[Show abstract][Hide abstract] ABSTRACT: Background: The role of chemotherapy in metastatic non castrate prostate cancer (mNCPC) is debated. Survival benefits of docetaxel (D) added to androgen-deprivation therapy (ADT) were shown in the CHAARTED trial in patients with metastatic high-volume disease (HVD). Objective: To assess the impact of metastatic burden and to update overall survival (OS) data of the GETUG-AFU15 study. Design, setting, and participants: Randomized phase 3 trial of ADT plus D versus ADT alone in 385 mNCPC patients; median follow-up of 7 yr. Outcome measurements and statistical analysis: Primary end point was OS. Secondary end points were biochemical progression-free survival (bPFS) and radiographic progression-free survival (rPFS). Retrospective analysis was by tumor volume. Results and limitations: After a median follow-up of 83.9 mo, median OS in the overall population was 62.1 mo (95% confidence interval [CI], 49.5-73.7) and 48.6 mo (95% CI, 40.9-60.6) for ADT plus D and ADT arms, respectively (hazard ratio [HR]: 0.88 [95% CI, 0.68-1.14]; p = 0.3). Median OS in ADT plus D and ADT arms, respectively, was for HVD patients: 39.8 mo (95% CI, 28.0-53.4) versus 35.1 mo (95% CI, 29.9-43.6) (HR: 0.78 [95% CI, 0.56-1.09]; p = 0.14), for low-volume disease (LVD) patients; median was not reached (NR; 95% CI, 69.5-NR) and 83.4 mo (95% CI, 61.8-NR) (HR: 1.02 [95% CI, 0.67-1.55]; p = 0.9). For upfront metastatic patients, OS was 52.6 mo (95% CI, 43.3-66.8) and 41.5 mo (95% CI, 36.3-54.5), respectively (HR: 0.93 [95% CI, 0.69-1.25]; p = 0.6). The bPFS (HR: 0.73 [95% CI, 0.56-0.94]; p = 0.014) and rPFS (HR: 0.75 [95% CI, 0.58-0.97]; p = 0.030) were significantly longer in the ADT plus D arm. Limitations included the retrospective analysis of metastatic extent and the lack of statistical power to detect a significant difference in subgroups. Conclusions: The post hoc analyses of the GETUG-AFU15 study demonstrated a nonsignificant 20% reduction in the risk of death in the HVD subgroup. Patients with LVD had no survival improvement with early D. Patient summary: In this study, docetaxel added to castration did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues. However, early chemotherapy should be discussed with all patients, given the data of three randomized trials including GETUG-AFU15. After a median follow-up of 7 yr, the randomized phase 3 GETUG-AFU15 study (evaluation of early docetaxel in metastatic noncastrate prostate cancer) showed a nonsignificant 4.7-mo overall survival improvement in patients with high-volume metastatic disease.
[Show abstract][Hide abstract] ABSTRACT: Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. Patients and methods: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). Results: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P= 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. Conclusion: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC.
Full-text · Article · May 2015 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: Background
COU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU.
Between December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors.
Among the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years.
Biochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders’ patients could beneficiate from AA for more than 3 years.
[Show abstract][Hide abstract] ABSTRACT: The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.
Full-text · Article · Oct 2014 · Bulletin du cancer
[Show abstract][Hide abstract] ABSTRACT: The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis.
No preview · Article · Sep 2014 · European Urology
[Show abstract][Hide abstract] ABSTRACT: Background High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage
setting, 30%–70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment,
up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very
poor long-term prognosis, requiring earlier intervention of HDCT.
Full-text · Article · Jun 2014 · Annals of Oncology
[Show abstract][Hide abstract] ABSTRACT: The standard treatment for patients with metastatic GCT relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing 3-drug regimen, which usually yields a complete response (CR) rate <50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study.
The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/d day 1-5, cisplatin 20 mg/m(2)/d, day 1-5, G-CSF 263 µg/d day 7-15, repeated every 3 weeks for 4 cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous complete response (CR) to first-line chemotherapy for metastatic disease. The primary endpoint was the CR rate and a two-stage Simon design was used.
37 patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3-4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression.
In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate.
[Show abstract][Hide abstract] ABSTRACT: Background
The expanded access program and anecdotal cases suggested sunitinib is safe in RCC patients with BM and might have worthwhile activity.
Patients and Methods
In a phase II trial, patients with untreated BM received the standard regimen of sunitinib. The primary end point was objective response (OR) rate in BM after 2 cycles. An OR rate of 35% was prospectively defined as the minimum needed to warrant further investigation. According to Simon's optimal 2-stage design, at least 3 of the initial 15 patients had to have an OR for accrual to continue.
Among 16 evaluable patients, 1 had a complete response outside the central nervous system (CNS). CNS disease was stabilized in 5 (31%). However, no BM showed an OR. Therefore, no further accrual took place. Median time to progression was 2.3 months and overall survival was 6.3 months. There was 1 toxic death, from peritonitis with gastric perforation. Three patients experienced at least 1 treatment-related grade 3 or greater toxicity but no neurological adverse events were attributable to sunitinib.
Although tolerability was acceptable in RCC patients with previously untreated BM, sunitinib has limited efficacy in this setting.
No preview · Article · Feb 2014 · Clinical Genitourinary Cancer
[Show abstract][Hide abstract] ABSTRACT: Brain metastases (BM) can affect up to 45 % of a high-risk breast cancer (BC) population. Liposomal doxorubicin (LD)-based chemotherapy has demonstrated efficacy in the treatment of BC and LD crosses the blood-brain barrier. The aim of this retrospective study is to evaluate the efficacy of the LD-cyclophosphamide (CTX) combination in BM related to BC. Patients diagnosed with BM related to BC and treated with the LD-CTX combination were eligible. BM objective response rate (BM-ORR), BM disease control rate (BM-DCR), BM progression-free survival, overall survival (OS) and safety were analyzed. 29 patients were eligible. The median time from metastatic diagnosis to brain involvement was 12 months. BM was more frequently observed in HER2+ patients. On average, three courses of chemotherapy were administered without grade 3-4 limiting adverse events. After three cycles, BM-ORR and BM-DCR were 41.4 and 58.6 % respectively versus 50 and 62.5 % when no prior radiotherapy was administered. From BM diagnosis, OS was 23 months. A high BM-ORR is observed with the LD-CTX combination in patients with BM related to BC. This is an attractive therapeutic option for these patients, especially when no prior whole brain radiotherapy has been administered.
No preview · Article · Jan 2014 · Journal of Neuro-Oncology
[Show abstract][Hide abstract] ABSTRACT: Toxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer.
The 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed.
Data were available for 220 and 165 patients at 3 and 6months respectively. Physicians systematically under-reported patients' symptoms. Positive agreement rates (at respectively 3 and 6months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians' failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6months.
Physicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients' self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology.
French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen.
Full-text · Article · Jan 2014 · European journal of cancer (Oxford, England: 1990)
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinomas (MCC) are neuroendocrine skin tumours frequently responsible for lymph node recurrence and metastatic disease and for which optimal management remains to be defined. The objective of this study was to evaluate the impact of F-fluorodeoxyglucose (F-FDG)-PET/computed tomography (CT) on the staging and treatment of MCC patients.
Twenty-three patients with a histologic diagnosis of MCC explored by F-FDG-PET/CT between 2004 and 2012 were retrospectively included in the study. The detection of new lesions and the change in tumour staging and treatment were evaluated. For each patient, the F-FDG-PET/CT results were compared with histological, clinical and imaging data.
Sixty-six F-FDG-PET/CT scans were performed at initial presentation (n=18), during subsequent monitoring (n=34) or during evaluation of chemotherapy response (n=14). The sensitivity, specificity and positive and negative predictive values of the F-FDG-PET/CT were 97, 89, 94 and 94%, respectively. Two false-positive results (lymphadenitis) and one false-negative result (regional metastatic lymph nodes) were accounted for. Lesions not detected clinically or by conventional imaging techniques were found in 44% of the 52 F-FDG-PET/CTs performed at initial presentation and subsequent monitoring, with, respectively, 50 and 41% of scans identifying new lesions. At initial presentation, F-FDG-PET/CT led to a change in tumour staging in 39% of patients. Patient management was modified by F-FDG-PET/CT results in one-third of patients (33% of patients at initial presentation, 32% during subsequent monitoring and 36% during evaluation of chemotherapy response). F-FDG-PET/CT incidentally detected four additional histologically confirmed cancers.
This retrospective study confirms the important impact of F-FDG-PET/CT on the management of MCC patients.
No preview · Article · Nov 2013 · Nuclear Medicine Communications
[Show abstract][Hide abstract] ABSTRACT: To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain.
This randomised phase 2 study reports data from 92 patients (52% > 70 yrs-old; 40% PS II) previously treated with taxane-based chemotherapy and collected at 15 centres in France. Patients received intravenous mitoxantrone (MTX), oral vinorelbine (VN), or oral etoposide (EP) associated with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoral responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis.
The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. The control of pain was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose-intensity of treatments, efficacy and safety.
In a population including frailty and/or elderly patients, who are poorly represented in most of the clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen.While new treatment options are now approved, decision-making process should take into account the expected benefit/risk ratio based on the patient status.
No preview · Article · Nov 2013 · BJU International