High dose chemotherapy for refractory urothelial carcinoma supported by peripheral blood stem cell transplantation

Abstract

Chemotherapy with methotrexate (MTX), vinblastine, doxorubicin, and cisplatin (M-VAC) is reported to be the most effective regimen for urothelial carcinoma. Complete response (CR) is observed in many cases. However, to the authors' knowledge there is no alternative therapy for nonresponders. Thus, the authors attempted high dose chemotherapy (HDC) supported with peripheral blood stem cells (PBSCs) collected after a modified method of mobilization to yield sufficient PBSCs for the HDC regimen employed.PBSCs were collected from ten patients, all of whom had recurrent and/or refractory transitional cell carcinoma. They were treated by modified M-VAC (with pirarubicin in place of doxorubicin) for PBSC harvest. Seven micrograms per kilogram of body weight of granulocyte-colony stimulating factor was injected subcutaneously daily from Day 10 of treatment to the end of the harvest. Harvest was initiated from the day when peripheral leukocyte counts exceeded 10,000/microL and usually continued for 3 consecutive days. Each patient received two courses of HDC. Therefore, 20 courses of HDC comprised of 300 mg/body of MTX, 1500 mg/m(2) of etoposide, and high dose carboplatin (CBDCA) were given to these 10 patients. The dose of CBDCA was determined by the formula of Calvert et al., in which the target area under the concentration versus time curve of CBDCA was adjusted to 21 mg. minute/mL.Sufficient PBSCs were collected for myeloablative chemotherapy in all patients. No patient responded to the treatment with modified M-VAC. Response to HDC was observed in nine of ten patients. CR was achieved in seven patients and a partial response was noted in two patients. A patient with multiple bone metastases showed no response. All patients rapidly recovered after PBSC transplantation. No patient died of treatment-related toxicity.HDC supported by PBSC transplantation was found to have a remarkable response against refractory urothelial carcinoma, for which there was no alternative therapy.