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

BACKGROUND, Chemotherapy with methotrexate (MTX), vinblastine, doxorubicin, and cisplatin (M-VAC) is reported to be the most effective regimen for uro thelial carcinoma. Complete response (CR) is observed in many cases. Howeve r, to the authors' knowledge there is no alternative therapy for nonrespond ers. Thus, the authors attempted high dose chemotherapy (HDC) supported wit h peripheral blood stem cells (PBSCs) collected after a modified method of mobilization to yield sufficient PBSCs for the HDC regimen employed. METHODS, PBSCs were collected from ten patients, all of whom had recurrent and/or refractory transitional cell carcinoma. They were treated by modifie d M-VAC (with pirarubicin in place of doxorubicin) for PBSC harvest. Seven micrograms per kilogram of body weight of granulocyte-colony stimulating fa ctor was injected subcutaneously daily from Day 10 of treatment to the end of the harvest. Harvest was initiated from the day when peripheral leukocyt e counts exceeded 10,000/mu L and usually continued for 3 consecutive days. Each patient received two courses of HDC. Therefore, 20 courses of HDC com prised of 300 mg/body of MTX, 1500 mg/m(2) of etoposide, and high dose carb oplatin (CBDCA) were given to these 10 patients. The dose of CBDCA was dete rmined 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 . RESULTS. Sufficient PBSCs were collected for myeloablative chemotherapy in all patients. No patient responded to the treatment with modified M-VAC. Re sponse to HDC was observed in nine of ten patients. CR was achieved in seve n patients and a partial response was noted in two patients. A patient with multiple bone metastases showed no response. All patients rapidly recovere d after PBSC transplantation. No patient died of treatment-related toxicity . CONCLUSIONS. HDC,supported by PBSC transplantation was found to have a rema rkable response against refractory urothelial carcinoma, for which there wa s no alternative therapy. (C) 1999 American Cnncer Society.