International Agency for Research on Cancer (IARC) - Summaries & Evaluations
PROCARBAZINE HYDROCHLORIDE
VOL.: 26 (1981) (p. 311)
5. Summary of Data Reported and Evaluation
5.1 Experimental data
Procarbazine hydrochloride is carcinogenic in mice and rats after its
intraperitoneal administration, producing malignant tumours of the
nervous system, haematopoietic system and possibly other organs in
both species, and tumours of the mammary gland in rats only. Evidence
of carcinogenicity was also found in mice and rats following its oral
administration, in rats following its intravenous administration, and
in one instance following transplacental exposure. Two studies in two
species of nonhuman primates suggest that procarbazine hydrochloride
may also produce myelogenous leukaemia when administered by multiple
routes in the same animal.
Procarbazine hydrochloride can induce teratogenic effects in rats and
embryolethality at doses nontoxic to the mother. This compound is
mutagenic in bacteria, yeast, cultured mammalian cells and Drosophila
melanogaster, and in mice and rats in vivo.
5.2 Human data
Procarbazine hydrochloride is used primarily in the treatment of
Hodgkin's disease, non-Hodgkin's lymphoma and lung cancer, in
combination with other drugs.
The available data are insufficient to evaluate the teratogenicity,
mutagenicity or chromosomal effects of procarbazine hydrochloride in
humans.
Both case reports and epidemiological studies indicate that acute
nonlymphocytic leukaemia is produced in patients with Hodgkin's
disease treated with combined therapeutic regimens which include vinca
alkaloids, alkylating agents and procarbazine hydrochloride, often in
conjunction with radiotherapy. No data were available to the Working
Group which permit the assessment of the separate effects of
procarbazine hydrochloride.
5.3 Evaluation
There is sufficient evidence for the carcinogenicity of procarbazine
hydrochloride in mice and rats. There is limited evidence of its
carcinogenicity in monkeys. There is sufficient evidence for the
carcinogenicity in humans of intensive chemotherapeutic regimens that
include alkylating agents, vinca alkaloids, procarbazine hydrochloride
and prednisone. There is inadequate evidence of the carcinogenicity
of procarbazine hydrochloride alone in humans.
On the basis of the combined experimental and human evidence,
this compound should be considered for practical purposes as if it
presented a carcinogenic risk to humans.
For definition of the italicized terms, see Preamble Evaluation.
Subsequent evaluation: Suppl. 7 (1987)
Last updated: 8 April 1998