- Email: [email protected]
Re: Phase II Trial of Sorafenib Plus Interferon Alfa-2b as First- or Second-Line Therapy in Patients with Metastatic Renal Cell Cancer
399
EUROPEAN UROLOGY 56 (2009) 395–400
[2] Swanson GP, et al. Predominant treatment failure in prostatectomy
Eduardo Solsona
patients is local: analysis of patterns of treatment failure in SWOG
Instituto Valenciano de Oncologı´a, Valencia, Spain
8794. J Clin Oncol 2007;25:2225–9.
E-mail address: [email protected]
[3] Coen JJ. Radical radiation for localized prostate cancer: local persistent of disease results in a late wave of metastasis. J Clin Oncol 2002;20:3199–205.
Re: Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome Nickel JC, Krieger JN, McNaughton-Collins M, et al N Engl J Med 2008;359:2663–73 Expert’s summary: This study is a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin in reducing symptoms in men with chronic prostatitis– chronic pelvic pain syndrome (CPPS). Treatment-naı¨ve men were randomly assigned to either 10 mg alfuzosin per day or placebo. The study duration was 12 wk. A total of 272 patients underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least four points in their total US National Institutes of Health Chronic Prostatitis Symptom Index score ( p = 0.99). Additionally, a global response assessment showed a similar response rate at 12 wk for 33.6% in the placebo group and 34.8% in the alfuzosin group ( p = 0.9). The rates of adverse events in the two groups were similar. This randomized controlled trial (RCT) does not support the use of alfuzosin to reduce CPPS in men who have not received prior treatment with an a-blocker.
DOI: 10.1016/j.eururo.2009.05.039
is a frequently recommended approach, based on a few small-sized randomized trials [4]. This RCT—the largest to date—published in the New England Journal of Medicine does not support the use of a-blockers for men with CPPS [4]. Consequently, this study should prompt reconsideration of the first-line therapy in men with CPPS. This negative RCT, together with several lines of recent scientific evidence, suggests that pathomechanisms outside the prostate play an important role in the pathogenesis of the CPPS [5]. Conflicts of interest: The author has nothing to disclose.
References [1] Marszalek M, Wehrberger C, Hochreiter W, Temml C, Madersbacher S. Symptoms suggestive of chronic pelvic pain syndrome in
an
urban population: prevalence and associations with lower urinary tract symptoms and erectile function. J Urol 2007;177: 1815–9. [2] Bartoletti R, Cai T, Mondaini N, et al. Italian Prostatitis Study Group. Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study. J Urol 2007;178:2411–5. [3] Alexander RB, Propert KJ, Schaeffer AJ, et al. Chronic Prostatits Collaborative Research Network. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome. Ann
Expert’s comments: CPPS belongs to the most frequent diseases in urology, with a prevalence in population-based surveys in the range of 3–10%, and affects around 15% of all urologic outpatients [1,2]. The management of patients suffering from CPPS is among the most challenging issues in outpatient urology, with frequent frustrations for both patients and treating physicians. A variety of therapeutic approaches have been proposed, the most frequent ones being a-receptor blockers, antibiotics, and antiphlogistics (triple-A therapy) used as monotherapy or in combination. Insufficient evidence supports this approach for patients who did not benefit from a previous therapeutic course with these agents [3]. For treatment-naı¨ve patients, however, the triple-A therapy
Re: Phase II Trial of Sorafenib Plus Interferon Alfa-2b as First- or Second-Line Therapy in Patients with Metastatic Renal Cell Cancer Gollob JA, Rathmell WK, Richmond TM, et al. J Clin Oncol 2007;25:3288–95
Intern Med 2004;141:581–9. [4] Nickel JC, Krieger JN, McNaughton-Collins M, et al. Chronic Prostatitis Collaborative Research Network. Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome. N Engl J Med 2008;359:2663–73. [5] Marszalek M, Wehrberger C, Temml C, Ponholzer A, Berger I, Madersbacher S. Chronic pelvic pain and lower urinary tract symptoms in both sexes: analysis of 2749 participants of an urban health screening project. Eur Urol 2009;55:499–508. Stephan Madersbacher Urology, Donauspital – SMZO, Wien, Austria E-mail addresses: [email protected], [email protected] DOI: 10.1016/j.eururo.2009.05.035
Expert’s summary: Forty patients were enrolled into a phase 2 trial of sorafenib plus interferon-a2b. The treatment consisted of eight cycles of sorafenib plus interferon-a2b three times a week. The response rate was 33%, including 28% with partial responses (n = 11) and 5% with complete responses (n = 2). Fatigue, anorexia, anemia, diarrhea, rash, and weight loss were
400
EUROPEAN UROLOGY 56 (2009) 395–400
common toxicities. Dose reductions were required in 65% of patients. The combination of sorafenib and interferon-a2b had substantial activity in treatment-naı¨ve patients and in patients with renal cell carcinoma (RCC) who were treated with interleukin 2. The toxicity exceeded that of either drug alone, but dose reductions allowed for chronic therapy. A larger randomized trial would determine whether this regimen has any advantage as opposed to sorafenib alone.
demonstrated that these two agents can be used safely, although toxicity was greater than anticipated with combined use of these drugs. Responses tended to occur rapidly. Although these newer agents do not cure patients, they do appear to prolong life. The evolution of multiple new molecular treatment agents represents a major rapid change in the treatment of RCC. Conflicts of interest: The author has nothing to disclose.
Expert’s comments: The genetic, molecular changes responsible for clear-cell RCC and other RCC cell types have been worked out in extraordinary detail by Dr. Linehan and his group at the US National Institutes of Health over many years [1]. Once the genetic, molecular mechanisms of the evolution of RCC were identified, particularly through the vascular endothelial growth factor (VEGF) pathway, then it became possible to affect these pathways. Treatment can then be initiated [2]. This paper is one of many that identifies sorafenib, a multikinase inhibitor that targets the VEGF receptors, platelet-derived growth factor b-receptor, and Raf kinase. All can affect the evolution of RCC. Interferon-a has a low treatment response rate in RCC [3]. In this study, sorafenib was combined with interferon-a, and the response rate was 33%, including partial and complete responses, with a median duration of 12 mo. This study
References [1] Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol 2003;170:2163–72. [2] Escudier B, Eisen T, Stadier GM, et al. TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;316: 125–34. [3] Negrier S, Escudier B, Lasset C, et al. Groupe Francais d’Immunotherapie. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 1998;338:1272–8. Fray F. Marshall Department of Urology, Emory University School of Medicine, Atlanta, GA, USA E-mail address: [email protected]
DOI: 10.1016/j.eururo.2009.05.036
EUROPEAN UROLOGY 56 (2009) 395–400
[2] Swanson GP, et al. Predominant treatment failure in prostatectomy
Eduardo Solsona
patients is local: analysis of patterns of treatment failure in SWOG
Instituto Valenciano de Oncologı´a, Valencia, Spain
8794. J Clin Oncol 2007;25:2225–9.
E-mail address: [email protected]
[3] Coen JJ. Radical radiation for localized prostate cancer: local persistent of disease results in a late wave of metastasis. J Clin Oncol 2002;20:3199–205.
Re: Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome Nickel JC, Krieger JN, McNaughton-Collins M, et al N Engl J Med 2008;359:2663–73 Expert’s summary: This study is a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin in reducing symptoms in men with chronic prostatitis– chronic pelvic pain syndrome (CPPS). Treatment-naı¨ve men were randomly assigned to either 10 mg alfuzosin per day or placebo. The study duration was 12 wk. A total of 272 patients underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least four points in their total US National Institutes of Health Chronic Prostatitis Symptom Index score ( p = 0.99). Additionally, a global response assessment showed a similar response rate at 12 wk for 33.6% in the placebo group and 34.8% in the alfuzosin group ( p = 0.9). The rates of adverse events in the two groups were similar. This randomized controlled trial (RCT) does not support the use of alfuzosin to reduce CPPS in men who have not received prior treatment with an a-blocker.
DOI: 10.1016/j.eururo.2009.05.039
is a frequently recommended approach, based on a few small-sized randomized trials [4]. This RCT—the largest to date—published in the New England Journal of Medicine does not support the use of a-blockers for men with CPPS [4]. Consequently, this study should prompt reconsideration of the first-line therapy in men with CPPS. This negative RCT, together with several lines of recent scientific evidence, suggests that pathomechanisms outside the prostate play an important role in the pathogenesis of the CPPS [5]. Conflicts of interest: The author has nothing to disclose.
References [1] Marszalek M, Wehrberger C, Hochreiter W, Temml C, Madersbacher S. Symptoms suggestive of chronic pelvic pain syndrome in
an
urban population: prevalence and associations with lower urinary tract symptoms and erectile function. J Urol 2007;177: 1815–9. [2] Bartoletti R, Cai T, Mondaini N, et al. Italian Prostatitis Study Group. Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study. J Urol 2007;178:2411–5. [3] Alexander RB, Propert KJ, Schaeffer AJ, et al. Chronic Prostatits Collaborative Research Network. Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome. Ann
Expert’s comments: CPPS belongs to the most frequent diseases in urology, with a prevalence in population-based surveys in the range of 3–10%, and affects around 15% of all urologic outpatients [1,2]. The management of patients suffering from CPPS is among the most challenging issues in outpatient urology, with frequent frustrations for both patients and treating physicians. A variety of therapeutic approaches have been proposed, the most frequent ones being a-receptor blockers, antibiotics, and antiphlogistics (triple-A therapy) used as monotherapy or in combination. Insufficient evidence supports this approach for patients who did not benefit from a previous therapeutic course with these agents [3]. For treatment-naı¨ve patients, however, the triple-A therapy
Re: Phase II Trial of Sorafenib Plus Interferon Alfa-2b as First- or Second-Line Therapy in Patients with Metastatic Renal Cell Cancer Gollob JA, Rathmell WK, Richmond TM, et al. J Clin Oncol 2007;25:3288–95
Intern Med 2004;141:581–9. [4] Nickel JC, Krieger JN, McNaughton-Collins M, et al. Chronic Prostatitis Collaborative Research Network. Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome. N Engl J Med 2008;359:2663–73. [5] Marszalek M, Wehrberger C, Temml C, Ponholzer A, Berger I, Madersbacher S. Chronic pelvic pain and lower urinary tract symptoms in both sexes: analysis of 2749 participants of an urban health screening project. Eur Urol 2009;55:499–508. Stephan Madersbacher Urology, Donauspital – SMZO, Wien, Austria E-mail addresses: [email protected], [email protected] DOI: 10.1016/j.eururo.2009.05.035
Expert’s summary: Forty patients were enrolled into a phase 2 trial of sorafenib plus interferon-a2b. The treatment consisted of eight cycles of sorafenib plus interferon-a2b three times a week. The response rate was 33%, including 28% with partial responses (n = 11) and 5% with complete responses (n = 2). Fatigue, anorexia, anemia, diarrhea, rash, and weight loss were
400
EUROPEAN UROLOGY 56 (2009) 395–400
common toxicities. Dose reductions were required in 65% of patients. The combination of sorafenib and interferon-a2b had substantial activity in treatment-naı¨ve patients and in patients with renal cell carcinoma (RCC) who were treated with interleukin 2. The toxicity exceeded that of either drug alone, but dose reductions allowed for chronic therapy. A larger randomized trial would determine whether this regimen has any advantage as opposed to sorafenib alone.
demonstrated that these two agents can be used safely, although toxicity was greater than anticipated with combined use of these drugs. Responses tended to occur rapidly. Although these newer agents do not cure patients, they do appear to prolong life. The evolution of multiple new molecular treatment agents represents a major rapid change in the treatment of RCC. Conflicts of interest: The author has nothing to disclose.
Expert’s comments: The genetic, molecular changes responsible for clear-cell RCC and other RCC cell types have been worked out in extraordinary detail by Dr. Linehan and his group at the US National Institutes of Health over many years [1]. Once the genetic, molecular mechanisms of the evolution of RCC were identified, particularly through the vascular endothelial growth factor (VEGF) pathway, then it became possible to affect these pathways. Treatment can then be initiated [2]. This paper is one of many that identifies sorafenib, a multikinase inhibitor that targets the VEGF receptors, platelet-derived growth factor b-receptor, and Raf kinase. All can affect the evolution of RCC. Interferon-a has a low treatment response rate in RCC [3]. In this study, sorafenib was combined with interferon-a, and the response rate was 33%, including partial and complete responses, with a median duration of 12 mo. This study
References [1] Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol 2003;170:2163–72. [2] Escudier B, Eisen T, Stadier GM, et al. TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;316: 125–34. [3] Negrier S, Escudier B, Lasset C, et al. Groupe Francais d’Immunotherapie. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 1998;338:1272–8. Fray F. Marshall Department of Urology, Emory University School of Medicine, Atlanta, GA, USA E-mail address: [email protected]
DOI: 10.1016/j.eururo.2009.05.036