Treatment of Superficial Bladder Tumors in a Controlled Trial With Thio-TEPA Versus Adriamycin

Abstract

Forty-six patients with superficial transitional cell carcinoma of the bladder were randomized into two groups. Thio-TEPA or adriamycin were instilled periodically into the bladder and cystoscopic follow up was carried out. Both thio-TEPA and adriamycin proved to have similar efficacy in delaying tumor recurrence. Further investigations to establish better dose and interval schedules are indicated. KEY WORDS: urinary bladder, intravesical chemotherapy, thio-TEPA, adriamycinMany drugs havc been employed for topical chemotherapy of superficial recurrent transitional cell carcinoma of the bladder [I, 3, 4, 7, 8, 12-14]. Thio-TEPA was the first, and still widely used, drug in these conditions for both treatment and prophylaxis [4, 111. Adriamycin (doxorubicin hydrochloride) has also proven efficacious in reducing the recurrence rate of T I papillary tumors when employed prophylactically after transurethral resection [lo].We previously reported [4] our results of a randomized study conducted in patients with superficial cancer of the bladder who were treated with either intravesicular thio-TEPA or adriamycin. The present report extends our previous findings on a greater number of patients followed for a longer period of time. MATE:RIAL AND METHODSPatients with stage A tumors (infiltration not extending beyond the submucosa) or stage B, tumors (infiltration less than half way through the detrusor muscle) were referred to our department after previous recurrent transurethral resections and fulgurations. All patients had confirmed histological diagnosis of transitional cell carcinoma classified according to the Jewett-Strong classification (51 with the Marshall modification 161.Prior to initiating the treatment regimen, every patient underwent a bimanual palpation, cystoscopy, and biopsy. If tumor was present a transurethral resection was performed. Thus, the following intravesical chemotherapy (IVC) was considered to be prophylactic.All objective clinical parameters, if any, were recorded, and relevant blood tests, urinalysis, and radiographs were done before and at given intervals during treatment.Patients were randomized according to their order of referral, odd numbers receiving thio-TEPA and even numbers receiving adriamycin.Either 60 mg thio-TEPA or 50 mg adriamycin was dissolved in 70 cc of physiologic saline. The drug was instilled into the bladder through a sterile catheter and retained there for 2 hours, changing the patient's position every 15 minutes.Intravesicular instillations were initiated within 3 weeks of the pretreatment cystoscopy, and rcpcated at 3-week intervals. Following the third instillation (week 9) cystoscopy was repeated, followed by three additional instillation sequences, followed again by cystoscopy . This regimen lasted 36 weeks, with nine instillations and three cystoscopic evaluations (induction period). At the end of this 36-week period the frequency of treatment was reduced to once every 8 weeks (maintenance period), and cystoscopy was repeated every 24 weeks (weeks 60, 84, etc). The ...

The effect of high-dose thiotepa, alone or in combination with other chemotherapeutic agents, on a murine B-cell leukemia model simulating autologous stem cell transplantation

“…It has been used clinically in several conditions, including breast adenocarcinoma, 2 Hodgkin's disease, 5 ovarian adenocarcinoma 14 and transitional cell carcinoma of the bladder. 3,4 In the context of BMT, TH has been used for multiple myeloma, 6 breast carcinoma, 7 leukemia 8 and lymphoma 9 due to its relative safety and a low-toxicity profile (other than the expected myelosuppression), which render TH preferable over other agents when used in high-dose protocols, without causing further toxicity even in high-risk groups. 6 Yet, the role of TH in combination with other drugs in lymphatic diseases has not been sufficiently studied.…”

“…2 TH has been given intrathecally for carcinomatous meningitis, and intravesically for bladder carcinoma. 3,4 Mild-to-moderate activity was observed in several solid tumors and hematological malignancies. 1,5 There has been, however, a sustained interest in defining clinical roles for TH.…”

Intravesical Treatments of Bladder Cancer: Review

“…Chemotherapy Multiple chemotherapeutic agents, such as mitomycin C (MMC) ( 21 – 25 ), doxorubicin ( 26 – 28 ), epirubicin ( 29 – 32 ), thiotepa ( 33 , 34 ), ethoglucid ( 35 – 37 ), valrubicin ( 38 – 40 ), cisplatin ( 41 – 43 ), gemcitabine ( 44 – 46 ), suramin ( 47 , 48 ) or their combinations ( 49 – 52 ) have been evaluated in patients; meta-analyses did not show apparent superiority of a particular treatment. The addition of intravesical chemotherapy to TUR yields, on average, a further reduction of recurrence by 14–17%, but has limited benefits against disease progression ( 53 ).…”