Recent developments in advanced urothelial cancer.

PURPOSE OF REVIEW: Metastatic or unresectable urothelial cancer of the urinary bladder has traditionally been treated with systemic chemotherapy, which is most often platinum-based. The long-term survival data and the associated toxicities from this form of therapy have spurred continuing interest in finding novel treatment options for this malignancy. RECENT FINDINGS: Recently, trials of new chemotherapy combinations, many incorporating platinum analogs or deleting platinum entirely, have been reported. None has yet been shown to be superior to cisplatin-based regimens. In addition, recent advances in imaging and laboratory technologies have provided new avenues to understand urothelial cancer behavior and prognosis. These advances provide optimism for improvements in the diagnosis, staging, and ultimately, selection of therapy for patients with urothelial cancer. SUMMARY: This review will summarize recent developments (circa 2004) in the diagnosis and management of advanced bladder cancer.

Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial.

BACKGROUND: Overexpression of the HER-2/neu oncoprotein has been reported to occur in 2) were initially randomized to receive either single-agent trastuzumab or docetaxel. After two treatment cycles, nonresponding patients received the trastuzumab/docetaxel combination. Treatment was comprised of 30 mg/m(2) of docetaxel weekly for 6 weeks followed by a 2-week break and 4 mg/kg of trastuzumab intravenously during Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks. RESULTS: One hundred patients with HPRC were screened. IHC results were as follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed HER-2 by ELISA (> 15 mg/mL). None overexpressed HER-2 by IHC. FISH amplification was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score did not correlate with IHC status. Of the seven patients eligible for the Phase II study, only four agreed to participate. The trial was thus closed for nonfeasibility (the overall HER-2 positivity rate was < 20%). No patient responded to trastuzumab alone. The median survival was not reached and the median progression-free survival was 7 months. CONCLUSIONS: HER-2 overexpression by IHC in archival prostate carcinoma specimens was infrequent. There was no apparent correlation among IHC, ELISA, and FISH, although the sample size was limited. Conclusions regarding the predictive value of HER-2 status on outcome after trastuzumab-based therapy were not reached and were only drawn after larger-scale screening efforts. The authors estimated that 1000 patients need to be screened to complete accrual to a 40-patient efficacy trial.