isotretinoin and Urinary-Bladder-Neoplasms

Topics: Animals; Antineoplastic Agents; beta Carotene; Butylhydroxybutylnitrosamine; Carcinoma in Situ; Carcinoma, Papillary; Carotenoids; Cell Differentiation; Dose-Response Relationship, Drug; Epithelium; Fenretinide; Humans; Isotretinoin; Neoplasms; Neoplasms, Experimental; Tretinoin; Urinary Bladder Neoplasms; Vitamin A

Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study.

Topics: Carcinoma, Transitional Cell; Follow-Up Studies; Humans; Incidence; Isotretinoin; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Urinary Bladder Neoplasms

In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.

Topics: Carcinoma, Basal Cell; Clinical Trials as Topic; Etretinate; Humans; Isotretinoin; Keratosis; Photosensitivity Disorders; Skin Neoplasms; Tretinoin; Urinary Bladder Neoplasms

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Humans; Isomerism; Isotretinoin; Methotrexate; Mitomycin; Mitomycins; Neoplasm Recurrence, Local; Random Allocation; Registries; Thiotepa; Tretinoin; Urinary Bladder Neoplasms

The collaborative group chemotherapy studies of the National Bladder Cancer Project are summarized with regard to intravesical and systemic agents. The necessity for longitudinal observations and data collection in all cases of bladder cancer, and not just those receiving chemotherapy, is also stressed.

Topics: Adult; Aminoacridines; Amsacrine; Antineoplastic Agents; Carcinoma in Situ; Carcinoma, Papillary; Cisplatin; Clinical Trials as Topic; Drug Evaluation; Humans; Isotretinoin; Mitomycin; Mitomycins; Multi-Institutional Systems; Neoplasm Recurrence, Local; Thiotepa; Tretinoin; Urinary Bladder Neoplasms

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

Topics: Alitretinoin; Antineoplastic Agents; Dose-Response Relationship, Drug; Humans; Isotretinoin; Time Factors; Tretinoin; Tumor Cells, Cultured; Urinary Bladder Neoplasms

The prophylactic effect of 2 retinoids (Ro 4-3780 and Ro 10-9359), either alone or in combination with Bacillus Calmette Guérin (BCG), was studied in an experimental murine bladder tumor model. The incidence of tumor takes in all treatment groups was lower than in the control group. Both BCG and Ro 10-9359 were effective in decreasing the percentage of tumor takes and the simultaneous use of these agents was more effective than either one alone. Ro 10-9359 was found to possess more antitumor activity than Ro 4-3780 in this tumor model. Treatment of mice with a combination of Ro 10-9359 and BCG resulted in an 83.3 per cent incidence of complete tumor regression within 80 days. Results suggest that vitamin A derivatives may be useful in the prevention and treatment of bladder cancer and that the activity is likely potentiated by nonspecific stimulation.

Topics: Animals; BCG Vaccine; Etretinate; Female; Isotretinoin; Mice; Mice, Inbred C3H; Neoplasms, Experimental; Tretinoin; Urinary Bladder Neoplasms

The failure of 13-cis-retinoic acid to inhibit either the incidence or severity of bladder carcinoma in female Fischer rate initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) suggests that inhibition of bladder carcinogenesis by natural and synthetic retinoids is carcinogen-class specific, and adds an element of complexity to approaches in chemoprevention.

Topics: Animals; Butylated Hydroxytoluene; Carcinogens; FANFT; Female; Isomerism; Isotretinoin; Neoplasms, Experimental; Rats; Rats, Inbred F344; Thiazoles; Tretinoin; Urinary Bladder Neoplasms