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Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the management of superficial transitional cell cancer of the urinary bladder
Author(s) -
Saxena Sunita,
Agrawal Usha,
Agarwal Abhilasha,
Murthy Nandagudi Srinivasa,
Mohanty Nayan Kumar
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06482.x
Subject(s) - cytotoxicity , medicine , immunotherapy , adjuvant , regimen , cytotoxic t cell , cisplatin , in vitro , urology , bladder cancer , adjuvant therapy , chemotherapy , pharmacology , oncology , immunology , cancer , biology , biochemistry
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‐α2b). 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‐α2b 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.