This month we will be focusing on data from the recent 2009 Genitourinary Cancers Symposium. This meeting was held on February 26-28, 2009 in Orlando, FL and co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiology and Oncology (ASTRO), and the Society of Urologic Oncology (SUO). The following topics were presented as part of educational sessions along with oral abstract presentations.

Bladder Cancer

An educational symposium on new drugs and treatment strategies for bladder cancer was held. Dr Robert Dreicer from the Cleveland Clinic presented data on the targeted therapeutics for advanced urothelial cancer.⁶ He introduced the topic by stating that over the past 2 decades, 2 cisplatin-based chemotherapy regimens (methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC] and gemcitabine and cisplatin [GC]) have become the standard of care for front-line chemotherapy. However, there are many molecular targets that are being investigated in urothelial tumors that are of interest to medical oncologists.

The epidermal growth factor receptor (EGFR) is overexpressed in many high-grade urothelial tumors and is being investigated in combination with chemotherapy agents. Two separate gefitinib trials have failed to show an improvement in outcome.

Combined HER-1 and HER-2 expression has been reported in up to one-third of bladder cancers, however 1 reported clinical trial with lapatinib had a very low response rate (1/59).

HER-2 has been variably overexpressed in bladder cancer. The response rates of adding trastuzumab to platinum-based chemotherapy has been high, but it is difficult to understand the contribution of the anti-HER-2 therapy. The further elucidate this benefit, there is an ongoing randomized phase II trial combining chemotherapy (GC) with or without trastuzumab in the front-line setting.

Finally, vascular endothelial growth factor (VEGF) seems to be a suitable target for urothelial cancers as well. An Eastern Cooperative Oncology Group (ECOG) trial with single-agent sorafenib in patients with disease progression following platinum-based chemotherapy failed to show any responses. Sunitinib has also been evaluated in this same clinical situation with 3 of 41 achieving a PR and 11 achieving stable disease. Sunitinib is also being explored in multiple other clinical settings for patients with urothelial malignancies. The Cancer and Leukemia Group B (CALGB) has proposed a randomized phase III trial comparing GC with GC + bevacizumab in patients with untreated metastatic urothelial malignancies based on promising phase II data with this combination.

We will await the results of these trials to understand the potential benefits and toxicities of adding targeted therapy to standard chemotherapy for patients with advanced urothelial cancer.

Two oral abstracts of interest were presented as part of the symposium.

Siefker-Radtke, et al from the M. D. Anderson Cancer Center presented an interesting clinical trial that incorporated response into the treatment decision-making.⁷ They performed a phase II randomized 4-regimen trial where patients were assigned to 1 of the following regimens: ifosfamide, doxorubicin, gemcitabine; ifosfamide, paclitaxel, cisplatin; gemcitabine, cisplatin; or gemcitabine, cisplatin, ifosfamide. Once a patient is randomized to their initial arm, they must have shown at least a 40% response after the first 6-week interval, and a >90% response after the second 6 weeks to continue on that arm. If they fail to achieve either of those benchmarks, then they are re-randomized to 1 of the remaining 3 arms. Overall success was defined as a >90% response with either front-line or second-line therapy. The results showed an overall survival (OS) for the 120 patients of 19.1 months. Overall success was seen in 41/120 patients, and their OS was 51 months. The median OS of the remaining patients was 15 months. Surgical consolidation in patients with overall success from their chemotherapy was associated with a 42% 5-year survival compared to an 11% 5-year survival in those who underwent surgery with less than the criteria for overall success. The authors concluded that with sequential therapy, 34% of patients had a >90% response rate. They suggested that this novel clinical trial design enhanced the population of patients who might be offered surgical consolidation in the setting of metastatic or unresectable urothelial cancer.

Apolo, et al from the Memorial-Sloan Kettering Cancer Center evaluating the clinical value of ¹⁸F-2-deoxyglucose positron emission tomography (FDG-PET) in bladder cancer, presented the second abstract.⁸ The study presented was performed to investigate the value of PET in initial staging as well as assessing treatment response and evaluating for recurrence. Fifty-seven bladder cancer patients under went PET for initial staging (n = 12), treatment response (n = 4), or for suspected recurrence (n = 41). Positron emission tomography correctly diagnosed malignant disease in 24/30 patients for a sensitivity of 80%. Positron emission tomography was negative in 15/16 patients without malignant lesions for a specificity of 94%. An organ-specific analysis was also performed. Positron emission tomography performed for suspected recurrence found more disease than determined by computed tomography (CT) or magnetic resonance imaging (MRI) in 49% of the cases. Clinicians changed their original planned management after PET results in 63% of cases, and felt that PET scan avoided more tests in 70% of cases. The authors concluded that FDG-PET had excellent sensitivity and specificity and provided additional diagnostic information over CT or MRI.

OncoFacts™ Editor:

Christy Russell , MD

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