The effectiveness of combined intravesical BCG+Interferon-alfa 2b in patients with superficial bladder cancer in whom BCG alone previously failed and the relationship with tumor p53 and serum anti-p53 antibodies

Objective: Our aim is to determine the effectiveness of combined low dose BCG and interferon-alfa 2b (IFN-alfa 2b) in patients, in whom BCG previously failed, and also the importance of tumor p53 expression and serum p53 antibodies on follow-up.

Materials and Methods: Between September 1999 and November 2003, 10 patients ages between 51-74 years (median 63) who previously failed intravesical BCG treatment are included in this study. These patients were undertaken to transurethral tumor resection and they were given 27 mg’s of Connaught BCG (1/3 dose) and 50 million units of IFN-2b once a week for 6 weeks. Serum anti-p53 abs were detected by enzyme linked immunosorbent assay (ELISA). During subsequent evaluation, each specimen in its entirety was examined with accepted positive cut-off criteria of 20% nuclear stainig. Median follow-up was 41 (32-50 months) months.

Results: 7 of 10 patients (70%) had no tumor recurrence and 3 had recurrence during follow-up. Patients with recurrences in cystoscopic controls were treated with transuretral resection (TUR-BT) and no additional intracavitary chemotherapy given these patients. No stage and grade progression was observed. This combination therapy is tolerated well by all patients and no side effects were observed. Three patients (30%) had positive tissue p53 and one of these patients (10%) had positive serum anti-p53 antibody. Both tumor p53 protein and serum anti-p53 protein were positive in one of the patients with recurrence.

Conclusions: The results of combined intravesical BCG and IFN-alfa 2b immunotherapy for superficial bladder cancer, in whom BCG previously failed, were encouraging. Tumor p53 and serum anti p-53 antibody positivity were not seen as a indicator of progression in these limited number of patient with long term follow-up.

BCG baþarýsýz yüzeyel mesane tümörlü olgularda kombine intravesikal BCG+Ýnterferon-alfa 2b tedavisinin etkinliði ve tümör p53 protein ve serum p53 antikorlar ile iliþkisi

Amaç: BCG baþarýsýz yüzeyel mesane tümörlü olgularda, ikinci basamak tedavisi olarak kullanýlacak olan düþiik doz BCG ve interferon-alfa 2b (IFN-2b) kombine tedavisinin rekürrens ve progresyon üzerine etkinliðini saptamanýn yaný sýra takipte tümör p53 ekspresyonu ve serum p53 antikorlarýnýn önemi incelendi.

Hastalar ve yöntem: BCG baþarýsýz 10 transizyonel hücreli karsinomlu (TCC) yüzeyel mesane tümörlü hasta, prospektif olarak çalýþmaya alýndý. Hastalara transüretral tümör rezeksiyonu sonrasý 6 hafta intravezikal 27 mg Coýmaught BCG (113 doz) ve 50 milyon ünite IFN-alfa 2b uygulandý. Hastalarda serum anti-p53 antikor ELISA yöntemi ile ve tümör p53 ekspresyonu immünohistokimyasal yöntemle saptandý. Ortalama takip 41 (32-50) ay idi.

Bulgular: Takip süresince 10 hastanýn 7 (%70)’sinde nüks izlenmezken, 3 hastada niiks saptandý. Hiçbir hastada evre ve grade progresyonu izlenmedi. Tüm hastalar tedaviyi iyi tolere ettiler ve hiçbir hastada yan etki gözlenmedi. 3 hastada doku p53 pozitif (%30) ve hu 3 hastanýn birinde de (%10) serum anti-p53 antikor pozitif bulundu. Rekürrens görülen bir hastada hem tümör p53 protein, hem de serum anti-p53 antikor pozitifliði saptandý.

Sonuçlar: BCG baþarýsýz yüzeyel mesane tümörlü hastalarda kombine intravezikal immünoterap‘ý cesaret verici olarak görülmektedir. Bu sýnýrlý olgu grubunda uzun dönem takip sonuçlarýna göre tümör p53 protein ve serum p53 antikor pozitifliði bir progresyon göstergesi olarak görülmedi.