Polymyalgia rheumatica with temporal arteritis following intravesical Calmette-Guérin bacillus immunotherapy for bladder cancer.
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An early phase II study (dose-finding study) of amrubicin hydrochloride for superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of physiological saline and injected intravesically for 6 consecutive days. The drug solution was retained for 2 hours. Patients were randomly assigned to four groups, which were administered amrubicin at doses of 30, 60, 90, and 120 mg/day, respectively. Of 65 patients registered in this study, 63 were eligible and assessable for toxicities, and 55 assessable for efficacy. The response rate at each dose level was 50.0% (7PRs/14 patients) at 30 mg/day, 53.3% (8 PRs/15) at 60 mg/day, 61.5% (2 CRs + 6 PRs/13) at 90 mg/day, and 69.2% (2 CRs + 7 PRs/13) at 120 mg/day, respectively. These data suggests that the efficacy was related to the doses of amrubicin. The major toxicities were cystic irritabilities, such as micturition pain, pollakisuria and hematuria. These toxicities were related to the doses of amrubicin. Their incidence and the severity were not high compared with those reported about other anthracyclines such as doxorubicin and epirubicin. The optimal dose of amrubicin was estimated to be 90 to 120 mg/day in the intravesical treatment for superficial bladder cancer once a day for 6 consecutive days.
The anti-tumor effect of OK432 instilled into the bladder was evaluated in rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment I, the rate of the natural killer (NK) activity was determined with cells from spleen and mesenteric lymph nodes. Intravesical OK432 instillation enhanced NK activity; however, this activity was not dose-dependent and was not augmented by OK432 inoculation into the foot pad. In experiment 2, the therapeutic effect of intravesical OK432 instillation was examined in rat bladder tumors induced by BBN. OK432 was instilled weekly for six weeks. Rats given BBN for 10 weeks were divided into six groups: 1) control; 2) saline; 3) OK432 0.05 KE/ml; 4) OK432 0.05 KE/ml bladder instillation with 0.01 KE/ml foot pad inoculation; 5) OK432 0.05 KE/ml, every other week; and 6) OK432 0.5 KE/ml. Weekly OK432 instillation significantly reduced tumor weight and the incidence of tumor development; however, this inhibition was not dose-dependent and was not enhanced by OK432 inoculation into the foot pad. In rats given OK432 weekly, the augmentation of NK activity and increase in tissue infiltrating lymphocytes were significant. These results suggest that intravesical OK432 instillation is effective in the management of superficial bladder tumors. The study further emphasizes that the dose and method of administration are critical variables in determining the efficacy of immunotherapy.
From our experimental study, an instillation of THP for 5 minutes was attempted in 23 patients with superficial bladder tumors. THP (30 mg dissolved in 50 ml of distilled water) was instilled into the bladder 6 times every 48 hours. Of 23 patients, 9 (39%) showed complete disappearance of the bladder tumors, while partial disappearance (more than 50% tumor reduction) was observed in 3 cases (13%). Therefore the overall response rate was 52%. Neither urinary frequency nor hematuria was observed in all the cases, while painful urination was observed in 3 cases (13%). This newly designed bladder instillation therapy was effective against superficial bladder tumors with low incidence of local side effects.
Transurethral surgery is the primary treatment for patients with superficial bladder cancer. Either electrical or laser thermal destruction is used most often but there is no proven therapeutic benefit for one method over the other. Treatment failure is usually a consequence of new tumor occurrence rather than the failure to eradicate existing visible tumors. Adjuvant intravesical chemotherapy or immunotherapy improves results over surgery alone in most circumstances.
The absorption of Adriamycin (ADM) into the systemic circulation and into different organs including the urinary bladder was investigated in the rat after intravesical instillation of ADM with or without a surface active detergent, Tween 80. The postinstillation plasma concentration of ADM increased significantly with increasing dose of the drug. Even though the leakage of ADM into the systemic circulation and into extravesical organs in general was slight a significant increase was observed after addition of Tween 80. The uptake of ADM into the urinary bladder wall was also significantly enhanced by Tween 80 thus the role of this agent in conjunction with intravesical chemotherapy should be further investigated.
Intravesical mitomycin C is an effective agent for treatment of superficial transitional cell carcinoma of the bladder. A 60 to 70 per cent overall response rate has been reported. Its side effects have been minor. We present a case of severe bladder contracture after intravesical therapy with mitomycin C.
The present study investigated the potential of intravesical instillation for localized reduction of NGF (nerve growth factor) expression in the urinary bladder. Overexpression of NGF has been linked to the pathogenesis of interstitial cystitis (IC). A minimum free energy algorithm was used to predict suitable regions in mRNA of rat betaNGF, which can be targeted for an antisense approach. The candidate antisense oligos were evaluated for their ability to reduce NGF expression in vitro by cotransfecting HEK293 cells with NGF cDNA. A single oligonucleotide ODN sequence was chosen for testing in an acute cystitis model in rat induced by cyclophosphamide. Overexpression of NGF is known to mediate inflammation of bladder in this model. For improved stability, antisense ODN was replaced with antisense peptide nucleic acid (PNA) and its penetration into bladder was facilitated by tethering TAT peptide sequence. Rat bladders were instilled with either antisense or its scrambled control prior to cystitis induction. Cystometrograms performed on rats under urethane anaesthesia exhibited bladder contraction frequency that was significantly decreased in the antisense treated rats than rats treated with the control. NGF immunoreactivity was also decreased in the urothelium of the antisense treated bladders. Our findings demonstrate the feasibility of using TAT-PNA conjugates for intravesical antisense therapy.
Thirty three patients with carcinoma in situ (CIS) or/and numerous recurrences of superficial bladder tumor were treated with intravesical BCG after transurethral resection. 63% of patients with CIS were free of recurrence after two years, two underwent cystectomy and one died because of progression. Patients with Ta and concomitant CIS responded well to BCG, while the patient with T1 tumor and CIS was free from recurrence for 15 months. Dysplasia of grade II disappeared after BCG. 62% of patients with Ta tumor were without recurrence after one year, but after two years 86% of the patients had recurrences. Patients with T1 tumor were free from recurrence for eight months, after which 25% had progression. The side effects of BCG were transient: urinary frequency in 48%, malaise in 39%, dysuria in 36%, haematuria, bladder pain and fever in 24%. 15% of the patients required isoniazid treatment. It is concluded that intravesical BCG is beneficial in CIS and superficial bladder tumors.
Early radical cystectomy for a high-grade tumor invading the lamina propria (T1) remains controversial. In 1997, we cannot identify accurately which of these high-risk tumors will progress to muscle-invasive disease and metastases. In the near future, urologists may be able to use the presence of genetic alterations, such as p53 mutations, to help make therapeutic decisions. Previous reports on superficial bladder cancer treated with intravesical bacillus Calmette-Guérin immunotherapy have demonstrated a decrease in recurrence and progression. Unfortunately, there is no reliable method to predict which patients with a high-grade T1 tumor will fail to respond to intravesical therapy. Failure of intravesical therapy to control these aggressive tumors is associated with a significant rate of pathological upstaging and metastases. Radical cystectomy will cure a high percentage of these T1 tumors with acceptable morbidity and low mortality. In an era of nerve-sparing cystectomy and orthotopic neobladder reconstruction, early radical cystectomy is an alternative that should be discussed with the patient before instituting intravesical therapy.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.