Mitsutaka Ueda

Usefulness and Limitations of Methotrexate, Vinblastine, Doxorubicin And Cisplatin for the Treatment of Advanced Urothelial Cancer

Methotrexate, vinblastine, doxorubicin and cisplatin were used to treat 66 patients with advanced urothelial cancer. Of these 66 patients 58 could be evaluated for response. A total of 84 sites was evaluated in these patients. Response rates were 73% in the bladder, 67% in the renal pelvis, 50% in the ureter, 60% in the lung, 68% in the lymph nodes, 14% in the liver and 25% in the bone. Ten patients (17%) had a complete response and 23 (40%) had a partial response, with an over-all response rate of 57% (the 95% confidence limits are 44 to 69%). The mean durations of response were 10.1 months for complete response patients and 6.2 months for partial response patients. The most prominent toxicity was severe myelosuppression that resulted in 2 septic deaths. While this chemotherapy regimen provided an excellent over-all response rate, the matters of concern were the short duration of response and low effectiveness in the liver and bone.

Metastatic Renal Cell Carcinoma Arising in a Native Kidney of a Renal Transplant Recipient

We report a case of metastatic renal cell carcinoma arising in the native kidney of a renal transplant recipient. A 39-year-old man, who had undergone living renal transplantation from his mother at age 32, presented with complaints of paraplegia of the leg caused by a pathological fracture of the 3rd lumbar vertebra. The bone tumor was extirpated and pathological examination revealed metastatic adenocarcinoma. Abdominal computerized tomography showed a tumor in the right native kidney. Right nephrectomy and resection of the right 7th rib tumor were performed. Pathological evaluation demonstrated renal cell carcinoma of the right native kidney (pT2bpN0pV0M1, mixed cell type, grade 2). Postoperatively, cyclosporine was discontinued and natural interferon-alpha was given. The remaining bone metastasis had completely resolved with no significant sign of rejection 1 year after surgery.

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.

Factors affecting the outcome of patients with advanced urothelial cancer following chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin.

SummaryAttempts were made to identify factors related to the response of patients treated with intravenous methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC). The subjects consisted of 54 patients with advanced urothelial cancer whose histological type was transitional-cell carcinoma. The effects of various factors on the response were studied using univariate analysis and a multiple logistic regression model. The following factors were included in the anlayses: (1) age, (2) sex, (3) performance status (PS), (4) primary site, (5) histological grade, (6) T category, (7) N category, (8) M category, (9) tumor status, and (10) dose of drugs. In all, 9 patients achieved a complete response and 23 showed a partial response, for an overall response rate of 59% (95% confidence limits, 46%–72%). Univariate analysis revealed that the PS, M category, and dose of drugs were related to the response, and there was a significant correlation among these three factors. In the multiple logistic regression model, the absolute value oft was high for the M category. The presence of distant metastases is an important factor in predicting poor efficacy for the present regimen. The management of metastatic disease will be the subject of further study in the treatment of advanced urothelial cancer.

Analyses of factors affecting the outcome of combination chemotherapy in patients with advanced bladder cancer.

Thirty-seven patients with advanced bladder carcinoma were treated with a combination of methotrexate, vinblastine, adriamycin and cisplatin (M-VAC). Attempts were made to identify the factors related to the results of the present regimen using multivariate analyses. Factors related to the results were presence of distant metastases and prior chemotherapy. The effect of the M-VAC chemotherapy was disappointing in most patients with distant metastases and prior chemotherapy. This was prominent in patients with prior chemotherapy including cisplatin. These results seem to show clinically the development of resistance to cisplatin in advanced bladder cancer. Methods to overcome this resistance should be studied.

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.