Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the management of superficial transitional cell cancer of the urinary bladder.

OBJECTIVE: To investigate the utility of an individualized chemo/immunotherapy regimen of intravesical therapy based on the results of an assessment of in vitro cytotoxicity.

PATIENTS AND METHODS: Intravesical adjuvant chemo/immunotherapy was given to 47 patients based on the results of in vitro cytotoxicity assay of the responses of cultured autologous tumour cells to various cytotoxic drugs (mitomycin-C, doxorubicin and cisplatin) and immunomodulating agents (bacillus Calmette-Guérin, BCG and interferon-alpha2b). Intravesical therapy was given as single- or double-drug regimens according to the assay results: 16 (34%) patients showed cytotoxicity to a single drug and 31 (66%) showed maximum cytotoxicity to a combination of immunomodulators and cytotoxic agents. The efficacy of treatment in terms of tumour-free survival and recurrence rate was compared with 40 patients receiving intravesical BCG according to International Protocol (control group).

RESULTS: In the in vitro assay group, seven patients (15%) had tumour recurrence, compared to 15 (38%) in the control group (P = 0.02). In the in vitro group, one of 16 patients on a single drug and six on the double-drug regimen had a recurrence. The patients given BCG with cytotoxic drugs had no recurrences, but 29% of patients given interferon-alpha2b combinations had recurrences. Kaplan-Meier analysis showed a longer recurrence-free survival in the in vitro group (75%) than in the control group (49%) at 48 months of follow-up.

CONCLUSION: Intravesical therapy based on an in vitro cytotoxicity assay is an attempt to give individualized therapy, and to increase tumour-free survival in these patients, with no side-effects. Recurrences in seven patients in the in vitro group might be due to a defective host immune response, or to expansion of a subclone of tumour cells resistant to all treatment.