EFFECTS OF INTRAVESICAL INSTILLATION OF ANTITUMOR AGENTS ON BLADDER CANCER

Intravesical instillation of thio-TEPA, Mitomycin C (MMC) and 5-Fluorouracil (5-Fu) with a single or triple drug regimens has been attempted on cases of urinary bladder tumors admitted in our hospital for four years from 1966 to 1969.<br>The instillation was usually carried out twice a week to reach total doses of thio-TEPA 300mg and MMC 100mg. Triple drug regimen instillation was tried with thio-TEPA 20mg, MMC 10mg and 5-Fu 500mg.<br>1) Antitumor effect of intravesical instillation<br>1. Thio-TEPA was applied to 29 cases of non-infiltrative bladder tumor, resulting in complete destruction in 6 cases (20.7%), partial destruction in 14 cases (48.3%) and ineffectiveness in 9 cases. On the other hand, partial destruction was observed in 14 cases (51.9%) and without effect in 13 cases (48.1%) of 28 cases of infiltrative tumor. Complete destruction was found in no case.<br>2. Based on the evaluation of partial destruction, prominent or moderate destructive findings of the tumors were examined cystoscopically in the non-infiltrative cases, whereas only superficial destruction was observed in the infiltrative cases.<br>3. The mean dose of thio-TEPA 367mg has been thought necessary to obtain complete destructive effect in non-infiltrative cases. However, even the mean dose of 234mg or 204mg seemed to show only partial destruction or no effect.<br>4. Non-infiltrative tumors smaller than pea-size prominently reduced in size or completely disappeared with doses of thio-TEPA less than 180mg. On the contrary, tumors larger than pea-size showed a reduction in size or disappearance with doses of thio-TEPA 250 to 300mg. Drug susceptibility might be evaluated by observing the superficial tumor change with the instillation of thio-TEPA 120mg.<br>5. MMC has been singly used on 17 cases of bladder tumor. 13 cases of them were non-infiltrative and the size of tumors was small. Complete disappearance of tumors was found in 3 cases out of these non-infiltrative cases.<br>6. Intravesical instillation of triple drug regimens was applied to 12 cases, resulting in complete destruction in one (8.3%), partial destruction in eight (75.0%) and without effect in 2 cases (16.7%).<br>2) Histopathological changes of tumors by the instillation<br>Histopathological studies were performed in 12 cases with single regimen of thio-TEPA and in 8 cases with the three drug regimens instillation.<br>1. Characteristic pathological changes such as reduction of tumor cells in number, vacuolation, pleomorphism, decrease of cohesiveness, piknosis and interstitial fibrosis were observed following the treatment.<br>2. Among the case with proved histopathological improvement, the mean dose of thio-TEPA was 320mg.<br>3. No specific correlation between histopathological effect and malignancy of the tumors was suggested.<br>3) Side effect of the intracavital chemotherapy<br>Leucopenia, bladder irritability and reduction of bladder capacity were common as side effects of the treatment.<br>1. Leucopenia was found in 30 of 42 cases (71.2%) with thio-TEPA instillation, thrombocytopenia in 16 of 21 cases (61.9%) and pancytopenia in 2 of 51 cases (3.6%).<br>2. Leucopenia was encountered in 6 of 11 cases (54.5%) in the combined group.<br>3. Bladder irritability was complained in 19 of 56 cases (34.0%), while decrease of bladder capacity was observed in 6 cases (10.7%) of the single drug regimen group.<br>4. On the other hand, bladder irritability was recognized in 5 of 12 cases (41.7%) and decrease of bladder capacity was found in 2 cases (16.7%) of the combined group.<br>4) Absorption of the instillated drugs from the bladder mucosa<br>1. Transmission of the drugs into blood was assumed in all 5 cases intravesically instillated with ³²P thio-TEPA and MMC, while 5-Fu was proved in blood in 3 of 5 cases.<br>Thio-TEPA was higher in blood compared with instillated dose. MMC and 5-Fu were next to it.<br>2. Recovery ratio of thio-TEPA from the urine was least among three agents mar