in internal organs were increased by the same treatment, but were not significantly different from those in controls [ref: 1,4]. In two studies, multiple intraperitoneal injections of cisplatin to rats induced leukaemia [ref: 5,6].
C. Other relevant data
In one study, cisplatin-adriamycin combination chemotherapy induced sister chromatid exchanges in peripheral blood lymphocytes of patients treated with this agent. In another study, antigenicity against cisplatin-DNA adducts was demonstrated in blood cells of treated patients [ref: 7].
Cisplatin induced structural chromosomal aberrations and sister chromatid exchanges in cells of rodents treated in vivo, but it did not induce dominant lethal mutations in mice. It transformed Syrian hamster embryo cells; it induced chromosomal aberrations, micronuclei and sister chromatid exchanges in both human and rodent cells in vitro, and mutation and DNA damage (including DNA cross-links) in rodent cells in vitro. In Drosophila, cisplatin induced aneuploidy and dominant lethal and sex-linked recessive lethal mutations. It induced chromosomal aberrations and mutation in plants. Cisplatin induced mutation, gene conversion and DNA damage in fungi and mutation and DNA damage in bacteria [ref: 7].
Overall evaluation
Cisplatin is probably carcinogenic to humans (Group 2A).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluation: Vol. 26 (1981)
References
1. IARC Monographs, 26, 151-164, 1981
2. Mead, G.M., Green, J.A., Macbeth, F.R., Williams, C.J., Whitehouse, J.M.A. & Buchanan, R. (1983) Second malignancy after cisplatin, vinblastin, and bleomycins (PVB) chemotherapy: a case report. Cancer Treat. Rep., 67, 410
3. Pedersen-Bjergaard, J., Rørth, M., Avnstrøm, S., Philip, P. & Hou-Jensen, K. (1985) Acute nonlymphocytic leukemia following treatment of testicular cancer and gastric cancer with combination chemotherapy not including alkylating agents: report of two cases. Am. J. Hematol., 18, 425-429
4. Leopold, W.R., Batzinger, R.P., Miller, E.C., Miller, J.A. & Earhart, R.H. (1981) Mutagenicity, tumorigenicity, and electrophilic complexes of 1,2-diaminocyclohexane. Cancer Res., 41, 4368-4377
5. Kempf, S.R. & Ivankovic, S. (1986) Chemotherapy-induced malignancies in rats after treatment with cisplatin as single agent and in combination: preliminary results. Oncology, 43, 187-191
6. Kempf, S.R. & Ivankovic, S. (1986) Carcinogenic effect of cisplatin(cis-diammine-dichloroplatinum(II), CDDP) in BD IX rats. J. Cancer Res. clin. Oncol., 111, 133-136
7. IARC Monographs, Suppl. 6, 178-181, 1987
Synonyms
See Also:
Toxicological Abbreviations
Cisplatin (PIM 132)
Cisplatin (UKPID)
Cisplatin (IARC Summary & Evaluation, Volume 26, 1981)