Experimental and clinical studies on anal submucosal injection of methotrexate for bladder cancer
Yoshida, T.; Ogawa, T.; Fujinaga, T.; Kyoku, I.
Hinyokika Kiyo. Acta Urologica Japonica 37(8): 857-861
1991
ISSN/ISBN: 0018-1994 PMID: 1957728 Document Number: 372124
The experimental and clinical studies were performed to investigate the efficacy of the anal submucosal injection (ASI) of methotrexate (MTX) for bladder cancer. In the experimental study, MTX was administered to male Wister rats each weighing from 200 to 250 gm in a dosage of 2 mg/kg body weight through two different routes, one of which was intravenous injection (IV group) and the other of which was anal submucosal injection (ASI group). The concentrations of MTX in serum and bladder tissue after injection were estimated in both groups. Serum MTX levels in ASI group were significantly higher than those in the IV group from 30 minutes through 120 minutes after injection, while the IV group was higher than the ASI group at 5 minutes after injection. Tissue MTX levels in ASI group were significantly higher than those in the IV group from 60 minutes through 120 minutes after injection. However, tissue MTX levels in IV group were significantly higher than those in ASI group from 5 minutes through 15 minutes after injection. We started clinically to use ASI for bladder cancer as a preliminary random trial in November, 1988. Between November, 1988 and September, 1989 ASI was performed in 9 patients with various bladder cancer. The dose of MTX was 50 mg every week for 5 consecutive doses. The course was repeated at 3-week intervals. Only 3 patients were evaluable for the clinical efficacy of ASI. Two patients with CIS showed complete regression and the other patient with superficial low grade tumor had no changes. Five patients who had at least one course of treatment were evaluated for their toxicities. It was noted that all patients encountered stomatitis which was regarded as one of the systemic side effects. Furthermore serum MTX concentrations were measured 30 minutes, 1, 3, 6 and 24 hours after administration in both the ASI group and IV group. In the IV group the same dose of MTX was administered intravenously by one-hour drip infusion. Serum MTX levels in the ASI group were significantly higher than those in the IV group from 1 hour through 6 hours after injection, which was consistent with our experimental results. Further study should be needed to assess the efficacy of this treatment for bladder cancer.