Sudden death in cancer patients receiving lithium.

Abstract

Lithium carbonate may attenuate the incidence and severity of infection associated with cancer chemotherapy but does not appear to improve patient survival. Of 100 patients with small-cell lung cancer receiving an identical regimen of cyclophosphamide, doxorubicin, and vincristine, 40 were assigned to treatment with lithium concurrently. To date, 60 patients have died, including 14 who died suddenly of apparent cardiovascular causes without evident progression of neoplastic disease or concurrent illness. Thirteen of the 14 sudden deaths were among 50 patients with clinical or electrocardiographic evidence of cardiovascular abnormalities before study entry. Among patients with pretreatment cardiovascular abnormalities, lithium administration was associated with a greater risk of sudden death and shorter survival. A strong interaction for risk of death was evident between lithium treatment and the use of bronchodilators. In multivariate analysis, the major predictors of patient survival were the quality of tumor response and treatment with lithium with or without bronchodilators. Lithium treatment is a major risk factor for sudden death in cancer patients with pretreatment cardiovascular changes receiving combination chemotherapy including an anthracycline antibiotic.

Lithium: evidence reconsidered

“…The clinical significance of these changes has been ques tioned and some reviewers have concluded that they are unlikely to lead to severe renal failure (Hwang & Tuason, 1980), although it is probable that vulnerability to lithium toxicity and other renal insults is increased. Lithium may cause cardiac conduction defects, most commonly sinus node dysfunc tion (Mitchell & Mackenzie, 1982), and it has been associated with sudden death in people with pre-existing cardiovascular ab normalities or risk factors such as a family history of cardiovascular disease (Shopsin et a!, 1979;Lyman et a!, 1984). It is also a well-known teratogen which causes cardiac abnormalities and an increased risk of Ebstein's anomaly (Cohen et a!, 1994).…”

Lithium‐stimulated proliferation and alteration of phosphoinositide metabolites in MCF‐7 human breast cancer cells

“…If lithium were to stimulate the growth of hormonedependent breast tumors in situ, as it does tumor cells in tissue culture, then lithium therapy for bipolar disorder in conjunction with tamoxifen anticancer therapy might be associated with shorter time to recurrence of the cancer and more rapid growth of recurring tumors. Comparison of mortality rates alone would be complicated by the increase in frequency of sudden cardiovascular death that has been reported with lithium treatment (Lyman et al, 1984). The growth of MCF-7 or ZR-75 cell tumors in athymic mice could provide an effective model to assess the effect of lithium on tumor development (animal models described in Jordan and Murphy, 1990).…”

Cancer risk from inorganics

“…Several reports have suggested that lithium therapy does not contribute to the longevity of the patient [252,253]. The mechanism of lithium induced leukocytosis is thought to involve a direct stimulation of granulocyte production [249].…”

“…neurotoxicity [258], thyroid function effects [259] sinus node dysfunction [260], and sudden death [253].…”

“…Since some uncertainty exists about the efficacy of adjunct lithium treatment in chemotherapy [252,253], perhaps it should be viewed with caution.…”