Alpha 2-b interferon and farmarubicin in the prophylaxis of recurrence of superficial transitional cell carcinoma of the urinary bladder.
OBJECTIVE
To ascertain the effect of intravesical instillation of Alpha 2-b Interferon (IFN a-2) 10 million I.U. in 50 ml physiological saline as a monotherapy and in combination with Farmarubicin (FRC) 50 mg dissolved together in 50 ml of physiological saline. These substances were administered four times during the first month after TUR-BT and then once monthly for one year either in the form of an IFN a-2 monotherapy or as an IFN a-2 and FRC combination in the therapy of recurrence of transitional cell carcinoma (TCC) of the urinary bladder after transurethral resection of the bladder tumor (TUR-BT). THEORETICAL CONSIDERATION: One of the causes of malignancy is an irreversible shift in the balance between protooncogens and tumor supressorgens. In the genetical process of the control of cell apoptosis, an important role is played by the tumor-supressorgen p 53. By the means of mutation of protooncogenes, cellular oncogenes(C-MYC) are formed, inducing the proliferation of cells of the tumor and via feedback induce also the p53 mutation. By the reduction of cellular oncogenes, IFN a-2 and FRC intervene by blocking the proliferation of tumor cells.


METHODS
Authors have checked and treated 33 patients (pts) with recurrent TCC. The first group of 20 pts were after TUR-BT with BCG unsuccessful intravesical therapy, and 13 pts in the second group were with recurrence of TCC, but contraindicated for BCG treatment. These 33 pts (the first and second groups) were compared with 33 pts of the third group after TUR-BT but without intravesical instillation therapy. The pts of the third group did not suffer from any other significant ailment. IFN a-2 monotherapy (10 mill. I.U./or a combination of IFN a-2 + FRC (50 mg/50 ml solution were administered for 2 hours, 1 week after TUR-BT. During the first month, instillations were done weekly, from the second to the twelfth month only once monthly. The results were evaluated for 12 to 33 months (median: 24 months).


RESULTS
Group I: From 20 pts after TUR-BT + unsuccessful BCG + IFN a-2 monotherapy recurrence was registered in 4 pts (20%). Group II: Out of 13 pts after TUR-BT + IFN a-2 + FRC, recurrence was registered in 3 pts (23%). Group I + II: Recurrence in both groups was observed in 7 pts (21.2%). Group III: Out of 33 pts after TUR-BT without immuno- et chemotherapy recurrence was registered in 18 pts (54.5%). After one year of treatment, patients were checked for 24 months. The transition into an invasive tumor was observed in 4 pts (12.1%). In the comparative group of 33 pts without instillation after TUR-BT, recurrence was detected after one year in 18 pts (54.5%) and the transition into an invasive tumor was observed in 7 pts (21.2%).


CONCLUSIONS
Intravesical instillation of BCG used to be the most frequently applied therapy following TUR-BT. The toxicity of this vaccine as well as the contraindication of this treatment in some diseases, and also the primary or secondary resistance of TCC to BCG have challenged the search for alternative possibilities of the intravesical instillation treatment. IFN a-2 monotherapy and IFN a-2 in combination with FRC are new alternative approaches in the improvement of TCC treatment. This therapy is also supported by research of molecular genetics. (Ref.18.)
Cervenakov
I
I
Department of Urology and Andrology, University Hospital, Bratislava, Slovakia.
Szoldova
K
K
Mardiak
J
J
Chovan
D
D
Mala
M
M
Slavov
D
D
D000283:Administration, Intravesical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000601:surgery*; D015251:Epirubicin / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011994:Recombinant Proteins; D001749:Urinary Bladder Neoplasms / Q000601:surgery*
D000903:Antibiotics, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015251:Epirubicin