Prostatic Neoplasms: Beuzeboc P

Soulie M, Beuzeboc P, Richaud P, Villers A, Kassab-Chahmi D, Bataillard A, Anonymous00082, Anonymous00083. · Comité rédacteur SOR, INCA, FNCLCC, La Ligue, FHF FNCHRU, FFC et AFU. · Prog Urol. · Pubmed #17633990 No free full text.

Abstract: This paper is based on the bulletin of synthesis 2005. Management of non metastatic prostate cancer. Recommendations for clinical practice of the French Urologial Association and the National Federation of Anticancer Centers.

Richaud P, Moreau JL, Beuzeboc P, Rébillard X, Villers A, Peyromaure M, Cornud F, Soulié M, Davin JL, Anonymous00194. · Comité Prostate du CCAFU. · Prog Urol. · Pubmed #16459666 No free full text.

Abstract: The follow-up of prostate cancer is especially justified now that effective treatment options are available in the case of recurrence. Conditions of follow-up of patients with prostate cancer vary according to age, comorbidities, tumour stage, prognostic factors at diagnosis and the pervious treatment sequence.

Soulié M, Barré C, Beuzeboc P, Chautard D, Cornud F, Eschwege P, Fontaine E, Molinié V, Moreau JL, Péneau M, Ravery V, Rébillard X, Richaud P, Ruffion A, Salomon L, Staerman F, Villers A, Anonymous00315. · No affiliation provided · Prog Urol. · Pubmed #15779654 No free full text.

This publication has no abstract.

Molinié V, Beuzeboc P, Mahjoub WK, Anonymous00083. · Service de pathologie, groupe hospitalier Paris-Saint-Joseph, 185, rue Raymond-Losserand, 75014 Paris, France. · Ann Pathol. · Pubmed #19068390 No free full text.

Abstract: The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the tumorigenesis of prostate cancer. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancers makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

Benchikh El Fegoun A, Villers A, Moreau JL, Richaud P, Rebillard X, Beuzeboc P. · Service d'urologie, hôpital Claude-Huriez, 2, avenue Oscar-Lambret, 59037 Lille cedex, France. · Prog Urol. · Pubmed #18472065 No free full text.

Abstract: A first serum total PSA assay is recommended during the first three months after treatment. When PSA is detectable, PSA assay should be repeated three months later to confirm this elevation and to estimate the PSA doubling time (PSADT). In the absence of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 ng/ml (or less than 0.07 ng/ml) for the ultrasensitive assay method and less than 0.2 ng/ml for the other methods. In the presence of residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A consensus has been reached to define recurrence as PSA greater than 0.2 ng/ml confirmed on two successive assays. After external beam radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 ng/ml (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 ng or more above the PSA nadir, whether or not it is associated with endocrine therapy. After endocrine therapy, the PSA nadir is correlated with recurrence-free survival. PSA is decreased for a mean of 18 to 24 months followed by a rise in PSA, corresponding to hormone-independence. The time to recurrence or the time to reach the nadir and the PSA doubling time after local therapy with surgery or radiotherapy have a diagnostic value in terms of the site of recurrence, local or metastatic and a prognostic value for survival and response to complementary radiotherapy or endocrine therapy. A PSADT less than eight to 12 months is correlated with a high risk of metastatic recurrence and 10-year mortality. The histological and biochemical characteristics in favour of local recurrence are Gleason score less or equal to seven (3+4), elevation of PSA after a period greater than 12 months and PSADT greater than 10 months. In other cases, recurrence is predominantly metastatic. The risk of demonstrating metastasis in the case of biochemical recurrence after total prostatectomy and before endocrine therapy depends on the PSA level and the PSADT. No consensus has been reached concerning the indication for complementary investigations by bone scan and abdominopelvic CT in patients with biochemical recurrence after treatment of localized cancer without endocrine therapy. However, when PSADT greater than six months, the risk of metastasis is less than 3% even for PSA greater than 30 ng/ml. When PSADT less than six months and PSA greater than 10 ng/ml, the risk of metastasis is close to 50%.

Medioni J, Dionysopoulos D, Banu E, Scotté F, Beuzeboc P, Oudard S. · Département de cancérologie médicale, Hôpital européen Georges Pompidou, F-75015 Paris, France. <> · Presse Med. · Pubmed #18160251 No free full text.

Abstract: Chemotherapy treatment for patients with prostate cancer has advanced considerably during the past decade. The first demonstration of the efficacy of palliative chemotherapy in patients with hormone-resistant prostate cancer was followed by FDA approval of mitoxantrone in this setting and by studies showing the usefulness of several different drugs in these patients. Docetaxel became the standard treatment for them. The development of new cytotoxic molecules and targeted therapies as well as the evaluation of the efficacy of docetaxel in earlier stages of prostate cancer, with many ongoing studies, are the current lines of research for improving management of these hormone-refractory patients.

Oudard S, Banu E, Scotte F, Beuzeboc P, Guyader C, Medioni J. · Département de cancérologie médicale, Hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris. · Bull Cancer. · Pubmed #17845995 No free full text.

Abstract: Although the number of men presenting with metastatic prostate cancer has decreased significantly over the last several years, the death rate for those men is essentially unchanged. Effective treatments have not existed for prostate cancer progressing after androgen deprivation therapy until recently. Docetaxel based chemotherapy has demonstrated to extend patient survival in two large randomized studies. These studies have provided the impetus to combine docetaxel with novel biologic drugs to further consolidate the gains in long-term outcome. With the arrival of new therapies such as epothilone analogues, small molecule receptor tyrosine kinase inhibitors, monoclonal antibodies, bone-targeted drugs, antisense oligonucleotides, antiangiogenics drugs and endothelin receptor antagonists, the future of prostate cancer therapy appears promising.

Beuzeboc P, Richaud P. · No affiliation provided · Prog Urol. · Pubmed #15816405 No free full text.

This publication has no abstract.

Fizazi K, Beuzeboc P, Lumbroso J, Haddad V, Massard C, Gross-Goupil M, Di Palma M, Escudier B, Theodore C, Loriot Y, Tournay E, Bouzy J, Laplanche A. · Department of Medicine, Institut Gustave Roussy, Villejuif, France. · J Clin Oncol. · Pubmed #19364971 No free full text.

Abstract: PURPOSE: To assess docetaxel combined with samarium-153-ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m(2)/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA-progression-free survival (PFS) as the primary end point. RESULTS: Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel-samarium-153-EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%). CONCLUSION: Combining docetaxel and samarium-153-EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

Oudard S, Banu E, Beuzeboc P, Voog E, Dourthe LM, Hardy-Bessard AC, Linassier C, Scotté F, Banu A, Coscas Y, Guinet F, Poupon MF, Andrieu JM. · Department of Medical Oncology, Georges Pompidou European Hospital, 20 Rue Leblanc, 75908, Paris Cedex 15, France. · J Clin Oncol. · Pubmed #15738542 No free full text.

Abstract: PURPOSE: Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP). PATIENTS AND METHODS: One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle) and estramustine (280 mg p.o. tid on days 1 through 5 and 8 through 12) or mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg daily). RESULTS: One hundred twenty-seven patients were assessable for PSA response and safety. A > or = 50% PSA decline was found in a greater percentage of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P = .0001). Median time to PSA progression was five times longer with DEP than with MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm (13.4 months), but not significantly so (P = .3). Crossover rates differed significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C, respectively; P = .00001). Treatment-related toxicities were mild and mainly hematologic. CONCLUSION: The results of this randomized phase II study showed significantly higher PSA decline < or = 50% and longer times to progression in HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be proposed in this setting.

Abratt RP, Brune D, Dimopoulos MA, Kliment J, Breza J, Selvaggi FP, Beuzeboc P, Demkow T, Oudard S. · University of Cape Town, South Africa. · Ann Oncol. · Pubmed #15520061 links to  free full text

Abstract: BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.

Pontvert D, Gaboriaud G, Flam T, Jourdan-Da Silva N, Thiounn N, Mammar H, Beuzeboc P, Debré B. · Département d'oncologie radiothérapique, institut Curie, 26, rue d'Ulm, 75248 Paris cedex 5, France. · Cancer Radiother. · Pubmed #18248831 No free full text.

Abstract: PURPOSE: To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity. PATIENTS AND METHOD: Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76Gy, seminal vesicles: 56 to 76Gy, and pelvic lymph nodes: 44Gy to 16.8% of patients. RESULTS: The five-year actuarial overall survival was 94% (95% IC: 90-97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG (P<10(-6) and P<10(-8)). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1-4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, (P=0.02), and for all grades, a correlation with smaller rectal wall volumes (P=0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75Gy (P=0.02, P=0.01, P=0.0007 and P=0.003, respectively). CONCLUSIONS: These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

Soulié M, Beuzeboc P, Cornud F, Eschwege P, Gaschignard N, Grosclaude P, Hennequin C, Maingon P, Molinié V, Mongiat-Artus P, Moreau JL, Paparel P, Péneau M, Peyromaure M, Ravery V, Rébillard X, Richaud P, Salomon L, Staerman F, Villers A. · No affiliation provided · Prog Urol. · Pubmed #18153992 No free full text.

This publication has no abstract.

Oudard S, Banu E, Scotte F, Banu A, Medioni J, Beuzeboc P, Joly F, Ferrero JM, Goldwasser F, Andrieu JM. · Georges Pompidou European Hospital, Medical Oncology Department, Paris, France. · Ann Oncol. · Pubmed #17846024 links to  free full text

Abstract: BACKGROUND: We evaluated the possible use of prostate-specific antigen doubling time (PSA-DT) before chemotherapy initiation as a surrogate marker of survival in hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Data from 250 consecutive metastatic HRPC patients treated with chemotherapy between February 2000 and November 2006 were retrospectively analysed. At least three PSA assays were required within 3 months before chemotherapy. PSA-DT was calculated as ln 2 divided by the slope of the log PSA line, and the difference between two log PSA levels was divided by the time interval. The primary endpoint was overall survival (OS). Survival rates according to PSA-DT were stratified on chemotherapy regimen. Multivariate Cox regression analysis was performed to isolate the impact of PSA-DT on OS, controlling for associate prognostic covariates. RESULTS: Patients received docetaxel- (82%) or mitoxantrone-based chemotherapy. The median PSA-DT was 45 days (range 4.7-1108 days). There were 174 deaths (70%). The median survival was 16.5 months (95% confidence interval [CI] = 12.5-20.5) and 26.4 months (95% CI = 20.3-32.4) for patients with a PSA-DT < 45 and > or =45 days, respectively. In the multivariate setting, the adjusted hazard ratio (HR) was 1.39 (95% CI = 1.03-1.89; P = 0.04), stratified by chemotherapy regimen. CONCLUSION: A short PSA-DT before onset of chemotherapy in HRPC patients was associated with an increased risk of death. This could be useful as a stratification parameter in trials with new drugs in a metastatic setting.

Beuzeboc P, Anonymous00129. · Département d'oncologie médicale de l'Institut Curie, Paris. · Soins. · Pubmed #17419566 No free full text.

This publication has no abstract.

Amsellem-Ouazana D, Cornud F, Conquy S, Beuzeboc P, Massault PP, Vieillefond A, Flam T, Zerbib M, Debré B. · Department of Urology, Hôpital Cochin, Paris, France. · Urology. · Pubmed #16904469 No free full text.

Abstract: We report the case of a 42-year-old man with a synovial sarcoma of the prostate, metastatic at presentation, who after aggressive chemotherapy followed by extensive surgery developed a complex pelvic fistula involving the lower ureter, bladder, and enteral structures. The patient was a poor candidate for surgery because of his short life expectancy and poor health status. Conservative management with bilateral nephrostomy tubes did not allow sufficient fistulous output for symptomatic relief. Using the percutaneous access already in place, we performed bilateral ureteral embolization with coils. Complete ureteral occlusion was obtained with a minimally invasive procedure and allowed total symptomatic relief.

Peyromaure M, Vieillefond A, Boucher E, De Pinieux G, Beuzeboc P, Debré B, Flam TA. · Department of Urology, Cochin Hospital, 27 rue du faubourg Saint-Jacques, Paris, France. · J Urol. · Pubmed #12796679 No free full text.

This publication has no abstract.

McDermott RS, Deneux L, Mosseri V, Védrenne J, Clough K, Fourquet A, Rodriguez J, Cosset JM, Sastre X, Beuzeboc P, Pouillart P, Scholl SM. · Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. · Eur Cytokine Netw. · Pubmed #11956031 No free full text.

Abstract: Tumour expression of the macrophage colony stimulating factor (CSF-1 or MCSF) has been associated with an adverse prognosis in breast cancer, through an effect on the promotion of metastasis. The aim of the present study was to evaluate the clinical relevance of high circulating CSF-1 levels in patients with newly diagnosed breast tumours and correlate CSF-1 with clinico-pathological parameters. A secondary aim was to also measure CSF-1 in patients with other tumour types and at different stages of disease. Using a commercially available ELISA, pre-treatment plasma levels of CSF-1 were assessed, in 471 consecutive patients diagnosed with breast tumours, in 70 patients with newly diagnosed cancer of the head & neck, in 32 men with prostate cancer metastatic to bone and in 39 women with advanced metastatic breast cancer. Mean CSF-1 levels were significantly higher in patients with locally advanced (p <.015) or metastatic breast tumours (p <.048) and in a group of primary breast cancer patients (n = 26) selected for intensive chemotherapy because of multiple adverse tumour characteristics (p <.0002). Mean CSF-1 was also higher in patients younger than 35 years (p <.02) and in post-menopausal patients (p <.03). There was no significant association with tumour histologic type, grade, or other individual histopathologic parameters. No significant association was found between pre-treatment CSF-1 and overall/relapse free survival. Median CSF-1 levels were dramatically higher in patients with newly diagnosed tumours of the head & neck (604 pg/ml), in men with prostate cancer metastatic to bone (627 pg/ml) and women with advanced metastatic breast cancer (867 pg/ml) than those seen in patients with newly diagnosed breast tumours (334 pg/ml). Our data support the hypothesis that CSF-1 may play a functional role in tumour progression to metastasis as has previously been reported in animal models.

Soulie M, Beuzeboc P, Irani J, Davin JL. · No affiliation provided · Prog Urol. · Pubmed #16821362 No free full text.

This publication has no abstract.