[Topical immunotherapy (KLH) vs. chemotherapy (Ethoglucid) in prevention of recurrence of superficial bladder cancer. A prospective randomized study]. / Topische Immuntherapie (KLH) vs. Chemotherapie (Ethoglucid) in der Rezidivprophylaxe oberflächlicher Harnblasenkarzinome. Eine prospektiv randomisierte Studie.

A prospective randomized controlled study on the effect of KLH (keyhole limpet hemocyanin) versus etoglucid in the prevention of recurrences in primary and recurrent superficial transitional cell carcinoma of the bladder (stage pTa-pT1, grades 1-3 according to the recommendations of UICC and WHO) after complete transurethral resection of the tumor started in 198. Patients in group 1 (n = 76) were immunized with 1 mg KLH intracutaneously, after which they received bladder instillations of 30 mg (30 ml) KLH weekly for 6 weeks and then monthly for 1 year. Patients in group 2 (n = 85) received weekly bladder instillations of 0.565 g etoglucid (50 ml 1% solution) for 6 weeks and then monthly for 1 year. The percentage of recurrences, recurrence rate, disease-free interval and tumor progression rate were evaluated for both treatment groups. The end-point of the study was progression in stage or grade or more than two recurrences during the observation period. The shortest follow-up was 12 months, the mean follow-up, 27.5 months. No statistically significant differences were found between the two groups in percentage of recurrences (43.4% KLH-53.9% etoglucid), recurrence rate (4.4 KLH-3.9 etoglucid), mean disease-free interval (12.1 months KLH-13.6 months etoglucid) or progression rate (6.5% KLH-9.4% etoglucid).

Complications of intravesical chemotherapy.

A variety of intravesical chemotherapeutic agents are now available for the treatment of superficial transitional-cell carcinoma of the bladder. The toxicities associated with these agents may make one more appealing than another in the face of similar efficacies. Intravesical instillations of thiotepa have resulted in incidences of leukopenia of 8% to 54%, of thrombocytopenia of 3% to 31%, and of irritative voiding symptoms of 12% to 69%. Close monitoring of blood counts prior to weekly instillations remains vital in preventing myelosuppressive complications. The complications associated with the intravesical use of mitomycin C are mainly chemical cystitis and contact dermatitis. Additionally, allergic reactions have been documented. Most of these complications respond to cessation of therapy with application of topical steroids as needed. Complications of reduced bladder capacity, bladder-wall calcifications, and myelosuppression are uncommon. Toxicities associated with the use of doxorubicin, epirubicin, and ethoglucid are almost exclusively local and usually described as mild to moderate dysuria, frequency, or urgency. Case reports of systemic reactions to doxorubicin are notable in that the patients responded well to diphenhydramine and, in one severe case, epinephrine. Other adverse effects such as reduced bladder capacity, fever, and nausea and vomiting are very uncommon. New agents, such as mitoxantrone, are undergoing phase I and phase II studies. The ideal agent, which would be highly effective and minimally toxic, remains to be developed.

Prospective, randomized trial to evaluate high-versus low-dose interferon-alpha 2b versus conventional chemotherapy in prevention of the recurrence of superficial transitional cell carcinoma of the urinary bladder.

Forty-four patients with superficial bladder cancer were randomized to receive 10 MU (14 patients) or 100 MU (14 patients) of interferon (IFN)-alpha 2b or 1.3 g ethoglucid (16 patients) instilled into the bladder once weekly for 10 weeks and then monthly for 1 year. Efficacy (evaluated in 34 patients who completed the course of treatment), based on recurrence rate and time to first recurrence, was similar in the three groups. No systemic toxicity of treatment was seen. Severe chemocystitis occurred in some patients who received ethoglucid (three had to discontinue treatment), while no local toxicity was seen with IFN-alpha 2b treatment.

Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma.

Two cases are reported of patients who developed a hematologic malignancy several years after intravesical chemotherapy of superficial bladder cancer with etoglucid, doxorubicin, and mitomycin C. In one patient, karyotypic abnormalities (-5, 7q-) typical of a therapy induced malignancy were associated with rapid progression of a refractory anemia with excess blasts in transformation to an acute non-lymphocytic leukemia. Intravesical chemotherapy may be associated with a risk of secondary malignancy.

Intravesical ethoglucid (Epodyl) for treatment of noninvasive bladder cancer (stage Ta).

Widespread, well differentiated (grade I) bladder tumours confined to the mucosa (stage Ta) were treated with regular intravesical instillations of ethoglucid (Epodyl) in 24 patients. The therapeutic schedule could be followed in all but one patient, in whom side effects necessitated cessation of treatment. Complete response was obtained in 75% of the patients, and during continued prophylactic therapy 90% remained tumour-free. After termination of the treatment, however, new tumours appeared in 60-80% of the patients.

Adjuvant chemotherapy of superficial transitional cell bladder carcinoma: preliminary results of a European organization for research on treatment of cancer. Randomized trial comparing doxorubicin hydrochloride, ethoglucid and transurethral resection alone.

Patients with superficial transitional cell carcinoma of the bladder were entered in a randomized clinical trial to compare the efficacies of transurethral resection alone or followed by bladder instillation of doxorubicin hydrochloride or ethoglucid (Epodyl) for 1 year. Results showed that adjuvant chemotherapy with the selected drugs prolonged the mean interval between recurrences. Mild systemic toxicity and chemical cystitis were observed in 3 and 3 per cent, respectively, of the patients given ethoglucid, and in 5 and 4 per cent, respectively, of those taking doxorubicin.

Intracavitary Epodyl for multiple non-invasive, highly differentiated bladder tumours.

Multiple, recurrent cancer of the bladder grade I-II (WHO), stage T1 (UICC) was treated with regular intravesical instillation of ethoglucid (Epodyl) in 39 patients. In ten of them cystitis necessitated withdrawal of the treatment. The therapeutic schedule could be followed in 29 cases, with eradication of the tumours in 27. Nine patients who continued the treatment on a prophylactic basis were still recurrence-free after 18-60 (mean 37) months. Myelosuppression did not occur, but cystitis was a serious problem that frequently jeopardized therapy.

Epodyl treatment of bladder tumours.

Multiple, non-invasive bladder papillomas were treated with intravesical instillation of Epodyl in 44 patients. Irritative cystitis occurred in 16 per cent of the series, and in these cases Epodyl treatment had to be stopped. Total or partial disappearance of the papillomas was seen after 16 months of treatment in 43% of the total series. This was the minimum success rate, since all the patients who left the study were counted as failures. When the treatment could be carried through, total or partial disappearance of papillomas occurred in 19 of 29 patients (66%). Epodyl has a place in the treatment of vesical papillomas when other methods have failed.

Epodyl in management of noninvasive vesical neoplasms.

A prospective study to assess the effects of triethylene glycol diglyceridyl ether (Epodyl) in the management of superficial noninvasive vesical neoplasm (T1) is presented. Apart from a few local side effects, the response of the tumor to Epodyl was very good as assessed up to three years. Further long-term studies are being done.

The acute effects of various cytotoxic compounds injected into the prostate glands of dogs.

The acute effects of direct injections with various cytotoxic compounds into the prostates of adult dogs were studied microscopically. The effects remained localised to the site of injection, with no diffusion of the agents into other areas of the prostate. No systemic effects were observed despite the high concentrations used. The main histological changes consisted of local aseptic necrosis at the injection site surrounded by atrophy of the acinar epithelium.

Intravesical epodyl in the management of bladder tumors: combined experience of the Yorkshire Urological Cancer Research Group.

Of 48 patients with bladder tumors treated with intravesical epodyl 17 have shown a complete remission at some stage of treatment, although several have relapsed later. Partial remission occurred in 20 patients and 11 have shown no improvement or the lesions have progressed. Epodyl is used best as an adjunct to transurethral resection or diathermy of T1 bladder lesions. Even in patients who do not show complete remission epodyl may reduce the incidence of recurrence and the number of lesions. It is useful when rapid recurrence of T1 bladder tumors prevents control by resection or diathermy and it also is beneficial as an emergency measure to control hematuria. Complications are not infrequent and may be severe occasionally. Bone marrow depression has been seen in 2 patients whose bladders showed extensive carcinoma in situ.