Capecitabine is rarely used as part of systemic chemotherapy in head and neck squamous cell carcinoma but it is more commonly used in breast, esophageal, gastric, colorectal, and pancreatic cancers [
7‐
11]. On the other hand, capecitabine is one of the most commonly prescribed regimes for recurrent and metastatic NPC, a separate disease entity from head and neck squamous cell carcinoma based on its different etiology and geographical epidemiology, since the response rate ranges from 23.5 % as monotherapy to 62.5 % when used in combination with cisplatin [
12‐
15]. More recently, capecitabine has also been found efficacious as induction chemotherapy followed by concurrent chemoradiation in a phase III randomized controlled trial conducted in Hong Kong [
16]. Radiation recall related to prior use of capecitabine has been reported in patients with breast and pancreatic cancers [
20‐
22]. However, it has not been reported so far in head and neck cancers, including NPC. The exact pathophysiology for radiation recall phenomenon remains to be deciphered. Vascular damage, epithelial stem cell sensitivity or hypersensitivity to chemotherapeutic agents have been postulated as the underlying mechanisms [
5,
23]. More recently, thymidine phosphorylase, a potent angiogenic factor was shown to be associated with the development of radiation recall after capecitabine use [
22,
24]. Sawada
et al. revealed that external radiotherapy induces thymidine phosphorylase and it enhanced the efficacy of capecitabine in human cancer xenografts [
25]. Thymidine phosphorylase produces 2-deoxy-D-ribose-1-phosphate during thymidine catabolism, which in turn generates oxygen radical species during the early stages of protein glycation. It was suggested that thymidine led to oxidative stress in thymidine phosphorylase-overexpressing cancer cells, leading to production of stress-induced angiogenic factors, vascular endothelial growth factor, and interleukin-8 and induced matrix metalloproteinase 1, accounting for thymidine phosphorylase-induced angiogenesis [
22,
25]. Upregulation of thymidine phosphorylase by previous external radiotherapy gave rise to development of angiogenesis in the previously irradiated region, leading to hypervascularity and erythema. In fact, the well-recognized palmar-plantar erythrodysethesia (hand-foot syndrome) as a common side effect of capecitabine, may be due to this hypervascularity sequela. Since our patient had received capecitabine continuously for more than 1 year, the accumulative dose of capecitabine might predispose to the development and persistence of her radiation recall. Treatment for radiation recall is most largely conservative with close surveillance. The subsequent irreversible damage of the underlying dermis brought about by prolonged exposure to capecitabine may explain her poor response to symptomatic treatment. Medication like moisturizers, antihistamines or emollients may alleviate symptoms of desquamation, itchiness or warmth. Topical or systemic glucocorticoids may help reduce the inflammatory response but they are usually not curative. Laser therapy, as our patient received as per self-intention, was not proven effective in alleviating the skin condition. Response rates to these symptomatic treatment have been poorly understood as they heavily depend on the pharmacokinetics of the causative agent, duration of use of the causative agent, and whether irreversible skin damage has occurred or not [
2,
5]. Usually the recall reaction may resolve more rapidly after discontinuation of intravenous agents rather than oral treatment. Some reactions to intravenous agents may improve within hours. However, it may takes weeks, months or even longer for the recall reaction to resolve, especially if the causative agent is an oral medication [
2].