Neurotoxicity of purine analogs: a review.
OBJECTIVE
The purine analogs, fludarabine, cladribine, and pentostatin, are active against a broad spectrum of indolent lymphoid malignancies. They also have similar toxicities, including myelosuppression, immunosuppression, and sporadic neurotoxicity. This review compares the spectrum of neurotoxicity of each of these agents. Now that these drugs are commercially available and are being widely used, physicians should be aware of potentially serious side effects that may be encountered.


METHODS
The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the fall of 1993. In addition, case records from National Cancer Institute (NCI) Group C protocols were reviewed for fludarabine in chronic lymphocytic leukemia (CLL), and cladribine and pentostatin in hairy cell leukemia (HCL), as well as adverse drug reactions reported to the NCI from January 1980 through September 1993.


RESULTS
At higher than recommended doses, life-threatening and fatal neurotoxicity were encountered with all three drugs. At the recommended doses, each agent induced neurotoxicity in approximately 15% of patients, mostly mild and reversible. However, severe neurologic complications were reported; these were occasionally delayed, sometimes fatal, but often at least partially reversible.


CONCLUSIONS
The doses of these three agents should not be increased above the recommended levels. Development of moderate or worse neurotoxicity should result in discontinuation of that drug.
Cheson
B D
BD
Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Vena
D A
DA
Foss
F M
FM
Sorensen
J M
JM
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D017338:Cladribine / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced; D015649:Pentostatin / Q000009:adverse effects; D011684:Purine Nucleosides / Q000009:adverse effects*; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D011684:Purine Nucleosides; D015649:Pentostatin; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine