- Email: [email protected]
Re: Fabio Calabrò and Cora N. Sternberg. Current Indications for Chemotherapy in Prostate Cancer Patients. Eur Urol 2007;51:17–26
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european urology 52 (2007) 611–614
Re: Stephen J. Bromage, Debbie A. Falconer, Brian A. Lieberman, et al. Sperm Retrieval Rates in Subgroups of Primary Azoospermic Males. Eur Urol 2007;51:534–40
decreased significantly with increasing levels of serum FSH.
We read with interest the paper on surgical sperm retrieval (SSR) in azoospermic men by Bromage et al [1]. We recently reported the outcome in 122 men attending the Oxford Fertility Unit with azoospermia in at least two general laboratory analyses [2]. We showed that sperm was present in the ejaculate of 22% of ‘‘azoospermic’’ men when using centrifugation techniques and a thorough microscopic search (extended sperm preparation [ESP]). Identified sperm was cryopreserved and used for subsequent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. The likelihood of finding sperm in the ejaculate was 5% in men with a history of vasectomy reversal and 30% in men with no clinical evidence of obstruction regardless of the serum follicle-stimulating hormone (FSH) concentration. Consequently, ESP should be considered before performing SSR for men with no obvious obstructive cause of their azoospermia. Similar to Bromage et al, we identified sperm on SSR in 32% of men with elevated FSH levels >10 IU/l. The likelihood of retrieving sperm
[1] Bromage SJ, Falconer DA, Lieberman BA, Sangar V, Payne SR. Sperm retrieval rates in subgroups of primary azoospermic males. Eur Urol 2007;51:534–40. [2] Swanton A, Itani A, McVeigh E, Child T. Azoospermia: is sample centrifugation indicated? A national survey of practice and the Oxford experience. Fertil Steril. In press. 2007. Epub ahead of print. Alexander Swanton* Tim Child 1 Oxford Fertility Unit, Level 4 Women’s Centre, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
References
*Corresponding author. Tel. +44 (0) 1865 220180; Fax: +44 (0) 1865 221031. E-mail addresses: [email protected] (A. Swanton) [email protected] (T. Child) 1
March 16, 2007 Published online ahead of print on March 26, 2007 doi:10.1016/j.eururo.2007.03.049
DOI of original article: 10.1016/j.eururo.2006.08.032
Re: Fabio Calabro` and Cora N. Sternberg. Current Indications for Chemotherapy in Prostate Cancer Patients. Eur Urol 2007;51:17–26 In their very interesting review article, Calabro` and Sternberg discuss the timing and selection of patients to treat for hormone-refractory prostate cancer (HRPC), giving a comprehensive overview of ongoing trials in first- and second-line settings [1]. The authors appropriately conclude that from the results of these ongoing studies, we will better define the future scenario of HRPC management. In the last couple of months, just after the cited review, some new data were released, which we believe deserve the attention of the whole urooncology community. 1. At the Prostate Cancer Symposium, a joint meeting of the American Society of Clinical Oncology, Society of Urologic Oncology, and American Society for Therapeutic Radiology and Oncology, held in February 2007 in Orlando, Florida, the final progression-free survival (PFS) results from the Satraplatin and Prednisone
Against Refractory Cancer (SPARC) trial, a doubleblind phase 3 trial, correctly highlighted by Sternberg and Calabro`, were presented [2]. These data, analyzed by a protocol-specified log-rank test, clearly show that treatment with satraplatin significantly reduces the risk of disease progression in these patients. Safety findings were consistent with previous clinical studies involving satraplatin. Satraplatin could be the first drug approved for patients with HRPC in whom prior therapies have failed. 2. In the same month, results of the Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT) trial, comparing docetaxel in combination with either DN-101 (high concentration formulation of calcitriol) or placebo in 250 patients with HRPC, were published in the Journal of Clinical Oncology [3]. The primary end point of the ASCENT trial was to evaluate the proportion of patients achieving a prostate-specific antigen (PSA) response. A >50% PSA decline was reached in 49% of placebotreated patients and 58% of patients treated with DN-101 ( p = 0.16). At any time while on this
614
european urology 52 (2007) 611–614
study, the PSA end point was reached in 52% of placebo patients and 63% of DN-101–treated patients ( p = 0.07). Median duration of PSA progression-free survival was similar in placebo and DN-101 groups as well as tumor response by Response Evaluation Criteria Solid Tumours (RECIST) criteria. Although the median survival in the placebo group was 16.4 mo, it has been estimated to be 24.5 mo in the DN-101 group. No increased toxicity was noted by the addition of DN-101 to docetaxel. 3. Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase 3 study was undertaken to evaluate its safety and efficacy in a placebo-controlled study. A total of 127 patients with asymptomatic HRPC were randomly assigned to receive three infusions of sipuleucel-T or placebo every 2 wk. A total of 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 mo. The median for time to disease progression for sipuleucel-T was 11.7 wk compared with 10.0 wk for placebo ( p = 0.052). Median survival was 25.9 mo for sipuleucel-T and 21.4 mo for placebo ( p = 0.01). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using multivariable regression model [4]. 4. At the mentioned Prostate Cancer Symposium, Sternberg herself announced preliminary results from a phase 2 study of Genasense (oblimersen sodium) injection plus chemotherapy in patients with HRPC. This randomized open-label trial was conducted by the European Organization for Research and Treatment of Cancer. Of 111 evaluable patients at baseline, >90% had widely metastatic disease to bone or viscera or both. Following randomization, patients were treated with docetaxel either with or without Genasense. For patients who received Genasense plus docetaxel versus docetaxel alone, response rates were similar as measured by RECIST criteria in patients with measurable disease (24% vs. 19%) or by PSA (37% vs. 46%). Neither progression-free nor overall survival has yet been reported. Occurrence of grade 3–4 neutropenia and febrile DOI of original article: 10.1016/j.eururo.2006.08.013
neutropenia was similar, whereas Genasense was associated with an increase in grade 3 thrombocytopenia. All these findings show that the ‘‘new era’’ for HRPC patients has just begun. Many efforts from investigators worldwide will clarify the optimum strategy for these patients and the most appropriate timing for their treatment. Future approaches will be mostly directed at finding out how to deal with (expected) failures of the (now) standard docetaxelbased therapy. In this setting, two main aims should be considered: to improve the survival and to preserve patients’ quality of life.
References [1] Calabro` F, Sternberg CN. Current indications for chemotherapy in prostate cancer patients. Eur Urol 2007; 51:17–26. [2] www.asco.org. Prostate Cancer Symposium 2007, 22–24 February, Orlando FL, USA. [3] Beer TM, Ryan CW, Venner PM, et al. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgenindependent prostate cancer: a report from the ASCENT investigators. J Clin Oncol 2007;25:669–74. [4] Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006;24:3089–94. Giuseppe Di Lorenzo* Cattedra di Oncologia Medica, Dip. di Endocrinologia e Oncologia Molecolare e Clinica, Universita` degli Studi Federico II, Napoli, Italy Riccardo Autorino Clinica Urologica, Seconda Universita` degli Studi, Napoli, Italy *Corresponding author E-mail address: [email protected] (G. Di Lorenzo) March 27, 2007 Published online ahead of print on April 3, 2007 doi:10.1016/j.eururo.2007.03.071
european urology 52 (2007) 611–614
Re: Stephen J. Bromage, Debbie A. Falconer, Brian A. Lieberman, et al. Sperm Retrieval Rates in Subgroups of Primary Azoospermic Males. Eur Urol 2007;51:534–40
decreased significantly with increasing levels of serum FSH.
We read with interest the paper on surgical sperm retrieval (SSR) in azoospermic men by Bromage et al [1]. We recently reported the outcome in 122 men attending the Oxford Fertility Unit with azoospermia in at least two general laboratory analyses [2]. We showed that sperm was present in the ejaculate of 22% of ‘‘azoospermic’’ men when using centrifugation techniques and a thorough microscopic search (extended sperm preparation [ESP]). Identified sperm was cryopreserved and used for subsequent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. The likelihood of finding sperm in the ejaculate was 5% in men with a history of vasectomy reversal and 30% in men with no clinical evidence of obstruction regardless of the serum follicle-stimulating hormone (FSH) concentration. Consequently, ESP should be considered before performing SSR for men with no obvious obstructive cause of their azoospermia. Similar to Bromage et al, we identified sperm on SSR in 32% of men with elevated FSH levels >10 IU/l. The likelihood of retrieving sperm
[1] Bromage SJ, Falconer DA, Lieberman BA, Sangar V, Payne SR. Sperm retrieval rates in subgroups of primary azoospermic males. Eur Urol 2007;51:534–40. [2] Swanton A, Itani A, McVeigh E, Child T. Azoospermia: is sample centrifugation indicated? A national survey of practice and the Oxford experience. Fertil Steril. In press. 2007. Epub ahead of print. Alexander Swanton* Tim Child 1 Oxford Fertility Unit, Level 4 Women’s Centre, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
References
*Corresponding author. Tel. +44 (0) 1865 220180; Fax: +44 (0) 1865 221031. E-mail addresses: [email protected] (A. Swanton) [email protected] (T. Child) 1
March 16, 2007 Published online ahead of print on March 26, 2007 doi:10.1016/j.eururo.2007.03.049
DOI of original article: 10.1016/j.eururo.2006.08.032
Re: Fabio Calabro` and Cora N. Sternberg. Current Indications for Chemotherapy in Prostate Cancer Patients. Eur Urol 2007;51:17–26 In their very interesting review article, Calabro` and Sternberg discuss the timing and selection of patients to treat for hormone-refractory prostate cancer (HRPC), giving a comprehensive overview of ongoing trials in first- and second-line settings [1]. The authors appropriately conclude that from the results of these ongoing studies, we will better define the future scenario of HRPC management. In the last couple of months, just after the cited review, some new data were released, which we believe deserve the attention of the whole urooncology community. 1. At the Prostate Cancer Symposium, a joint meeting of the American Society of Clinical Oncology, Society of Urologic Oncology, and American Society for Therapeutic Radiology and Oncology, held in February 2007 in Orlando, Florida, the final progression-free survival (PFS) results from the Satraplatin and Prednisone
Against Refractory Cancer (SPARC) trial, a doubleblind phase 3 trial, correctly highlighted by Sternberg and Calabro`, were presented [2]. These data, analyzed by a protocol-specified log-rank test, clearly show that treatment with satraplatin significantly reduces the risk of disease progression in these patients. Safety findings were consistent with previous clinical studies involving satraplatin. Satraplatin could be the first drug approved for patients with HRPC in whom prior therapies have failed. 2. In the same month, results of the Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT) trial, comparing docetaxel in combination with either DN-101 (high concentration formulation of calcitriol) or placebo in 250 patients with HRPC, were published in the Journal of Clinical Oncology [3]. The primary end point of the ASCENT trial was to evaluate the proportion of patients achieving a prostate-specific antigen (PSA) response. A >50% PSA decline was reached in 49% of placebotreated patients and 58% of patients treated with DN-101 ( p = 0.16). At any time while on this
614
european urology 52 (2007) 611–614
study, the PSA end point was reached in 52% of placebo patients and 63% of DN-101–treated patients ( p = 0.07). Median duration of PSA progression-free survival was similar in placebo and DN-101 groups as well as tumor response by Response Evaluation Criteria Solid Tumours (RECIST) criteria. Although the median survival in the placebo group was 16.4 mo, it has been estimated to be 24.5 mo in the DN-101 group. No increased toxicity was noted by the addition of DN-101 to docetaxel. 3. Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase 3 study was undertaken to evaluate its safety and efficacy in a placebo-controlled study. A total of 127 patients with asymptomatic HRPC were randomly assigned to receive three infusions of sipuleucel-T or placebo every 2 wk. A total of 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 mo. The median for time to disease progression for sipuleucel-T was 11.7 wk compared with 10.0 wk for placebo ( p = 0.052). Median survival was 25.9 mo for sipuleucel-T and 21.4 mo for placebo ( p = 0.01). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using multivariable regression model [4]. 4. At the mentioned Prostate Cancer Symposium, Sternberg herself announced preliminary results from a phase 2 study of Genasense (oblimersen sodium) injection plus chemotherapy in patients with HRPC. This randomized open-label trial was conducted by the European Organization for Research and Treatment of Cancer. Of 111 evaluable patients at baseline, >90% had widely metastatic disease to bone or viscera or both. Following randomization, patients were treated with docetaxel either with or without Genasense. For patients who received Genasense plus docetaxel versus docetaxel alone, response rates were similar as measured by RECIST criteria in patients with measurable disease (24% vs. 19%) or by PSA (37% vs. 46%). Neither progression-free nor overall survival has yet been reported. Occurrence of grade 3–4 neutropenia and febrile DOI of original article: 10.1016/j.eururo.2006.08.013
neutropenia was similar, whereas Genasense was associated with an increase in grade 3 thrombocytopenia. All these findings show that the ‘‘new era’’ for HRPC patients has just begun. Many efforts from investigators worldwide will clarify the optimum strategy for these patients and the most appropriate timing for their treatment. Future approaches will be mostly directed at finding out how to deal with (expected) failures of the (now) standard docetaxelbased therapy. In this setting, two main aims should be considered: to improve the survival and to preserve patients’ quality of life.
References [1] Calabro` F, Sternberg CN. Current indications for chemotherapy in prostate cancer patients. Eur Urol 2007; 51:17–26. [2] www.asco.org. Prostate Cancer Symposium 2007, 22–24 February, Orlando FL, USA. [3] Beer TM, Ryan CW, Venner PM, et al. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgenindependent prostate cancer: a report from the ASCENT investigators. J Clin Oncol 2007;25:669–74. [4] Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006;24:3089–94. Giuseppe Di Lorenzo* Cattedra di Oncologia Medica, Dip. di Endocrinologia e Oncologia Molecolare e Clinica, Universita` degli Studi Federico II, Napoli, Italy Riccardo Autorino Clinica Urologica, Seconda Universita` degli Studi, Napoli, Italy *Corresponding author E-mail address: [email protected] (G. Di Lorenzo) March 27, 2007 Published online ahead of print on April 3, 2007 doi:10.1016/j.eururo.2007.03.071