Anticancer Agent-Induced Life-Threatening Skin Toxicities: A Database Study of Spontaneous Reporting Data

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening cutaneous and mucosal adverse reactions to drugs. Nevertheless, the connection to anticancer agents remains unclear. To provide insight into the association of such adverse reactions with anticancer agents, we analyzed the profile of anticancer agent-induced SJS and TEN in the Japanese population. Of the 9,738 SJS/TEN events recorded in a database of spontaneous reporting data, 485 (5%, further categorized as SJS, 384 events, 79%; TEN, 101 events, 21%) were identified as anticancer agent-induced, and 53 of these (11%) were fatal. Multivariate logistic regression analyses indicated that, compared with patients using other drugs, those using anticancer drugs had lower incident risk of death (hazard ratio [HR], 0.592; p = .0006), longer median time to onset of SJS/TEN (18 vs. 11 days; p < .0001; multivariate Cox regression: HR, 0.66; p < .0001), and a higher likelihood of developing SJS/TEN later than 70 days after initiation of the suspected causal agent (15% vs. 7%; p < .0001), highlighting the need for vigilance and continuous monitoring for SJS/TEN in patients treated with anticancer agents. IMPLICATIONS FOR PRACTICE: Life-threatening skin toxicities induced by anti-cancer agents indicated significantly lower incident risk of death and longer time to onset of symptoms than for those induced by other drugs.

Keywords: Cancer; Skin toxicity; Stevens‐Johnson syndrome; Toxic epidermal necrolysis; Treatment.

Figure 1.

Relationship between age and the prevalence of life‐threatening skin toxicities. The cohort included patients with Stevens‐Johnson syndrome or toxic epidermal necrolysis (n = 9,738). Age groups are defined in 10‐year bands or age of more than 80 years. The highest prevalence of drug‐induced skin toxicity was noted among patients aged 50–79 years, both among patients receiving anticancer agents and among those receiving non‐anticancer therapeutics. In this cohort of patients with drug‐induced life‐threatening skin toxicity, an anticancer agent was identified as the causative drug in 5.8%, 7.9%, and 7.8% of patients aged 50–59, 60–69, and 70–79 years, respectively, compared with only 3.4% and 2.0% of patients aged above 80 years or below 50 years, respectively.

Figure 2.

Time interval between first drug intake and onset of symptoms of skin toxicity. Data are provided for the overall cohort showing drug‐induced skin toxicity (A), as well as for the subcohort with SJS (B) and that with TEN (C). The cumulative incidence curve was obtained using Cox proportional‐hazards regression analysis. In each cohort, the anticancer agent group showed significantly longer time to onset than that noted in the non‐anticancer agent group. Abbreviations: HR, hazard ratio; SJS, Stevens‐Johnson syndrome; TEN, toxic epidermal necrolysis.

Figure 3.

Relationship between age and prevalence of death in patients with anticancer agent‐induced skin toxicity. Data are provided separately for SJS and TEN. Age groups are defined in 10‐year bands, with the last band covering patients aged above 80 years. The prevalence of death was higher among patients with TEN than among those with SJS for each age group (A). The death rate in patients aged above 80 years was significantly higher than that noted in those aged below 80 years, regardless of the type of skin toxicity (B). Abbreviations: SJS, Stevens‐Johnson syndrome; TEN, toxic epidermal necrolysis.