estramustine and Urinary-Bladder-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

Failure of epirubicin treatment of superficial bladder cancer implies multidrug resistance (MDR) which is common. MDR is characterised by decreased cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to both epirubicin and mitomycin C were used to investigate augmented therapy by adding the MDR reversing agent estramustine to an in vitro model.. Cells were cultured as monolayers. Fluorescence analysis was performed by flow cytometry and confocal microscopy. Cells were exposed to epirubicin 20 microg/ml for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under similar exposure conditions and MTT culture (dye reduction by live cells) allowed viable biomass to be read optically.. Resistant cells accumulated eight times less epirubicin than sensitive cells. Confocal microscopy confirmed this for nuclear uptake. Accumulation in resistant cells can be increased to near-sensitive cell levels using 40 microg/ml estramustine. Image analysis of confocal fluorescence showed a shift from cytoplasm to nucleus. This correlated with increased cytotoxicity.. Estramustine plus epirubicin chemotherapy can overcome MDR and may achieve more successful tumour killing in vivo. It may also prevent emergence of resistance. Primary TCC culture examination permits detection of sensitive and resistant cells and may predict outcome allowing a more logical treatment selection.

Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Carcinoma, Transitional Cell; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Epirubicin; Estramustine; Flow Cytometry; Fluorescence; Humans; Microscopy, Confocal; Tumor Cells, Cultured; Urinary Bladder Neoplasms