Capecitabine-induced radiation recall phenomenon: a case report

Introduction

We report a case of a radiation recall phenomenon after the administration of Capecitabine, consisting of pain, hyperpigmentation, and ulceration in the field of postmastectomy irradiation (which the patient received 3 years previously).

Case report

A 78-year old woman allergic to salicylics was diagnosed with a T4dN3M0 (American Joint Committee on Cancer) infiltrating ductal left breast carcinoma (inflammatory breast cancer) in March 2006. Owing to her general condition and advanced local disease, she was initially treated with primary hormonotherapy consisting of Letrozole 2.5 mg/d over a period of 6 months with a good local response as measured by ultrasound scanning. In October 2006, she was operated on and a modified radical mastectomy was performed. Pathology reported a 6 cm in diameter infiltrating ductal carcinoma pT4dN2a positive for both estrogen and progesterone receptors, and Her2-neu negative. After surgery she started on chemotherapy (Taxol 80 mg/m² on a weekly schedule for 4 weeks) and adjuvant radiotherapy (50 Gy over left hemithorax and supraclavicular nodes in February 2007). Immediately after initial radiotherapy, in 2007, she developed skin toxicity Radiation Therapy Oncology Group (RTOG) grade 2, which was successfully managed with topical medication (Radiocrem® Rotthafarm SL. 3 times a day). She started Letrozole 2.5 mg/d again in January 2007. In September 2009 she developed a neoplasic left pleural involvement and began hormonotherapy with Fulvestrant 500 mg/monthly for 5 months, followed by Exemestane 25 mg/d due to clinical and radiological progression. In May 2010, she developed new pleural progression, which was treated with Capecitabine at a dose of 1000 mg/m²/12h (3 cycles). Three months later in July 2010, she was noted to have developed a series of ulcers on the previous mastectomy scar, which had changed in colour (hyper and dispigmentation) and elasticity (stiffness and extreme fragility) over the skin of the previously irradiated area in the left hemithorax (Figure 1). A punch-biopsy was performed and carcinoma in the involved skin was ruled out. The diagnosis of a recall radiodermitis (ulcerating dermatitis, grade 4 RTOG) was thus established in July 2010 and so Capecitabine was withdrawn and palliative 20 mg Tamoxifen started. The skin began to improve after 3–4 weeks following withdrawal of Capecitabine and treatment with topical steroids (Menaderm® Menarini; Beclomeatsone 0.025%). She remains on Tamoxifen treatment, and the disease is now stable.

Figure 1. Recall dermatitis (RTOG grade 4): detail of ulcers.

Discussion

Radiation-recall dermatitis is an inflammatory reaction of the skin at the site of previous irradiation. Many chemotherapy drugs have been presumed to cause this phenomenon and a database to collect these rare reaction cases has even been proposed¹. It can also affect other anatomical areas such as the digestive system (when abdominal radiotherapy has been used)². Although a closer time gap is more usual, the time gap between the inflammatory reaction and previous radiation can range from days to several years³.

There are few reported cases of Capecitabine-induced radiation recall phenomenon, the first one being authored by Ortmann et al. in 2002⁴. Their hypothesis relied on the pro-drug entity of Capecitabine being capable of being activated in previously irradiated tissue.

More recently, Ghosal and Misra have reported a case⁵ with thoracic hyperpigmentation instead of inflammation being the main clinical finding. Other rare though well known Capecitabine side effects are hyperpigmentation associated with palmar-plantar erythrodisesthesia⁶ or even Stevens-Johnson syndrome⁷.

Conclusions

To our knowledge, this is the first reported case of Capecitabine-induced RTOG grade 4 (ulcerating dermatitis) recall skin toxicity of previously irradiated skin. We suggest it is relevant for differential diagnosis with other entities such as local cancer relapse or even surgical site infection. In case of any doubt such as in our case, punch biopsy can help. Clinicians should be aware of this phenomenon, even if a long period of time has lapsed since the previous radiation therapy.

Consent

Written informed consent for publication of the clinical details and clinical images was obtained from the patient.