Gefitinib-Induced Severe Dermatological Adverse Reactions: A Case Report and Pharmacogenetic Profile

Abstract

Gefitinib is a selective inhibitor of the epidermal growth factor receptor that is used to treat advanced and metastatic non-small cell lung cancer (NSCLC). Dermatological adverse reactions are most commonly associated with gefitinib treatment. The cause of adverse reactions in individuals is multifactorial. Pharmacogenetics is an effective tool to detect such adverse reactions. This case report describes a female patient with NSCLC who was administered gefitinib at a dose of 250 mg/day. However, due to severe adverse dermatological reactions, the treatment was interrupted for 15 d and antibiotic therapy was administered to manage the skin rashes, maculopapular rashes, and hyperpigmentation. Treatment adherence was adequate, and no drug interactions were detected. A pharmacogenetic analysis revealed homozygosity in the ATP-binding cassette (ABC)-B1 rs1128503 (c.1236A>G), heterozygosity in ABCG2 rs2231142 (c.421G>T) and rs2622604 (c.-20+614T>C), and a non-functional variant of the cytochrome P450 family 3, subfamily A, member 5 (CYP3A5). The relationship between altered genetic variants and the presence of adverse reactions induced by gefitinib is still controversial. Overall, this case report highlights the importance of continuing to study pharmacogenetics as predictors of adverse drug reactions.

Keywords: ABCB1; adverse drug reaction; case report; cytochrome P450 enzyme system; gefitinib; pharmacogenetics; skin rash.

Figure 1

Adverse reactions induced by gefitinib (250 mg/day) in a 55-year-old woman. (a) Mild cutaneous adverse reactions on the face after 4 weeks of gefitinib treatment. (b) Severe cutaneous adverse reactions on the face after 10 weeks of gefitinib treatment. (c) Appearance of pustules and papules on the left side of the cheek after 10 weeks of gefitinib treatment. (d) Cutaneous adverse reactions on the face 7 d after interrupting gefitinib treatment and starting oral tetracycline (1 g twice daily) treatment. (e) Left side of the face 7 d after interrupting gefitinib treatment and starting oral tetracycline (1 g twice daily) treatment. (f) Right side of the face 7 d after interrupting gefitinib treatment and starting oral tetracycline (1 g twice daily) treatment. (g) Cutaneous adverse reactions on the face 15 d after interrupting gefitinib treatment and starting oral tetracycline treatment. (h) Left side of the face 15 d after interrupting gefitinib treatment and starting oral tetracycline treatment. (i) Right side of the face 15 d after interrupting gefitinib treatment and starting oral tetracycline treatment. (j) The face showed a serious adverse reaction 8 months after the re-introduction of gefitinib. (k) Patient abdomen exhibited mild adverse reactions 8 months after the re-introduction of gefitinib. (l) Right side of the costal region exhibited adverse reactions after the re-introduction of gefitinib. (m) Left side of the costal region exhibited adverse reactions after the re-introduction of gefitinib.