title: Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the management of superficial transitional cell cancer of the urinary bladder.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology, ICMR, New Delhi, and Safdarjang Hospital, New Delhi, India. sunita_saxena@yahoo.com
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
authors.forename: Usha
authors.initials: U
authors.lastname: Agrawal
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Agarwal
authors.forename: Nandagudi Srinivasa
authors.initials: NS
authors.lastname: Murthy
authors.forename: Nayan Kumar
authors.initials: NK
authors.lastname: Mohanty
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins