estramustine and Kidney-Neoplasms

We describe the progress in oral anti-cancer drug therapy for urological cancer. Pure antiandrogen (e.g., flutamide) is widely used as a means of maximal androgen blockade (MAB) in the treatment of prostate cancer. However, all series reported in the past several years did not show positive effects on prolongation of the patient's survival. Evaluations by meta-analysis are in progress. As the mechanism of antiandrogen withdrawal syndrome has been recognized, it was widely accepted that antiandrogen should be discontinued when disease progression or PSA elevation becomes evident. Estramustine was recently clarified as an effective therapeutic agent in the treatment of hormone refractory prostate cancer in combination with oral etoposide. Oral etoposide therapy has been tried as a maintenance or a palliative chemotherapy for non-curative or high-risk germ cell tumor. UFT (a compound of tegafur and uracil) is said to be effective for bladder cancer. It has been also suggested that UFT was partly effective as a means of first-line endocrine chemotherapy for advanced prostate cancer and was a promising agent in the treatment of advanced renal cell carcinoma in combination with Interferon-alpha. Usually the age of the patient with urological malignancy, excluding testicular cancer, is high and complicated. For such patients, an aggressive intravenous chemotherapy can not always be used. Therefore, a less aggressive, less toxic chemotherapy with oral drug is often planned to maintain QOL.

Topics: Administration, Oral; Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Drug Combinations; Estramustine; Etoposide; Female; Flutamide; Humans; Kidney Neoplasms; Male; Prostatic Neoplasms; Tegafur; Uracil; Urinary Bladder Neoplasms

It is well known that metastatic renal cell carcinoma (RCC) exhibits constitutive resistance to chemotherapeutic agents. Antimicrotubule agents such as vinblastine are associated with low but reproducible response rates (approximately 12%) in patients with RCC. Estramustine has been shown to potentiate the antimicrotubule effects of vinblastine. The authors sought to increase the activity of vinblastine in RCC through the addition of estramustine.. Twenty-one patients with metastatic RCC not previously treated with chemotherapy received oral estramustine phosphate, 600 mg/m(2), on Days 1, 2, and 3 weekly for 6 weeks, and intravenous vinblastine, 4 mg/m(2) on Day 2 weekly for 6 weeks, repeated every 8 weeks. Twenty-one patients received 31 cycles of therapy.. Two patients experienced Grade 3 and 4 hematologic toxicity, and three patients had Grade 3 nonhematologic toxicity consisting of neurologic toxicity, hepatic toxicity, or angioneurotic edema. One patient had a partial response with decreased liver metastases for 48 weeks; 9 patients had stable disease, for a median duration of 14 weeks (range, 11-31 weeks); and 11 patients demonstrated disease progression. The median overall time to progression was 8 weeks and the median overall survival period was 24 weeks.. Although well tolerated, the combination of oral estramustine phosphate with vinblastine administered on this schedule had minimal activity in patients with metastatic RCC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Drug Administration Schedule; Estramustine; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Survival Analysis; Vinblastine

Sixteen patients completed an adequate trial of estramustine phosphate for the management of metastatic renal cell carcinoma. Although no patient showed a complete or partial response, 9 (56 per cent) had stabilization of disease for a median of 44 weeks. Toxicity was not severe, but intolerance to the drug may limit its widespread use.

Topics: Adult; Aged; Clinical Trials as Topic; Estramustine; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Nitrogen Mustard Compounds; Sex Factors

The present report shows that the human renal cell carcinoma (RCC) cell lines, A498 and CAKI-2, express the estramustine-binding protein (EMBP). The RCC cell lines investigated were highly sensitive for estramustine, with cell arrest in atypical metaphase. In vitro experiments using a fluorimetric cytotoxicity assay (FMCA) showed a pronounced cytotoxic effect mediated by estramustine. Immunohistochemical analysis of tumour specimens from patients with RCC showed positive staining for EMBP in 12/16 cases. Immunoscintigraphy was performed in an experimental system in nude mice, heterotransplanted with the CAKI-2 cell line. A radiolabelled monoclonal anti-EMBP antibody was used. The results show a specific uptake of the antibody in the RCC tumour, expressed as a percentage of the injected dose per gram tissue, which ranged from 4.03 to 6.9. The results obtained form the basis for clinical studies on the feasibility of utilizing estramustine in the management of RCC. Immunoscintigraphy using the monoclonal anti-EMBP antibody is of potential use for in vivo characterization of the malignancy and in the selection patients suitable for treatment with estramustine.

Topics: Adult; Aged; Animals; Antineoplastic Agents, Hormonal; Carcinoma, Renal Cell; Carrier Proteins; Dose-Response Relationship, Drug; Estramustine; Feasibility Studies; Female; Fluorometry; Humans; Immunohistochemistry; Iodine Radioisotopes; Kidney Neoplasms; Male; Metaphase; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Prostatic Secretory Proteins; Radioimmunodetection; Transplantation, Heterologous; Tumor Cells, Cultured

Incubation with estramustine phosphate for 24 h inhibited DNA, RNA and protein synthesis in primary cultures of human kidney, mammary, prostatic, cervical and endometrial carcinoma. Not only the presence, but also the concentration of oestrogen receptors correlated with estramustine phosphate effects on tumour cell proliferation.

Topics: Cell Division; Cytosol; DNA, Neoplasm; Dose-Response Relationship, Drug; Estramustine; Female; Humans; Kidney Neoplasms; Leucine; Male; Prostatic Neoplasms; Protein Biosynthesis; Receptors, Estrogen; RNA, Neoplasm; Thymidine; Tumor Cells, Cultured; Uridine; Uterine Cervical Neoplasms; Uterine Neoplasms