gms | German Medical Science

In the treatment of patients with life threatening or quality of life influencing diseases off-label-use of drugs is a ethical and medical challenge when no other treatments are available. With respect to the increasing costs in health care, also economical reasons may play a role in the off-label-use of drugs. An example: In 1974, lithium carbonate (Li₂CO₃) was approved by the American Food and Drug Administration (FDA) for the treatment and prophylaxis of manic-depressive patients in the USA. It had already been observed since 1950 that patients receiving lithium treatment exhibited an increase in the number of leukocyte cells in the peripheral blood.

To demonstrate the potential role of Li₂CO₃, approved as a drug for the treatment of manic-depressive patients as a potent proliferator for neutrophil granulocytes of patients with leukocytopenia to prevent febrile infectious diseases. The study's objective was to determine the effect of Li₂CO₃ on the proliferation of granulocytes, lymphocytes, and platelets after previous immunosuppressive therapy (chemo- or radiotherapy).

Out of a total of 540 cancer patients with chronic leukocytopenia who where treated with 400 mg Li₂CO₃ bid, 100 were selected at random to investigate the effect of Li₂CO₃ on haematopoiesis. Leukocytopenia was defined as leukocyte cell counts below 4,000 cells/µl for more than 6 months after chemo- or radiotherapy. The treatment group was compared for cell recovery from the time before, and at the end of treatment with Li₂CO₃ using a two-sided T-test for paired samples.

An increase of the mean cell count of leukocytes from 3,095±550 cells/µl [range 1,190 - 3,910] to 4,531±530 cells/µl [range 1,960 - 12,300 cells/µl] was observed at a treatment period between 5 and 10 days. The influence on lymphocyte recovery was statistically not significant. Platelet recovery was significant (p=0.003) for patients with low cell counts (<150,000 cells/µl) and increased from a mean of 124,851 cells/µl to 162,382 cells/µl. Patient tolerability to Li₂CO₃ therapy is very good.

Empirical observations may give some hints for complementary effects of approved drugs. Off-label-use of drugs should be possible for scientific progress in medicine in combination with well-designed observational studies, if safety aspects are considered and after informed consent. Off-label-use may lead to new indications of approved drugs and to treatments of patients with life threatening or rare diseases. Li₂CO₃ can be used to treat patients with chronic leukocytopenia following chemotherapy or radiotherapy extremely cost-effectively. Unfortunately this treatment has not won acceptance in clinical oncology in the face of highly cost-intensive treatment with recombinant CSF.