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1705 SYSTEMIC CHEMOTHERAPY REGIMEN INFLUENCES OUTCOME IN ADVANCED BLADDER CANCER
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THE JOURNAL OF UROLOGY姞
ing NAC and 43% of those with RC, alone (p⫽.29). In multivariate analyses, patients ⱖ75 years receiving NAC (n⫽24), were 3 times more likely to suffer a complication than those treated with RC, alone (n⫽42) [OR 3.0 (95% CI: 1.2,7.5) p⫽.038]; however, elder patients did not have a higher risk of severe complications [OR 1.66 (95% CI: 0.50,5.49) p⫽.44]. CONCLUSIONS: Neoadjuvant chemotherapy is a safe strategy for middle-aged patients undergoing RC; however, this treatment strategy has a much higher risk of perioperative complication in elder patients. Providers should consider this increased complication risk in patients over 75 years of age when planning treatment strategies and counsel individual patients appropriately. Source of Funding: Institutional Funding
1704 SEQUENTIAL CHEMOTHERAPY FOR ADVANCED BLADDER CANCER WITH CREATININE CLEARANCE 60 ML/MIN OR BELOW. Takahiro Yoneyama*, Kengo Imanishi, Teppei Okamoto, Naoki Sugiyama, Yuuichirou Suzuki, Shingo Hatakeyama, Shigemasa Kudo, Kazuyuki Mori, Yasuhiro Hashimoto, Takuya Koie, Noritaka Kamimura, Chikara Ohyama, Hirosaki, Japan INTRODUCTION AND OBJECTIVES: The standard chemotherapy for advanced bladder cancer is cisplatin-based. However, cisplatin is proved to be too toxic for the patients with impaired renal function. We retrospectively evaluated the feasibility and effectiveness of a sequential chemotherapy for the patients with advanced bladder cancer whose creatinine clearance (Ccr) was 60 ml/min or below. METHODS: The subjects were 29 patients with advanced bladder cancer (21 men and 8 women) whose Ccr were 60 ml/min or below. They were treated at our clinic between September 2004 and April 2009. Their average age was 68.9 years old (43-83), average Ccr of 41.8 ml/min (14.5-58.0), and an average follow-up period of 14.0 months (2-55). There were 14 recurrent cases after radical surgery and 15 inoperable cases (T4b or metastatic). As for prior chemotherapy, 6 underwent MVAC therapy. The therapeutic regimen consisted of three lines: gemcitabine/carboplatin (GC) therapy as the first line, with two courses as a set; GC/docetaxel (GCD) therapy as the second line if the response in the first line was insufficient; and finally as the third line, docetaxel/ifosfamide/nedaplatin (DIN) therapy if the GCD therapy was not sufficient. GC consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GC was performed. If this regimen did not induce any tumor size reduction, we switched to GCD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin(AUC 3) on day 2. DIN consisted of 75mg/m2 docetaxel on day 1, 2g/m2 ifosfamide on day 1 though day 3, and 100mg/m2 nedaplatin on day 2. RESULTS: Of the 29 subjects who had undergone the GC therapy, the response rate was 44.8% (CR⫹PR) with 4 and 9 subjects exhibiting a complete response (CR) and a partial response (PR), respectively; the average response duration was 8.6 months (3-27). Of the subjects with MVAC resistance, 1 exhibited a CR and 2 showed a PR. The response rates of 7 instances of GCD and 5 instances of DIN were 14.3% and 20.0%, respectively; the overall median survival was 13.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 21 of those who had undergone the GC therapy (72.4%). Bone marrow suppression was observed in 21 subjects (72.4%), whereas only 2 (6.9%) developed digestive symptoms. No subjects experienced the deterioration of their renal functions. CONCLUSIONS: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced bladder cancer with impaired renal function. Source of Funding: None
Vol. 183, No. 4, Supplement, Tuesday, June 1, 2010
1705 SYSTEMIC CHEMOTHERAPY REGIMEN INFLUENCES OUTCOME IN ADVANCED BLADDER CANCER Matthew Wosnitzer*, Gregory Hruby, LaMont Barlow, Mitchell Benson, Carlos Cordon-Cardo, Daniel Petrylak, James McKiernan, New York, NY INTRODUCTION AND OBJECTIVES: Treatment of locally advanced bladder cancer may include a variety of chemotherapy options. In 2000, a multicenter randomized phase III trial described that gemcitabine and cisplatin (GC) provide similar overall survival and response rate advantage to MVAC with better safety and tolerability profile in locally advanced (T4b, N2, N3) or metastatic patients. Since that time, GC has often replaced MVAC as the default treatment for advanced bladder cancer in the neoadjuvant and adjuvant settings without adequate evidence. We postulate that overall (OS) and disease-specific survival (DSS) are different between MVAC and GC in the neoadjuvant and adjuvant settings. METHODS: A retrospective review of the IRB-approved Comprehensive Columbia Urologic database identified 188 patients treated with systemic chemotherapy for T2-T4, N0-N2, M0 or metastatic bladder cancer from January 1988 through July 2009. Patients receiving induction or salvage systemic chemotherapy were excluded. RESULTS: Of 188 patients treated with systemic chemotherapy for bladder cancer, 122 patients received cisplatin-based regimens in the neoadjuvant or adjuvant setting (62 and 60 respectively) for T2-T4a, N0-N3, M0 bladder cancer. 79 received MVAC and 43 received GC. Pathologic complete response rates from cystectomy (or cystoscopy in those refusing cystectomy) following neoadjuvant chemotherapy was 30% (n⫽13/43) in the MVAC group and 16% (n⫽3/19) in the GC group (p⫽.231). In all patients receiving neoadjuvant and adjuvant chemotherapy, GC was associated with significantly decreased OS (p⫽.032, HR 2.09, CI 1.05-4.17) while this difference was not seen in DSS (p⫽.255). In the adjuvant setting, GC regimen had significantly worse OS and DSS rates than MVAC in univariate and multivariate analysis (p⫽.009, HR 5.68, CI 1.53-20.99). In the neoadjuvant setting, there was a trend toward worse OS with GC compared with MVAC (p⫽.052, HR 3.6, CI 0.99-13.5), but there was no difference in DSS with GC compared with MVAC (p⫽.297). CONCLUSIONS: Despite lack of evidence, GC and MVAC regimens have been used interchangeably in the treatment of advanced bladder cancer with assumed equivalency. In our study of patients from the past two decades, GC used in the adjuvant chemotherapy setting is associated with and is an independent predictor of decreased OS and DSS when compared with MVAC. There is a trend for this finding in the neoadjuvant setting with MVAC. MVAC appears to be the more effective chemotherapy regimen for those patients who can tolerate the side effects in the perioperative setting. Source of Funding: None
1706 CARBOPLATIN VS. CISPLATIN-BASED CHEMOTHERAPY IN THE PERIOPERATIVE TREATMENT OF MUSCLE-INVASIVE BLADDER CANCER Matthew Wosnitzer*, Gregory Hruby, Carlos Cordon-Cardo, Mitchell Benson, Daniel Petrylak, James McKiernan, New York, NY INTRODUCTION AND OBJECTIVES: Treatment of locally advanced bladder cancer may include methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), gemcitabine and cisplatin (GC), and gemcitabine and carboplatin (GCarbo). These options have varying effects on toxicity and efficacy. In phase II studies, carboplatin is active and tolerable with reduced risk of renal, auditory, and neurologic toxicities but with varying response rates (20-70%) when compared to cisplatin. To our knowledge, few studies have assessed the efficacy of carboplatin regimens with cisplatin regimens in urothelial carcinoma. METHODS: The IRB approved database identified 188 patients treated with systemic chemotherapy for any indication (neoadjuvant,
THE JOURNAL OF UROLOGY姞
ing NAC and 43% of those with RC, alone (p⫽.29). In multivariate analyses, patients ⱖ75 years receiving NAC (n⫽24), were 3 times more likely to suffer a complication than those treated with RC, alone (n⫽42) [OR 3.0 (95% CI: 1.2,7.5) p⫽.038]; however, elder patients did not have a higher risk of severe complications [OR 1.66 (95% CI: 0.50,5.49) p⫽.44]. CONCLUSIONS: Neoadjuvant chemotherapy is a safe strategy for middle-aged patients undergoing RC; however, this treatment strategy has a much higher risk of perioperative complication in elder patients. Providers should consider this increased complication risk in patients over 75 years of age when planning treatment strategies and counsel individual patients appropriately. Source of Funding: Institutional Funding
1704 SEQUENTIAL CHEMOTHERAPY FOR ADVANCED BLADDER CANCER WITH CREATININE CLEARANCE 60 ML/MIN OR BELOW. Takahiro Yoneyama*, Kengo Imanishi, Teppei Okamoto, Naoki Sugiyama, Yuuichirou Suzuki, Shingo Hatakeyama, Shigemasa Kudo, Kazuyuki Mori, Yasuhiro Hashimoto, Takuya Koie, Noritaka Kamimura, Chikara Ohyama, Hirosaki, Japan INTRODUCTION AND OBJECTIVES: The standard chemotherapy for advanced bladder cancer is cisplatin-based. However, cisplatin is proved to be too toxic for the patients with impaired renal function. We retrospectively evaluated the feasibility and effectiveness of a sequential chemotherapy for the patients with advanced bladder cancer whose creatinine clearance (Ccr) was 60 ml/min or below. METHODS: The subjects were 29 patients with advanced bladder cancer (21 men and 8 women) whose Ccr were 60 ml/min or below. They were treated at our clinic between September 2004 and April 2009. Their average age was 68.9 years old (43-83), average Ccr of 41.8 ml/min (14.5-58.0), and an average follow-up period of 14.0 months (2-55). There were 14 recurrent cases after radical surgery and 15 inoperable cases (T4b or metastatic). As for prior chemotherapy, 6 underwent MVAC therapy. The therapeutic regimen consisted of three lines: gemcitabine/carboplatin (GC) therapy as the first line, with two courses as a set; GC/docetaxel (GCD) therapy as the second line if the response in the first line was insufficient; and finally as the third line, docetaxel/ifosfamide/nedaplatin (DIN) therapy if the GCD therapy was not sufficient. GC consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GC was performed. If this regimen did not induce any tumor size reduction, we switched to GCD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin(AUC 3) on day 2. DIN consisted of 75mg/m2 docetaxel on day 1, 2g/m2 ifosfamide on day 1 though day 3, and 100mg/m2 nedaplatin on day 2. RESULTS: Of the 29 subjects who had undergone the GC therapy, the response rate was 44.8% (CR⫹PR) with 4 and 9 subjects exhibiting a complete response (CR) and a partial response (PR), respectively; the average response duration was 8.6 months (3-27). Of the subjects with MVAC resistance, 1 exhibited a CR and 2 showed a PR. The response rates of 7 instances of GCD and 5 instances of DIN were 14.3% and 20.0%, respectively; the overall median survival was 13.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 21 of those who had undergone the GC therapy (72.4%). Bone marrow suppression was observed in 21 subjects (72.4%), whereas only 2 (6.9%) developed digestive symptoms. No subjects experienced the deterioration of their renal functions. CONCLUSIONS: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced bladder cancer with impaired renal function. Source of Funding: None
Vol. 183, No. 4, Supplement, Tuesday, June 1, 2010
1705 SYSTEMIC CHEMOTHERAPY REGIMEN INFLUENCES OUTCOME IN ADVANCED BLADDER CANCER Matthew Wosnitzer*, Gregory Hruby, LaMont Barlow, Mitchell Benson, Carlos Cordon-Cardo, Daniel Petrylak, James McKiernan, New York, NY INTRODUCTION AND OBJECTIVES: Treatment of locally advanced bladder cancer may include a variety of chemotherapy options. In 2000, a multicenter randomized phase III trial described that gemcitabine and cisplatin (GC) provide similar overall survival and response rate advantage to MVAC with better safety and tolerability profile in locally advanced (T4b, N2, N3) or metastatic patients. Since that time, GC has often replaced MVAC as the default treatment for advanced bladder cancer in the neoadjuvant and adjuvant settings without adequate evidence. We postulate that overall (OS) and disease-specific survival (DSS) are different between MVAC and GC in the neoadjuvant and adjuvant settings. METHODS: A retrospective review of the IRB-approved Comprehensive Columbia Urologic database identified 188 patients treated with systemic chemotherapy for T2-T4, N0-N2, M0 or metastatic bladder cancer from January 1988 through July 2009. Patients receiving induction or salvage systemic chemotherapy were excluded. RESULTS: Of 188 patients treated with systemic chemotherapy for bladder cancer, 122 patients received cisplatin-based regimens in the neoadjuvant or adjuvant setting (62 and 60 respectively) for T2-T4a, N0-N3, M0 bladder cancer. 79 received MVAC and 43 received GC. Pathologic complete response rates from cystectomy (or cystoscopy in those refusing cystectomy) following neoadjuvant chemotherapy was 30% (n⫽13/43) in the MVAC group and 16% (n⫽3/19) in the GC group (p⫽.231). In all patients receiving neoadjuvant and adjuvant chemotherapy, GC was associated with significantly decreased OS (p⫽.032, HR 2.09, CI 1.05-4.17) while this difference was not seen in DSS (p⫽.255). In the adjuvant setting, GC regimen had significantly worse OS and DSS rates than MVAC in univariate and multivariate analysis (p⫽.009, HR 5.68, CI 1.53-20.99). In the neoadjuvant setting, there was a trend toward worse OS with GC compared with MVAC (p⫽.052, HR 3.6, CI 0.99-13.5), but there was no difference in DSS with GC compared with MVAC (p⫽.297). CONCLUSIONS: Despite lack of evidence, GC and MVAC regimens have been used interchangeably in the treatment of advanced bladder cancer with assumed equivalency. In our study of patients from the past two decades, GC used in the adjuvant chemotherapy setting is associated with and is an independent predictor of decreased OS and DSS when compared with MVAC. There is a trend for this finding in the neoadjuvant setting with MVAC. MVAC appears to be the more effective chemotherapy regimen for those patients who can tolerate the side effects in the perioperative setting. Source of Funding: None
1706 CARBOPLATIN VS. CISPLATIN-BASED CHEMOTHERAPY IN THE PERIOPERATIVE TREATMENT OF MUSCLE-INVASIVE BLADDER CANCER Matthew Wosnitzer*, Gregory Hruby, Carlos Cordon-Cardo, Mitchell Benson, Daniel Petrylak, James McKiernan, New York, NY INTRODUCTION AND OBJECTIVES: Treatment of locally advanced bladder cancer may include methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), gemcitabine and cisplatin (GC), and gemcitabine and carboplatin (GCarbo). These options have varying effects on toxicity and efficacy. In phase II studies, carboplatin is active and tolerable with reduced risk of renal, auditory, and neurologic toxicities but with varying response rates (20-70%) when compared to cisplatin. To our knowledge, few studies have assessed the efficacy of carboplatin regimens with cisplatin regimens in urothelial carcinoma. METHODS: The IRB approved database identified 188 patients treated with systemic chemotherapy for any indication (neoadjuvant,