Hitoshi Kadena

Neoadjuvant Chemotherapy for Locally Advanced Urothelial Cancer of the Upper Urinary Tract

Cisplatin-based multiple-drug chemotherapy is currently considered the most effective treatment for advanced and metastatic urothelial cancers. We treated 15 patients with locally advanced urothelial cancers of the upper urinary tract using the cisplatin-based multiple-drug regimen in a neoadjuvant setting. The regimens administered were: M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin); MEC (methotrexate, etoposide and cisplatin), or M-VEC (methotrexate, vinblastine, epirubicin and cisplatin). Total nephroureterectomy was performed in all patients and response was evaluated pathologically Of 15 patients 2 (13%) achieved a pathological complete response, 6 (40%) a pathological partial response, for an overall response rate of 53% (95% confidence limits 29-77%). The median durations of response were 54 months for patients with a pathological complete response and 15.5 months for patients with a pathological partial response. One of six patients with a pathological partial response and 4 of 7 with no remission died of cancer. While a positive relationship between the pathological response and prognosis was observed, adequate follow-up is needed to assess the ability of neoadjuvant chemotherapy to improve the prognosis of patients with locally advanced urothelial cancer of the upper urinary tract.

Limitations of ureteroscopy in diagnosis of invasive upper tract urothelial cancer.

The efficacy of ureteroscopic evaluation of upper tract abnormalities was evaluated in 40 patients. Twenty-eight patients presented with a radiologic filling defect, 9 with a filling defect and hematuria and 3 individuals exhibited hematuria alone. Cold cup biopsies revealed transitional cell carcinoma in 7 of 9 patients with papillary tumors and in 2 of 3 with nonpapillary tumors. Four patients without ureteroscopic diagnosis of urothelial cancer were found to have invasive tumors on subsequent nephroureterectomy. Of 15 patients with upper tract urothelial cancer, 12 were treated with total nephroureterectomy. Three individuals with grade 1 neoplasms received conservative ureteroscopic ablative therapy. Ureteroscopy is effective when combined with biopsy in the diagnosis and treatment of papillary lesions, but exhibits a low sensitivity in patients with invasive lesions.

Myocardial ischemia after treatment with methotrexate, etoposide and cisplatin

Cisplatin exerts an additional influence on myocardial ischemia induced by the cardiovascular effects of etoposide. Two cases of myocardial ischemia related to combination chemotherapy with methotrexate, etoposide and cisplatin are reported. While the major toxicity associated with systemic chemotherapy is hematologic, it is suggested that, in elderly patients with increased incidence of atherosclerotic disease, special attention be given to vascular complications of antineoplastic agents.

Preliminary Results of Methotrexate, Etoposide and Cisplatin in the Treatment of Urothelial Cancer

Thirty-seven patients with urothelial cancer were given combination chemotherapy with methotrexate, etoposide and cisplatin. Thirty patients were evaluated for response. Response rates were 50% in the primary organ, 50% in the lymph nodes, 0% in lung and bone lesions. Two patients (7%) had a complete response and 12 (40%) had a partial response, for an overall response rate of 47%. The overall response rate rose to 57% in 7 patients treated with escalated doses of methotrexate and cisplatin. The median durations of response were 14 months for complete responders and 16 months for partial responders. Of the 30 evaluable patients, 16 (53%) are alive at a median survival of 30 months. The toxicity of the present regimen was acceptable. The methotrexate-etoposide-cisplatin combination chemotherapy seems to be an effective and safe regimen for urothelial cancer.

M-VEC (methotrexate, vinblastine, epirubicin, and cisplatin) with granulocyte colony-stimulating factor for the treatment of urothelial cancer : an effective and safe chemotherapy regimen

The toxicity of combination chemotherapy is significant, with the most prominent side effect being myelosuppression. To reduce the toxicity, we used a recombinant human granulocyte colony-stimulating factor (rhG-CSF). A total of 52 patients were enrolled in this study. The sites of tumor involvement included the urinary bladder in 24 patients, the renal pelvis in 5, the ureter in 4, lymph nodes in 11, bone in 4, the lung in 1, and miscellaneous sites in 4 patients. The chemotherapy was given in 21-day cycles as follows: 30 mg/m2 methotrexate was given intravenously on day 1, and approximately 24 h later, 3 mg/m2 vinblastine, 30 mg/m2 epirubicin, and 70 mg/m2 cisplatin were given intravenously. The rhG-CSF (2 μg/kg per day) was injected subcutaneously on days 3–16 of each cycle. All patients received full doses of the antineoplastic agents on time according to the protocol design. The response rates were 61% for primary sites, 55% for lymph nodes, 0 for bone, and 67% for miscellaneous sites. Of 42 patients evaluated, 5 (12%) achieved a complete response and 20 (48%) achieved a partial response, for an overall response rate of 60%. Of the 42 patients, 27 (64%) are alive, and the median duration of survival is 14 months. The mean nadir white blood count was more than 5,600 cells/mm3. the incidence of mucositis in the total toxic symptoms was low. There was no cardiac toxicity or drug-related death. These results indicate that the present combination chemotherapy with coadministration of rhG-CSF is an effective and safe regimen for the treatment of urothelial cancer.