Influence of Thiotepa and Doxorubicin Instillation at Time of Transurethral Surgical Treatment of Bladder Cancer on Tumor Recurrence: A Prospective, Randomized, Double-Blind, Controlled Trial

Abstract

The influence of the instillation of thiotepa or doxorubicin hydrochloride into the bladder at the end of transurethral surgical treatment on the recurrence of bladder cancer was evaluated. We studied in a randomized, double-blind, controlled fashion 89 patients with transitional cell epithelioma (carcinoma in situ or papillary carcinoma) whose tumors were considered to have been completely removed. Of these patients 28 (the control group) received a placebo (sterile water), 30 received thiotepa and 31 received doxorubicin. By 3 to 4 months postoperatively 71 per cent of the control group, and 30 and 32 per cent, respectively, of the patients treated with thiotepa and doxorubicin had recurrences (p less than 0.01). Additional treatment during the followup interval was ineffective in all groups. Patients studied also were classified according to grade, histological findings, multiplicity of tumors and history of bladder tumor. Treatment was most effective in reducing recurrence in patients with low grade, papillary or multiple tumors and in patients with a history of bladder cancer. No effect was observed in patients with single tumors and only modest effects were found in those with high grade tumors, carcinoma in situ or new tumors. The results support the concept that recurrences may arise from tumor cell implantation at the time of transurethral management of bladder tumors and may be reduced effectively by concomitant intravesical chemotherapy.

Randomized study of single early instillation of (2″R)‐4′‐O‐tetrahydropyranyl‐doxorubicin for a single superficial bladder carcinoma

“…However, they could not find any effect in patients with a single tumor. 15 Oostelinck et al first demonstrated that a single instillation clearly prevented recurrence for patients with a single tumor. 6 Tolley et al stated that a single instillation can prevent recurrences of patients with either a single or multiple tumors.…”

Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

“…Review of these initial studies identified nine controlled trials including 1130 patients. Reviewing five of the trials that achieved statistical significance, 84,[88][89][90][91] the mean rate of recurrence in the control populations was 61% versus 49% in the treated groups, resulting in a modest 12% benefit with thiotepa therapy. 69 Currently, due to its marginal efficacy and risk of systemic toxicity, use of thiotepa is limited to patients who cannot tolerate BCG or selected BCG-refractory cases not medically fit for cystectomy.…”

Current Insights in the Treatment of Superficial Transitional Cell Carcinoma of the Bladder

“…In large studies comparing different chemotherapeutic agents, none of the chemotherapeutic agents turned out to be superior [10][11][12][13] (table 1). There is no accordance in dose, treatment schedule, time to start and dura tion of instillation therapy, all schemes are mainly empirical.…”