Capecitabine-induced Palmar-plantar Erythrodyesthesia

Case History

A 56-year-old lady was initially diagnosed with carcinoma of the breast in 1993. She underwent surgery, followed by adjuvant chemotherapy and radiotherapy. She was well until 1999, when she developed lung metastasis. Oral fluoropyrimidine monotherapy with capecitabine at 2510 mg/m²/day was given for 14 days every 3 weeks. She achieved a partial response after 3 treatment cycles, with no significant myelotoxicity. The main symptoms experienced during treatment included mild mucositis, generalised skin hyperpigmentation, a scaly rash over the tips of the fingers and toes, and lethargy; these symptoms became evident after the second chemotherapy cycle. The toxicity on her hands and feet accumulated and, after the 8 cycles of chemotherapy, she developed a tender erythematous swelling over her palms (figure 1) and plantar aspects of the feet (figure 2), with additional nail changes. The chemotherapy was discontinued after 10 cycles.

Hand-foot syndrome, or palmar-plantar erythrodyesthesia, is one of the most commonly reported toxicities of capecitabine use. The severity of the condition has been graded in table 1.¹

In the study reported by Blum et al., hand-foot syndrome occurred in 56% of patients who were treated with capecitabine, amongst whom 10% had severe disease (grade 3). Other adverse effects reported from the use of capecitabine included diarrhoea, nausea and vomiting, and fatigue.¹ In particular, hand-foot syndrome occurred.

Figure 1. Erythematous swelling over the palms.

Figure 2. Erythematous swelling over the plantar aspects of the feet.

  Table 1. Palmar-plantar erythrodyesthesia (hand-foot syndrome) grading scale.

Grade Clinical domain Functional domain     1 Numbness, dysaesthesia, paraesthesia, tingling, painless swelling, erythema Discomfort that does not disrupt normal activities     2 Painful erythema with swelling Discomfort that affects activities of daily living     3 Moist desquamation, ulceration, blistering, severe pain Severe discomfort Inability to work or perform activities of daily living

Reference

1. Blum JL, Jones SE, Buzdar AU, et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.

J Clin Oncol 1999;17:485-493.