Metastatic extramammary Paget's disease successfully controlled with tumour dormancy therapy using docetaxel

SIR, Extramammary Paget’s disease (EMPD) is fatal once the tumour invades the dermis and metastasizes to the visceral organs. As no significantly effective treatment has yet been established, it is still extremely difficult to treat patients in the advanced stages of this disease. We report a patient with multiple bone and lung metastases of EMPD who was treated with weekly docetaxel. The patient was a 69-year-old man who had developed a large papillomatous tumour in the inguinal region and scrotum which was treated by wide local excision and bilateral groin lymph node dissection in April 2000. Histopathological examination showed the tumour cells to be those of EMPD. There was no recurrence or metastasis for about 4 years, but the patient began to suffer from lower back pain in January 2004. Computed tomography (CT) revealed multiple osteolytic lesions in the vertebrae and ilium with multiple nodules in the lungs, and the patient was admitted to Tsukuba University Hospital the following month for treatment. On admission, the symptoms were found to be derived from nerve root disturbance: severe lumbago, dysaesthesia in the toes, and lower limb paralysis. Magnetic resonance imaging (MRI) indicated not only multiple metastases in the vertebrae and ilium but also severe destruction of the 9th)11th thoracic vertebrae; the vertebral canal was almost completely surrounded by the tumour. Laboratory examination indicated elevated serum alkaline phosphatase and carcinoembryonic antigen (CEA, 65 ng dL). It is well known that CEA level correlates with tumour progression in advanced EMPD; nevertheless, as the patient had been surgically treated for EMPD 4 years earlier, the possibility that the metastatic disease arose from another primary site had to be excluded. Therefore, CT and MRI of the colon, rectum, stomach, pancreas and prostate, as well as tests for occult blood in the stool and prostate-specific antigen were performed. Based on the negative results of the examinations, we eventually diagnosed this case as metastatic EMPD. Radiotherapy of the lower thoracic vertebrae was administered at a dose of 3 Gy per day in five fractions per week (total dose 39 Gy). In addition, the patient received intravenous docetaxel therapy at a dose of 25 mg m weekly for 2 weeks, followed by a 1-week rest. To avoid allergic reaction, the patient was given dexamethasone 8 mg prior to docetaxel administration. The course of treatment is shown in Figure 1. A gradual improvement in the patient’s condition was accompanied by a decrease in the serum CEA level. Sclerotic changes were observed in metastatic lesions in the vertebrae, suggesting tumour regression and regeneration of the bone. Moreover, some of the metastatic lesions in the lung disappeared on CT scan (Fig. 2). Other than mild general fatigue, no toxicity due to chemotherapy was observed. The patient was discharged after the 10th course of therapy and is still receiving chemotherapy on an outpatient basis without serious side-effects. His clinical progress has been satisfactory, and currently, 6 months after discharge, he has little limitation in daily life at home. The prognosis of EMPD is extremely poor once the tumour metastasizes. As metastatic EMPD is relatively rare, there has been little progress in the development of systemic chemotherapy regimens for this disease. Some authors have reported tumour response with combination chemotherapy, e.g. 5fluorouracil (5-FU) + mitomycin C, carboplatin + 5-FU + leucovorin, and low-dose 5-FU + cisplatin therapy. However, these chemotherapy regimens require daily intravenous drips and may require a week’s hospitalization in some cases. In contrast, weekly docetaxel administration can be applied on an outpatient basis with a reduction of acute toxicity and only mild myelosuppression. Based on the recent results of clinical trials, doses of 36–42 mg m were recommended for the weekly schedule, and the objective response rate was reported to be up to 53% in metastatic breast cancer, 46% in prostate cancer, and 23% in nonsmall cell lung cancer. In this range Fig 1. Treatment and clinical outcome. CEA, carcinoembryonic antigen.