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.
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.
1) Antitumor effect of intravesical instillation
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.
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.
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.
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.
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.
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%).
2) Histopathological changes of tumors by the instillation
Histopathological studies were performed in 12 cases with single regimen of thio-TEPA and in 8 cases with the three drug regimens instillation.
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.
2. Among the case with proved histopathological improvement, the mean dose of thio-TEPA was 320mg.
3. No specific correlation between histopathological effect and malignancy of the tumors was suggested.
3) Side effect of the intracavital chemotherapy
Leucopenia, bladder irritability and reduction of bladder capacity were common as side effects of the treatment.
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%).
2. Leucopenia was encountered in 6 of 11 cases (54.5%) in the combined group.
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.
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.
4) Absorption of the instillated drugs from the bladder mucosa
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.
Thio-TEPA was higher in blood compared with instillated dose. MMC and 5-Fu were next to it.
2. Recovery ratio of thio-TEPA from the urine was least among three agents mar
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