Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer.

BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy. Efficacy was measured in terms of non-progression at two months according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's design, 15 non-progressions out of 51 evaluable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg IV until progression, unacceptable toxicities or withdrawal. RESULTS: Among the 54 patients enrolled in the study between November 2009 and July 2014, 45 were assessable for the primary efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2 months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients were treated for more than 30 weeks. Fifty patients experienced at least a related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4 adverse event. Eleven patients had to stop treatment for toxicity. This led to recruitment being halted by an independent data monitoring committee with regard to the risk-benefit balance and the fact that the primary objective was already met. CONCLUSIONS: While the positivity of this trial indicates a potential benefit of temsirolimus for a subset of bladder cancer patients who are refractory to first line platinum-based chemotherapy, the risk of adverse events associated with the use of this mTOR inhibitor would need to be considered when such an option is envisaged in this frail population of patients. It also remains to identify patients who will benefit the most from this targeted therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01827943 (trial registration date: October 29, 2012); Retrospectively registered.

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience.

BACKGROUND: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. METHODS: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. RESULTS: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. CONCLUSION: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study.

OBJECTIVE: To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain. PATIENTS AND METHODS: This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis. RESULTS: The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control 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. CONCLUSION: In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status.

First assessment of whole-brain radiation therapy combined with pemetrexed-based chemotherapy in non-small-cell lung carcinoma: data on safety and efficacy.

The folate antimetabolite pemetrexed was approved for the treatment of patients with metastatic nonsquamous non-small-cell lung carcinoma. Its activity on brain metastases makes pemetrexed attractive in combination with whole-brain radiation therapy (WBRT), but it could also potentially increase toxicity. We examined the medical records of 43 consecutive patients with brain metastases from non-small-cell lung carcinoma. Patients received pemetrexed-based chemotherapy at a dose of 500 mg/m. The median total number of pemetrexed-based chemotherapy cycles was 4 (range: 1-28). During the course of chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n=34) or 20 Gy in five fractions (n=9). The median follow-up time was 30.5 weeks (range: 1-79 weeks). Intracranial progression was a cause of death in nine patients (20.9%). Clinical benefit of WBRT was reported in 30 patients (69.8%). The best radiological response was a complete response in eight patients (18.6%), a partial response in 16 patients (37.2%), stable disease in 11 patients (25.6%), and progression in four patients (9.3%). A stable intracranial disease until the last follow-up was observed in 26 patients (60.5%). The median estimated overall survival was 31 weeks (95% CI: 24-37 weeks). Most WBRT-related toxicities were low and 21 patients (48.9%) had no reported acute neurological toxicity. One patient developed unexplained encephalopathy 5 weeks after WBRT completion in the context of progressive diffuse brain metastases. The combination of pemetrexed with WBRT led to considerable clinical improvement and tumor responses in most patients. Overall neurological toxicity was rather low. A clinical trial is essential for better analysis of the potential synergistic effects of a drug with radiation and evaluation of neurological toxicity.

Primary intracranial extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcomas (EMC) are extremely rare and are usually located in the deep soft tissues of the lower extremities. Less than 10 cases of intracranial EMC have been reported in the literature, making their management and early diagnosis difficult. We present a new case of intracranial EMC occurring in a 70-year-old woman presenting with a right frontal mass initially assumed to be a brain metastasis from breast adenocarcinoma. The optimal management of these tumours is also discussed. Analysis from the literature suggests that complete resection should be recommended, whenever feasible. Although the high risk for relapse after surgery encourages postoperative treatments, relative resistance to both radio-therapy and chemotherapy characterizes EMC. Future perspectives might include multimodal treatments with highly conformal radiotherapy modalities for dose escalation strategies or use of new molecules. Knowledge of these unusual malignant tumours will be the first step for improving patients' outcome.

Knowledge and screening of testicular cancer in the French Armed Forces: a prospective study.

We performed a prospective study in the French Armed Forces regarding testicular cancer. Our primary objective was to assess whether willingness to have a testicular examination by medical doctor could be improved by a self-administered questionnaire through invitation to self-reflection. A total of 415 soldiers were enrolled. The study used a test-posttest design in that soldiers estimated their willingness to have a testicular palpation before and after responding to a self-administered questionnaire. The willingness to have testicular palpation significantly increased after responding to the questionnaire (p < 0.000001). Acceptance of testicular palpation after responding the questionnaire did not change in 82.25%, increased in 15%, and decreased in 2.75%. Analysis of responses to the questionnaire showed that 26.75% of soldiers (n = 107) had previously received general information on testicular cancer and 85.8% (n = 343) declared that they would be delighted if they were proposed a short educational course on testicular cancer. As a conclusion, this study demonstrates that the willingness to have a testicular examination by medical doctor could be easily improved, since there is a strong demand on medical education regarding testicular cancer.

Reapprasial of the role of endocrine therapy in meningioma management.

Recurrent meningiomas constitute an uncommon but significant problem after standard therapy failure. Speculation that meningiomas may be subject to endocrine influence was supported by both immunohistochemical analyses and epidemiological data. Therefore, alternative strategies such as endocrine therapy have been suggested. Although evidence of consistent findings for the role of specific hormonal exposures is mounting, there are numerous discrepancies about the mitogenic effect of hormonal manipulation on meningioma cells. A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic markers but may also facilitate the development of new pathogenesis-based targeted strategies. This review of literature aims to summarize the present state of the art of endocrine therapy in the management of meningiomas, in order to establish whether hormonotherapy could be included in the therapeutic strategy for unresectable and/or progressive tumours in previously irradiated meningioma patients.

Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients?

BACKGROUND: This study was performed to describe the treatment plan modifications after a geriatric oncology clinic. Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center. PATIENTS AND METHODS: Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included. Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed. Oncology data and treatment decisions were recorded before and after this consultation. Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan. RESULTS: Patient characteristics included a median age of 79 years and a predominance of women with breast cancer. About one half of patients had an independent functional status. Nearly 15% presented severe undernourishment. Depression was suspected in 53.1% of cases. One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications. Of the 93 patients with an initial treatment decision, the treatment plan was modified for 38.7% of cases after this assessment. Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan. CONCLUSION: The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases. Further studies are needed to determine whether these modifications improve the outcome of these older patients.

A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis.

BACKGROUND: To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G]), sharper (5-bevel) needle than the 27G/3-bevel needle used previously to inject interferon (IFN) beta-1a, 44 or 22 mcg subcutaneously (sc) three times weekly (tiw), was developed for use in multiple sclerosis (MS). METHODS: Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE) needle shield (a sleeve that houses the tip of the needle in a secure location) is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales); and patient satisfaction (surveys of patients with MS). RESULTS: In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS) and Verbal VAS (VB-VAS); mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p < 0.01). Pooled results from surveys of patients with MS indicated that 63% of patients thought that injections were less painful with the 29G/5-bevel needle than the 27G/3-bevel needle. Results from individual surveys indicated that the 29G/5-bevel needle was an improvement over the 27G/3-bevel needle for ease of insertion, injection-site reactions, bruising, burning and stinging. CONCLUSION: Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw.

Quality of life in cancer patients undergoing anticoagulant treatment with LMWH for venous thromboembolism: the QUAVITEC study on behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

BACKGROUND: Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3-6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. RESULTS: Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81-1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63-2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. METHODS: QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. CONCLUSION: QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

[Testicular metastasis of prostatic adenocarcinoma: a case report]. / Métastase testiculaire d'un adénocarcinome prostatique: à propos d'un cas.

Metastasis of prostate adenocarcinoma to testis is an extremely rare occurrence. Orchiectomy is necessary to confirm histopathological diagnosis. Metastatic carcinoma of the prostate to the testis is a commonly accepted as a sign of disseminated disease. Systemic treatment are therefore required. We report a case of a 62-year-old patient who presented a prostatic carcinoma with a testicular metastasis.

[Accelerated atheroma with prednisone and clopidogrel]. / Athérome accéléré lors d'un traitement par prednisone et clopidogrel.

INTRODUCTION: Several mechanisms may explain the aggravation of atheroma lesions in patients receiving corticosteroid treatments. CASE: This 68-year-old man, a smoker with high cholesterol levels and a history of two transient ischemic attacks, also had severe Horton disease (giant cell arteritis) requiring treatment by corticosteroids and azathioprine. After a new transient ischemic accident, clopidogrel treatment was initiated. Ten months later, severe carotid stenosis was observed. Endarterectomy removed a recent thrombus and the pathology examination showed necrotic lesions complicated by hemorrhage with inflammatory infiltrate. DISCUSSIONS: This patient's atheromatous disease was aggravated by intraplaque hemorrhage, caused by several factors include his corticosteroid therapy and platelet aggregation inhibition treatment.

[Prognosis prediction of febrile neutropenia by MASCC score: A retrospective study]. / Prédiction de la gravité des neutropénies fébriles par le score de MASCC : une étude de cohorte rétrospective.

INTRODUCTION: The score of the MASCC, by means of clinical criteria, estimates the risk of serious complications in patients with neutropenic fever induced by chemotherapy. METHODS: We retrospectively studied a cohort of patients hospitalized for a neutropenic fever and analyzed complications according to the criteria defined by the MASCC. RESULTS: Eighty-one neutropenic fevers in 71 patients were identified. Microbiological documentation was obtained in 33% of cases only. Fifty-eight patients (72%) presented with a MASCC score≥21 and were considered as low risk of complications. In the total population, 10 patients died during their hospitalizations for neutropenic fever, 7 in the high-risk group versus 3 in the low risk group, including 2 patients suffering from significant comorbidities not taken into account by MASCC score. Within the low risk group, presence of a metastatic disease and existence of 2 or more comorbidities were associated with a longer duration of hospitalization. CONCLUSION: This analysis suggests that the criteria of the MASCC are not always enough to thoroughly identify which patients were at risk of complications or could be treated through outpatient management. By better taking into account the comorbidities and tumoral stage, a better selection of the patients who are likely to receive an ambulatory treatment could be made. To date, hospitalization remains frequently necessary in neutropenic fevers, at least in its initial steps, and the place of the general practitioner remains to be better defined.

[Role of general practitioners in cancer screening: A survey in the French armed forces]. / Place du médecin militaire dans le dépistage du cancer : évaluation des pratiques professionnelles.

INTRODUCTION: The French Military Health Service organizes medical survey of 340,000 military men. The aim of the present study was to evaluate the practices of solid cancer screening of general practitioners in military medical units and to compare the results with the recommendations of the French National Institute of Cancer. METHODS: We conducted a prospective, observational study among general practitioners in Army Medical Unit by sending them a self-assessment questionnaire. Physicians should report on their practices for screening cancers with official screening recommendations. Compliance rates with the recommendations were reviewed. Screening practices for other cancers (prostate cancer, melanoma, thyroid cancer, lung cancer, testicular cancer) were assessed. RESULTS: A total of 133 questionnaires were analyzed. Despite a strong involvement of army general health practitioners, guidelines adherence rates (examination frequency, ages of screening beginning and ending) were of 4% for cervical cancer, 7% for breast cancer, and 37% for colorectal cancer. Those rates are comparable to those reported with civilian general practitioners. For cancers without screening recommendation, practitioners felt highly concerned, especially for the most common cancers among the military population. One third of physicians stated that they had diagnosed a testicular cancer through routine screening. CONCLUSION: Military general health practitioners feel themselves concerned by solid cancer screening, and more particularly for cancers that are the most prevalent in young adults. However, current guidelines are neither known nor applied in routine.

[Advanced nonsmall cell lung cancer: importance of chemotherapy in the control of symptoms]. / Cancer bronchique non à petites cellules avancé: intérêt de la chimiothérapie dans le contrôle des symptômes.

Chemotherapy in advanced non-small-cell lung cancer may be a controversy because it is only palliative and costly. Benefit of chemotherapy is nevertheless clear in survival and particularly life quality. Beside this technical criteria, two other factors have an impact on the therapeutic decision: symptom control and patient's personal expectations. The aim of the strategy is to determine an acceptable compromise in each situation.

[Towards an integrated approach to cardiovascular toxicities related to the treatments of breast cancer]. / Vers une approche intégrée des toxicités cardiovasculaires liées aux traitements du cancer du sein.

There is an increasing number of therapeutic options in breast cancer management. While prognosis improves, the cardiac toxicity related to treatments remains a significant issue. This toxicity has several clinical presentations and can be explained by complex and diverse molecular mechanisms. Systemic treatments (anthracyclines, inhibitors of HER2 signaling pathway, hormone therapy, antiangiogenic agents) and radiotherapy have their own cardiac toxicity. However, the toxicities associated with these treatments may potentiate together and the existence of pre-existing cardiovascular risk factors should be taken into account. The assessment of cardiac hazard evolves toward a multifactorial approach. Several possibilities exist to minimize the incidence of cardiac complications. Those include pharmacological and technological innovations, but also a more accurate selection of patients and a growing involvement of practitioners in the field of cardiac toxicity, which is prerequisite for an early management of cardiac events.