TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes.

BACKGROUND: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. RESULTS: Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. CONCLUSIONS: With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

[French CCAFU guidelines on prostate cancer: hormone-sensitive metastatic prostate cancer-update 2020]. / Recommandations françaises du comité de cancérologie de l'AFU pour le cancer de la prostate : cancer de prostate métastatique hormono-sensible­actualisation 2020.

OBJECTIVE: The aim of the Cancerology Committee of the French Association of urology (CCAFU) is to propose an update of the guidelines in the management of hormone-sensitive metastatic prostate cancer. METHODS: A systematic review (Medline) of the literature from 2018 to 2020 was conducted by the CCAFU Findings. Several patterns can be defined at this stage depending on prognostic, metastatic volume, and whether metastases are synchronous or metachronous. Androgenic deprivation therapy (ADT) remains the mainstay of treatment at the metastatic stage. Docetaxel in combination with ADT improves overall survival in synchronous metastatic prostate cancer. In this situation, the combination of ADT with abiraterone is also a standard of care regardless of tumor volume. Recent data have led to the recommendation that ADT should be used in conjunction with a new generation hormone therapy (Apalutamide or Enzalutamide) in metastatic synchronous or metachronous patients, regardless of tumour volume. Local treatment of prostate cancer with radiotherapy improves survival in synchronous oligometastatic patients. Metastases-directed therapy is being evaluated. CONCLUSION: This update of the French recommendations should help improve the management of patients with prostate cancer.

[French ccAFU guidelines - update 2020-2022: prostate cancer]. / Recommandations françaises du Comité de cancérologie de l'AFU ­ actualisation 2020­2022 : cancer de la prostate.

OBJECTIVE: - The purpose of the guidelines national committee ccAFU was to propose updated french guidelines for prostate cancer. METHODS: - A Medline search was achieved between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of prostate cancer (PCA), and to evaluate the different references specifying their levels of evidence. RESULTS: - The guidelines outline the genetics, epidemiology and diagnosis of prostate cancer, as well as the concepts of screening and early detection. MRI, the gold standard imaging test for localized cancer, is indicated before prostate biopsies are performed. The therapeutic methods are detailed and indicated according to the clinical situation. Active surveillance is a reference therapeutic option for low-risk tumours with a low evolutionary risk. Early salvage radiotherapy is indicated in case of biological recurrence after radical prostatectomy. Androgen deprivation therapy (ADT) remains the backbone therapy in the metastatic stage. Docetaxel in combination with ADT improves overall first-line survival in synchronous metastatic prostate cancer. In this situation, the combination of ADT with abiraterone is also a standard of care regardless of tumor volume. Recent data indicate that ADT should be indicated with a new generation of hormone therapy (Apalutamide or Enzalutamide) in metastatic synchronous or metachronous patients, regardless of tumour volume. Local treatment of prostate cancer with radiotherapy improves survival in synchronous oligometastatic patients. Targeted treatment of metastases is being evaluated. In patients with castration-resistant prostate cancer (CRPC), new therapies that have emerged in recent years help to better control tumor progression and improve survival. CONCLUSION: - These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

[French ccAFU guidelines - Update 2018-2020: Prostate cancer]. / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate.

OBJECTIVE: The purpose of the guidelines national committee ccAFU was to propose updated French guidelines for prostate cancer. METHODS: A Medline search was achieved between 2016 and 2018, as regards diagnosis, options of treatment and follow-up of prostate cancer, and to evaluate the different references specifying their levels of evidence. RESULTS: Epidemiology, classification, staging systems, diagnostic evaluation of prostate cancer are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of≥76Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high-risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a standard. In this situation, the combination of ADT and abiraterone acetate also becomes a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival. CONCLUSION: These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

RETRACTED: Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate French ccAFU guidelines ­ Update 2018­2020: Prostate cancer / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: DOI:10.1016/j.purol.2019.01.007. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the DOI:10.1016/j.purol.2019.01.007. That newer version of the text should be used when citing the article.

Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment.

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.

[CCAFU french national guidelines 2016-2018 on prostate cancer]. / Recommandations en onco-urologie 2016-2018 du CCAFU : Cancer de la prostate.

OBJECTIVES: The purpose of the guidelines national committee CCAFU was to propose updated french guidelines for localized and metastatic prostate cancer (PCa). METHODS: A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of PCa, to evaluate different references with levels of evidence. RESULTS: Epidemiology, classification, staging systems, diagnostic evaluation are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of > 74Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival. CONCLUSIONS: These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer. © 2016 Elsevier Masson SAS. All rights reserved.

[Management of low-risk prostate cancer]. / Prise en charge des tumeurs de la prostate à faible risque évolutif.

INTRODUCTION: The widespread use of prostate cancer screening has led to a stage migration resulting in an increase in the diagnosis of low-risk disease, which currently accounts for 40-50% of diagnosed forms. New therapeutic strategies have been developed in order to minimize the risk of overtreatment. METHODS: A systematic review of the literature over the past 20 years was performed using the Medline database. The literature selection was based on evidence and practical considerations. RESULTS: Low-risk tumors are conventionally defined by the d'Amico classification. The use of multiparametric MRI helps to better characterize these tumors. The contribution of molecular biology remains to be determined in clinical practice. Novel therapeutic options for low-risk disease are currently being evaluated. CONCLUSION: The new therapeutic strategies are evolving. They seek to reduce overtreatment without compromising oncological success.

[Imagery of treated prostate cancer]. / Imagerie post-thérapeutique du cancer de la prostate.

INTRODUCTION: Diagnosis, localization of recurrence in the management of prostate cancer patients with increasing concentrations of tumor serum markers is crucial for treatment planning of the patients. The present review describes the role of prostate MRI and (18) Fcholine PET/computed tomography (CT) in tumor detection and extent, when there is a suspicion of residual or recurrent disease after treatment of prostate cancer. METHOD: A systematic review of the literature was performed by searching in the PUB MED/MEDLINE database searching for articles in French or English published between the last 12years. RESULTS: In patient with a clinical suspicion of recurrence after treatment for prostate cancer, imaging can be used to distinguish between local recurrence and metastatic disease. (11)C-choline PET/CT and pelvic multiparametric MR imaging (mp MRI) are complementary in this indication. In this paper, the current status of imaging techniques used for the staging of patients with suspected locally recurrent or metastatic disease in patients treated for prostate cancer were reviewed. CONCLUSION: Mp MRI of the prostate may be valuable imaging modality for the detection and localization of local recurrence. C-choline PET/CT offers an advantage in detecting metastatic disease to lymph node and bone.

Concurrent administration of trastuzumab with locoregional breast radiotherapy: long-term results of a prospective study.

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55%. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0-126.0). Median age at diagnosis was 52 years (25-83). Internal mammary node (IMN) RT was performed in 227 patients (73.7%). After completion of RT, 26 patients (8.4%) presented an impaired LVEF: 17 (5.5%) of grade 1, 7 (2.3%) of grade 2, and 2 (0.6%) of grade 3. At 48 months, locoregional control rate was 95% [95% CI 92; 98], and overall survival rate was 98% [95% CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

[Prostate cancer surgical margin: review by the CCAFU (Oncology Committee of the French Association of Urology)]. / Les marges chirurgicales dans le cancer de la prostate. CCAFU revue de la littérature.

OBJECTIVE: Literature showed the impact of surgical margin status on prognosis after radical prostatectomy (mostly on biochemical survival). Margin status is an easy self-evaluation of surgical practice to assess. The aim of this paper was to define what a positive surgical margin (PSM) is and how to prevent the occurrence, to precise the impact on survival and how to treat. METHOD: A literature analysis with Pubmed has been performed to 2012, furthermore conclusions of the main congresses with selection committee and review publication have also been studied. RESULTS: PSM is defined as "tumor cells touching the ink on the specimen edge". The most frequent reported incidence is between 15 to 20%. Margin status remains one of the major criteria to determine the need of adjuvant radiotherapy after surgery. Quality of life is not or only lightly modified by radiotherapy with the current techniques. Adjuvant radiotherapy improves biological survival but is synonymous with overtreatment in many times. Salvage radiotherapy has to be quickly performed after Prostate Specific Antigen (PSA) relapse (PSA<1 ng/mL even<0.5 ng/mL). CONCLUSION: This literature review did not allow to suggest superiority of one surgical technique over another. In the same way, the kind of dissection i.e. bladder neck or neurovascular bundle preservation does no clearly modify PSM rate. However, it seems logical to "customize" dissection according to prostate cancer characteristics (D'Amico criteria for instance) guided with multiparametric MRI. Intrafascial dissection has to be applied only to low risk. Lastly, the debate between adjuvant or salvage radiotherapy is always ongoing.

[The non-hormonal treatment of metastatic prostate cancer]. / Le traitement non hormonal de la maladie métastatique du cancer de la prostate.

AIM: To describe drugs used in the non-hormonal treatment of metastatic prostate cancer. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: The metabolic radiotherapy although under-used for this indication, kept a place at the beginning of the disease. Radium-223 chloride seems to have to occupy an important place in the coming years. The chemotherapy, the only recourse until very recently in the castration-resistant prostate cancer, must redefine its place partially. The denosumab provide an interesting alternative to bisphosphonates. CONCLUSION: The non-hormonal treatment of the metastatic disease of the prostate cancer is changing rapidly with the emergence of new molecules. Urologist must know perfectly these new drugs.

[Prostate brachytherapy: indications and outcomes]. / Curiethérapie exclusive du cancer de la prostate par implants permanents : indications et résultats. Revue du CC-AFU.

INTRODUCTION: To summarize the indications and outcomes of low dose-rate prostate brachytherapy with permanent implants. METHODS: Bibliographic database PubMed was searched with prostate cancer and brachytherapy as keywords from 1995 to 2012. RESULTS: The main indication of prostate brachytherapy is the favorable group, but it could be proposed to patients with an intermediate prognostic group if the PSA is ≤ 15 ng/mL or if the Gleason score is 7 (3+4), under cover of a prostate MRI without any extra-capsular extension. Oncologic results are similar to those of surgery or external beam irradiation (EBRT), with a 10-yr biochemical control rate approaching 90%. Urinary toxicity is common during the year following the implant, mainly irritative symptoms; 5 to 15% of patients experienced acute urinary retention. A prostate volume higher than 50 cc or an initial high international prostatic symptom score (IPSS) are predictive of toxicity and are recognized as relative contraindications of the technique. Sexual activity is maintained in 60% of patients. CONCLUSION: Brachytherapy must be proposed as a validated option beside active surveillance, surgery and EBRT.

[CCAFU Recommendations 2013: Prostate cancer]. / Recommandations en onco-urologie 2013 du CCAFU : Cancer de la prostate.

INTRODUCTION: The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. METHODS: Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. RESULTS: Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. CONCLUSION: From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined.

[Chemotherapy in perioperative setting for infiltrative bladder cancer]. / Chimiothérapie périopératoire des carcinomes urothéliaux infiltrants de vessie de stade localisé. Une revue de la littérature du groupe vessie du CC-AFU.

INTRODUCTION: Despite an aggressive initial treatment, only 60% of patients with T2-staged bladder tumours, 50% with T3a and 15% with T3b staged-tumours will be alive at 5 years. The purpose of this review is to clarify the potential role of chemotherapy in localised urothelial tumours, which has not been clearly defined. MATERIALS AND METHODS: To address this question, we reviewed published randomized trials of chemotherapy in urothelial tumours of the bladder in both neoadjuvant and adjuvant settings from 1980 and 2010 and corresponding meta-analyses in PubMed. RESULTS: In the neoadjuvant setting, a meta-analysis of individual data from 3005 patients demonstrated an absolute survival benefit of 5.5% at 5 years. Despite these results, neoadjuvant chemotherapy is very rarely proposed in this indication. Comparative trials performed in the adjuvant setting have been limited by major methodological weaknesses, preventing definitive conclusions. In a meta-analysis based on individual data from 491 patients, a 25% reduction in death risk was observed for an absolute gain of 9% at 3 years. CONCLUSION: In light of these data, chemotherapy should be offered early and proposed as a reasonable option for patients for tumours with extravesical extension or with nodal involvement detected postoperatively, neoadjuvant chemotherapy is the standard of care.

[Lymphadenectomy and prostate cancer: a statement of the committee of cancerology of the French Association of Urology]. / Le curage ganglionnaire dans le cancer de la prostate: une mise au point du comité de cancérologie de l'association française d'urologie.

Lymph node invasion is the first step of metastatic evolution of prostate cancer. In this case, today, no local treatment should be proposed. Detection of lymph node invasion is performed by CT-scan and RMI, which show hypertrophied nodes. No difference in term of sensibility and specificity is observed between CT-scan and RMI. Invaded nodes are defined by modifications of size, form, and aspect of the architecture of nodes. Sentinel node belongs to expert centers. Surgical lymphadenectomy remains the best way to evaluate lymph node status. Limited to ilio-obturator land, it underestimates the risk of lymph node invasion: Extended lymph node excision defined by the association of bilateral ilio-obturator, internal iliaca and external iliaca lymphadenectomy should be systematically proposed to intermediate and high risk prostate cancer. A "well done" lymphadenectomy is represented by more than 10 nodes removed. Lymph node invasion represents bad prognosis. However, therapeutic value and influence of prognosis of lymphadenectomy in prostate cancer is still not established. Therefore, one or two invade lymph nodes represented a population of patients with better prognosis, specially if no capsular effraction is observed. After radical prostatectomy, in case of lymph node invasion, immediate hormonotherapy is the standard; however, this treatment is discussed in case of low number of invaded nodes (one or two) and if postoperative PSA is equal to zero. In this case, radiotherapy is still in evaluation and chemotherapy has no indication.

[5 alpha-reductase inhibitors and prostate cancer: a statement of the Committee of Cancerology of the French Association of Urology]. / Inhibiteurs des 5 alpha-réductases et cancer de la prostate : une mise au point du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Two randomised trials and negative conclusion of the FDA about inhibitors of 5 alpha-reductase in prevention of prostate cancer need a revision of the indications of these drugs. METHODS: After description of fundamentals data, review of the literature in PubMed library was performed to analyse the indications of these drugs according to the different stages of prostate cancer. RESULTS: Even if PCPT and REDUCE studies showed a decrease of cancers with the use of 5 alpha-reductase (5ARI) but with side effects, there is no indication for prostate cancer prevention by these drugs. In the same way, despite the results of REEDEM study, there is no indication of these drugs in active surveillance. CONCLUSION: Despite the large interest of these drugs, no recommendation can be given for indications of 5ARI in prevention or treatment of prostate cancer.

Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial.

BACKGROUND: In the evolution of metastatic castration-resistant prostate cancer (mCRPC), patients present visceral metastases with or without neuroendocrine differentiation in 20% of cases. PATIENTS AND METHODS: We assessed the efficacy and toxicity of a platinum-based chemotherapy regimen in mCRPC patients with either neuroendocrine differentiation defined by high serum levels of chromogranin A (CgA) and neuron-specific enolase (NSE) or visceral metastases. Patients received the combination of carboplatin and etoposide every 3 weeks. Efficacy end points included prostate-specific antigen (PSA) and neuroendocrine marker response, objective response and toxicity. RESULTS: Of the 60 patients included from April 2005 to January 2008, 78.6% had bone metastases, 46.4% had lymph node involvement and 57.1% had liver and/or lung localizations. The objective response rate was 8.9% in the 46 patients with measurable disease. A neuroendocrine response was observed in 31% of cases for NSE and 7% for CgA. The PSA response rate was 8%. The most common grade 3-4 treatment-related toxic effects were neutropenia (65.5%), thrombocytopenia (32.7%) and anemia (27.3%). There was 7.2% febrile neutropenia, with one toxicity-related death. The median follow-up was 9.3 months [95% confidence interval (CI) 0.2-27.1] and the median overall survival 9.6 months (95% CI 8.7-12.7). CONCLUSION: The benefit-risk ratio of this regimen seems unfavorable due to poor response and high toxicity.