Real-World Outcomes of Combination Chemotherapy with Trabectedin plus Pegylated Liposomal Doxorubicin in Patients with Recurrent Ovarian Cancer: A Single-Center Experience.

BACKGROUND: Trabectedin plus pegylated liposomal doxorubicin (PLD) proved efficacious as second-line treatment for patients with recurrent ovarian cancer (ROC). METHODS: We report a single-center retrospective analysis of the efficacy and tolerance of trabectedin 1.1 mg/m2 every 3 weeks in a cohort of real-life ROC patients. RESULTS: From February 2012 to January 2014, 17 patients were treated with trabectedin alone or combined with PLD. Median age was 61 years (range: 48-78). Performance status was 0-1 in 16 patients (94%). Disease response rate was 53% and disease control rate was 76%. At the end of the follow-up, 8 patients (47%) were alive. Median overall survival was 17.6 months (95% CI 13.6 to not reached). Median progression-free survival was 6.7 months (95% CI 5.4-10.0). The most frequent grade 3-4 toxicities were neutropenia (n = 4, 24%) and nausea/vomiting (n = 4, 24%). CONCLUSION: Trabectedin combined with PLD seems efficient in and well tolerated by real-life ROC patients.

Translating Clinical Evidence-Based Medicine into the Real World: Single-Center Experience with Cabazitaxel in Metastatic Prostate Cancer Patients.

BACKGROUND: We studied the efficacy and safety of cabazitaxel in unselected real-life patients. PATIENTS AND METHODS: We retrospectively investigated all patients with metastatic prostate cancer (mPC) treated with cabazitaxel 25 mg/m2 i.v. every 3 weeks combined with oral prednisolone (10 mg once daily) after first-line docetaxel chemotherapy. Study issues were to report patient characteristics and cabazitaxel data in terms of tolerance and efficacy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. All data were compared with TROPIC results. RESULTS: From 2011 to 2014, 41 patients received cabazitaxel; 15 patients (37%) had a performance status (PS) ≥2 versus 7% (p < 0.0001) in TROPIC, and 38 patients (93%) presented a Gleason score ≥7 at baseline (vs. 60%; p < 0.0001). All patients had metastatic disease at baseline. Previous therapies were radiotherapy in 17 patients (41 vs. 61%; p = 0.01) and surgery in 24 patients (59 vs. 52%; p = 0.4). The median number of cabazitaxel cycles was 5 (1-10) versus 6 (3-10) in TROPIC. Five patients completed 10 cycles of cabazitaxel (12%) versus 28% in TROPIC (p = 0.03). Toxicities were anemia (12 patients, 29%), diarrhea (9 patients, 22%), nausea (7 patients, 17%), pain (6 patients, 15%), sepsis (4 patients, 10%), neutropenia (3 patients, 7%) and urinary tract infection (1 patient, 2%). The tumor response rate was 19.5 versus 14.4% in TROPIC (nonsignificant). PFS was 4.5 months (95% CI 3.3-6.4) in our analysis and 2.8 months (95% CI 2.4-3.0) in TROPIC. OS was 12.1 months (95% CI 9.2 to not reached) and 15.1 months (95% CI 14.1-16.3), respectively. CONCLUSION: In our unselected mPC patients with poorer baseline clinical conditions and aggressive disease, cabazitaxel seems efficient and not more toxic than in the TROPIC study.

The Combination of 80 Years of Age and Metastatic Castration-Resistant Prostate Cancer Remain an Uphill Battle: A Case Report with Cabazitaxel as a Double-Edged Sword.

We report the case of an 80-year-old patient who presented with a progressive prostate metastatic cancer with poor performance status. The patient had already benefitted from docetaxel and abiraterone. A new line of chemotherapy by cabazitaxel was started with good response, and there was a dramatic improvement in general status and pain symptoms. Age and performance status alone should not be limiting decision factors for elderly cancer patients.

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.

Prolonged temozolomide for treatment of glioblastoma: preliminary clinical results and prognostic value of p53 overexpression.

We report retrospective data on the feasibility and efficacy of prolonging adjuvant temozolomide (TMZ) more than 6 months after chemoradiotherapy completion in patients with glioblastoma (GBM). Molecular prognostic factors were assessed. Data from 46 patients were reviewed. Patients received postoperative irradiation, 60 Gy in 30 fractions, combined with concurrent TMZ, 75 mg/m(2). Four weeks later, adjuvant TMZ was prescribed, 150-200 mg/m(2) for a total of 24 cycles unless there was progression or toxicity. Tumor samples were tested for the following prognostic factors: EGFR overexpression, 1p19q deletion, p53 overexpression and proliferation index. Overall survival (OS) was 84.8% at 6 months, 54.3% at 12 months, 26.1% at 18 months, and 21.7% at 24 months. Progression-free survival (PFS) was 73.9% at 6 months, 34.8% at 12 months, 15.2% at 18 months and 10.4% at 24 months. In the adjuvant phase, no treatment disruption for toxicity was necessary but eight patients required dose adaptation because of side effects. No significant molecular prognostic factor was evidenced for OS. We found that p53 overexpression was the only significant prognostic factor for PFS, with a median PFS of 9.3 months versus 7 months for patients without p53 overexpression (P = 0.031). This study suggests that delivering adjuvant TMZ therapy for more than 6 months is feasible in patients with GBM. Efficacy data warrant further prospective assessment with the focus on molecular prognostic factors, such as p53 overexpression, which was found to be the only significant molecular prognostic factor for outcome.

[Towards a better use of midazolam in end of life: A survey in a department of medical oncology]. / Appel à une meilleure utilisation du midazolam en fin de vie : évaluation des pratiques professionnelles dans un service d'oncologie médicale.

INTRODUCTION: At the end of life of cancer patients, sedation is sometimes needed, in order to palliate unbearable symptoms that other treatments fail to relieve. Midazolam is currently recommended for sedation and its prescription is guided by national guidelines. The aim of the present study was to evaluate the practices of midazolam prescription in a department of medical oncology and to compare the results with French national recommendations in order to improve the midazolam use in case of sedation. METHODS: We conducted a retrospective survey studying midazolam prescriptions in patients who died between 2014 and 2015 in the medical oncology department. Compliance rates with recommendations were reviewed. RESULTS: A total of 99 medical files were analyzed. Fifty-three patients received midazolam: 64.4% for refractory symptoms, 22% for anxiolyse, 10.2% for acute respiratory distress syndrome. When reported, the titration indications and modalities systematically conformed to guidelines. In case of sedation for refractory symptoms, adherence to guidelines was 76% regarding the family information, 63% regarding the patient information, 61% regarding the collegial nature of the initiation decision, 34% regarding the titration achievement and 5% regarding the pluridisciplinary nature of the initiation decision. CONCLUSION: Although limited justifications in midazolam prescriptions could have resulted in an overestimate of sedation and in an underestimate of titrations, current guideline are not enough applied in routine, especially regarding the necessity of a pluridisciplinary decision-making. A list of requirements before midazolam initiation is suggested, to increase the adherence to guidelines. Our results highlight the necessity of a better midazolam use in life-end sedations.

[Validation of a questionnaire assessing patients' adherence and skill level of management for oral capecitabine treatment]. / Validation d'un questionnaire mesurant l'adhérence et les compétences de gestion des effets secondaires chez des patients traités par capécitabine.

INTRODUCTION: There is a plea for the development of tools allowing the screening of fragile patients under oral chemotherapy. Such tools would identify patients with difficulties for being adherent or for having low side effects management skills. The aim of this study is to validate psychometric characteristics of a questionnaire assessing patients' adherence and skill level of management for oral capecitabine treatment. METHODS: Questionnaire's psychometric validation study. Prospective monocentric cohort. Cases-simulated questionnaire was constructed, according to recommendations, from the results of a socio-anthropological study. Validation phases included: a pre-testing and a field-testing including acceptability, scale reliability and internal consistency were conducted involving experts and patients sample. RESULTS: Pre-testing excluded 1 item. Acceptability phase included 15 patients, who did not change any of the questions. Reliability and internal consistency were tested with 67 patients. Cancer site did not statistically influence questionnaire answers. No correlation was identify with the analyse performed for the internal consistency testing. CONCLUSION: This questionnaire has shown to be a valid tool for the assessment of the adherence and side effect management skill for patients with capecitabine treatment. It can easily be uses as a screening tool for prescribers. It can also be used as an evaluation tool for a therapeutic education programme in this field.

Uterine and ovary carcinosarcomas: outcome, prognosis factors, and adjuvant therapy.

OBJECTIVES: The aim of this study was to assess the outcome and the prognosis factors of uterine and ovarian carcinosarcomas. METHODS: From January 1993 to January 2010, data from 68 consecutively treated patients with uterine (n=59) and ovarian (n=9) carcinosarcomas were retrospectively analyzed in a single French comprehensive cancer center. RESULTS: The median follow-up was 24.2 months (interquartile range [IQR]: 13.5 to 54.6). The median age was 69 years (IQR: 63 to 77). Patients were classified as FIGO stage I (n=28; 41%) and FIGO stage II to IV (n=40; 59%), respectively. There were 33 (49%) and 29 (43%) homologous and heterologous type, respectively. The median disease-free survival and overall survival were 21.9 months (IQR: 7.9 to 22.3) and 27.1 months (IQR: 14.5 to 72), respectively. No statistical differences of survival were reported concerning the initial location of the carcinosarcoma (uterine vs. ovarian). Radiation therapy (hazards ratio [HR]=0.3; 95% confidence interval [CI], 0.16-0.67) and FIGO stage I (HR=0.4; 95% CI, 0.17-0.9) were associated with an increased disease-free survival. Homologous type (HR=3; 95% CI, 1.4-6.3) and FIGO stage II to IV (HR=2.64; 95% CI, 1.3-5.4) were associated with a decreased overall survival. There was no survival improvement for the 12% of patients receiving a multimodal adjuvant therapy. CONCLUSIONS: Uterine and ovary carcinosarcomas present a worse prognosis. On the basis of the present study data, although it should be prospectively confirmed, a sequential or multimodal adjuvant therapy should be proposed to patients with early-stage uterine and ovary carcinosarcomas.

Real-World Vinflunine Outcomes in Bladder Cancer in a Single-Institution Study: Moving Beyond Clinical Trials.

PURPOSE: Intravenous vinflunine 320 mg/m(2) every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU. PATIENTS AND METHODS: We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine. RESULTS: Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%). CONCLUSION: Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment.

Hypofractionated radiation therapy for treatment of bladder carcinoma in patients aged 90 years and more: A new paradigm to be explored?

INTRODUCTION: There are only scarce data on the optimal management of patients who present with a bladder carcinoma and who are aged 90 years and older. PATIENTS AND METHODS: We retrospectively reviewed records from radiotherapy departments from two university hospitals, two private centers and one public center to identify patients who underwent radiotherapy for bladder cancer over the past decade and who were aged 90 years or older. From 2003 to 2013, 14 patients aged 90 years or older receiving RT for bladder malignant tumors were identified. RESULTS: Mean age was 92.7 years. Ten patients (71 %) had a general health status altered (PS 2-3) at the beginning of RT. A total of 14 RT courses were delivered, including six treatments (43 %) with curative intent and eight treatments (57 %) with palliative intent. Palliative intent mainly encompassed hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete response, one patient (7 %) experienced partial response, three patients (21 %) had their disease stable, and three patients (21 %) experienced tumor progression, of whom two patients with the progression of symptoms. There was no reported high-grade acute local toxicity in 14 patients (100 %). One patient experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms. At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of death for five patients. CONCLUSION: Hypofractionated radiotherapy remains feasible for nonagenarians with bladder cancer. Further investigations including analysis of geriatric comorbidities and impact of treatments on quality of life should be conducted.

Correlation between anthropometric parameters and acute skin toxicity in breast cancer radiotherapy patients: a pilot assessment study.

OBJECTIVE: The objective of the present study was to identify acute skin toxicity risk factors linked to the anthropometric characteristics of patients with breast cancer treated with radiation therapy. METHODS: Consecutive patients with breast cancer were enrolled after breast-conserving surgery and before radiotherapy course. Acute skin toxicity was assessed weekly during the 7 weeks of radiotherapy with the International Classification from National Cancer Institute. Grade 2 defined acute skin toxicity. Patient characteristics and anthropometric measurements were collected. RESULTS: 54 patients were enrolled in 2013. Eight patients (14.8%) had grade ≥2 toxicity. The average weight and chest size were 65.5 kg and 93.6 cm, respectively. Bra cup size is significantly associated with a risk of grade 2 dermatitis [odds ratio (OR) 3.46, 95% confidence interval (CI) (1.29-11.92), p = 0.02]. Anthropometric breast fat mass measurements, such as thickness of left [OR 2.72, 95% CI (1.08-8.26), p = 0.04] and right [OR 2.45, 95% CI (0.99-7.27), p = 0.05] axillary fat, are correlated with an increased risk. Distance between the pectoral muscle and nipple is a reproducible measurement of breast size and is associated with acute skin toxicity with significant tendency (OR = 2.21, 95% CI (0.97-5.98), p = 0.07). CONCLUSION: Breast size and its different anthropometric measurements (thickness of left and right axillary fat, nipple-to-pectoral muscle distance) are correlated with the risk of skin toxicity. ADVANCES IN KNOWLEDGE: The present article analyses several characteristics and anthropomorphic measurements of breast in order to assess breast size. A standardized and reproducible protocol to measure breast volume is described.

[Assessment of screening in women cancers and in 75 years older in Loire department]. / Évaluation du dépistage des cancers de la femme et du dépistage après 75 ans dans le département de la Loire.

In France, there is an important interregional disparity concerning participation to cancer screening programs. The aim of this study was to assess oncologic screening practices in Loire, a French rural department, in women and in the elderly (over age 74 years). For this, two surveys were conducted. The first one was regarding screening for breast, cervical and colorectal cancer in women over age 18 years living in Loire. The second survey was regarding onco-geriatric screening through two questionnaires : one for the elderly and the other for general practitioner (GP) of the department, evaluating screening for breast, colorectal, prostate, cervical and lung cancer. One hundred sixty six women were included in the first investigation mean age of 47.6 years. Ninety three point six per cent were screening for breast cancer, 19% received Human Papilloma virus vaccine, 83.1% were screening by Papanicolau smear for cervical cancer and finally, 51.7% were screening for colorectal cancer, among the one entering screening program criteria. In the second survey, 44 patients and 28 GP were included. Thirty-eight point six per cent of patients over 74 years continue screening. Only 11.4% were reluctant to screening and in 80% because of anxiety du to the results. Among GP, 50 % continued screening on two major criteria : life expectancy and performans status. The present study shows heterogeneity of screening in this department both rural and working class and gives us a societo-medical photography.

[Re-entrainment to physical activity in the global management of breast cancer: pilot study in a mono-institutional experience]. / Réentraînement à l'activité physique dans la prise en charge globale du cancer du sein: étude pilote monocentrique.

The objective of the present study is to report the pilot experience at the "Loire cardiorespiratory readaptation center" of re-entrainment of physical activity for patients suffering from breast cancer. Between January 2012 and February 2013, 63 patients took the program at the readaptation center. The program is composed of three sessions a week during seven weeks. During the care, a medical team intervenes. It is composed of a cardiologist, a physiotherapist, a sophrologist, a psychologist and a dietician who take part in turns and/or together. During the first session of the program, the warm-up power chosen on the exercise bike was on average of 14.72 watts (min = 5; max = 30), and it went up to 44.84 watts (min = 15; max = 85) on average during the last session. The maximal power used by the patient was on average of 39.08 watts (min = 10; max = 70) during the first session. On the last day of training, the average maximal power between the patients was of 76.03 watts (min = 30; max = 110). The tests used into practice tend to confirm a physical progression between the beginning and the end of the re-training program. This study particularly shows that it is possible today to propose this type of program to the patients in daily practice.

[Carcinosarcomas in female genital tracts: general review]. / Carcinosarcomes gynécologiques: revue générale et principes de prise en charge.

Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.

Feasibility of radiation therapy in patients 90years of age and older: a French multicentre analysis.

BACKGROUND: There are only scarce data on the management of patients aged 90years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90years or older receiving RT. METHODS AND MATERIALS: Records from RT departments from five institutions were reviewed to identify pts 90years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours' characteristics were examined, as well as treatment specificities and treatment intent. RESULTS: 308 pts receiving 318 RT courses were identified, mean age was 93.2years (standard deviation 2.8). Treatment was given with curative and palliative intent in 44% and 56%, respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery and tumour stage. Median total prescribed dose was 36Gy (4-76Gy). Hypofractionation and split course were used in 88% and 7.3%, respectively. Most toxicities were mild to moderate. RT could not be completed in 23 pts (7.5%). No long-term toxicity was reported. Median overall survival was 22.9months (95CI: 15.5-42.7months). Cancer was the cause of death in 8.7% and 46% of pts treated with curative and palliative intent, respectively. CONCLUSION: This study shows that RT is feasible for patients aged 90years or more. PS, place of life and tumour stage were factors of the therapeutic decision. There is no reason to withdraw pts with good general health condition from potentially curative RT, provided that careful attention is paid to factors of toxicity and to geriatric vulnerabilities.

General management of nonagenarian patients: a review of the literature.

The number of nonagenarian people in the world is steadily growing. This phenomenon will increase in future years: in 2050, world population prospects estimate 71.16 million people aged 90 years or older. The two main causes of death among people aged 85 years or more in Europe in 2003 were cardiovascular and cerebrovascular diseases and cancers. However, the elderly are often excluded from clinical trials; they are underrepresented in clinical registries and especially nonagenarians. Care (medical, surgical, oncology) of these very elderly is currently insufficiently based on scientific recommendations. For the physician, the choice to treat or not to treat very elderly patients (for fear of side effects) is difficult. Oncology is particularly affected by this problem. Here we review these different fields of internal medicine management of nonagenarian patients with a special focus on oncology and on comprehensive geriatric assessment as a base for all care decision taking.

A mucoepidermoid carcinoma in a young man with intellectual disability: review of oral cancer in people with intellectual disability.

Oral tumors in patients with intellectual disabilities (ID) remain poorly documented, despite cancer incidence suggesting that malignancies are globally as frequent in this group as in the general population. A clinical case of a 36-year-old man with severe ID presenting with a mucoepidermoid carcinoma of intermediate grade in the right mandible is reported. Delayed diagnosis and problems managing complementary chemotherapy and radiotherapy are described. The literature review reported only 27 cases of malignant tumors in patients with ID. This finding indicates that oral tumors in patients with ID may be less frequent than in the general population, are usually diagnosed at an advanced stage, and may occur in patients who are younger than the general population. Diagnosis and treatment are difficult, implying a comprehensive knowledge of the underlying condition of each individual and the need for good communication skills to obtain patient cooperation, including an understanding of how the patient expresses pain.

[Management of vaginal carcinoma in patients over 70 years old: advantage of a radiotherapy-brachytherapy association]. / Prise en charge du cancer primitif du vagin chez la femme de plus de 70ans: intérêt d'une association radiothérapie-curiethérapie.

OBJECTIVE: Report and discuss the management of the primitive vaginal cancer in elderly adults at a single institute. PATIENTS AND METHODS: Data from patients more than 70 year-old treated for a primitive vaginal cancer at the Institut de Cancérologie de la Loire Lucien-Neuwirth was retrospectively collected. RESULTS: From August 1999 to January 2009, 9/24 patients treated for a primitive vaginal cancer had more than 70 year-old. The median age was 81 years (7-94 years). Most patients had a performance status less or equal to 1 (n=6), a squamous cell carcinoma (n=7) and a FIGO stage less or equal to II (n=6). All patients were treated with 3D external beam radiation, 3 received concurrent chemotherapy, 3 had a supplementary brachytherapy, and 6 had a colpohysterectomy. Among 7 evaluable patients, there were 4 complete responses, 2 partial responses and one progression. Main acute toxicities were gastrointestinal (n=5), urinary (n=3), general (n=3) and cutaneous (n=2). Three patients experienced late toxicities. Four patients had a local recurrence after a mean delay of 10.8 months. At last news, 4 patients were still alive and 4/5 deaths were related to the cancer. All (n=3) patients who received the combination of radiotherapy - brachytherapy were alive and disease-free. Median overall survival was 18 months. DISCUSSION AND CONCLUSIONS: Primitive vaginal cancers are rare and aggressive tumours. Our results suggested the feasibility of the combination of radiotherapy and brachytherapy for elderly patients. Prospective trials remain needed to better define and validate the optimal strategy, especially in elderly adults.

Reappraisal of the role of bevacizumab in the therapeutic strategy in advanced renal cell carcinoma.

Increased understanding of the molecular pathophysiology of metastatic renal cell carcinoma (mRCC) has led to development of antiangiogenic therapies in the past 5 years that significantly improved the prognosis. Vascular endothelial growth factor (VEGF) is a major growth factor in tumor angiogenesis and is implicated in tumor progression of several types of cancer, including mRCC. Use of 2 distinct approaches resulted in clinical efficacy in blocking the VEGF pathway: small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, axitinib, pazopanib) and the humanized anti-VEGF monoclonal antibody bevacizumab that binds circulating VEGF and prevents activation of the VEGF receptor. In the 2 large phase III trials AVOREN and CALGB 90206, bevacizumab combined with interferon alfa demonstrated its efficacy as a first-line therapy in terms of progression-free survival. Nevertheless, in the era of targeted therapies, other studies are still needed to better obtain the maximal clinical benefit of bevacizumab. The aim of this overview is to report the current role of bevacizumab in the treatment of metastatic kidney cancer and to highlight possible combinations or sequential strategies that involve other targeted agents.

[Cisplatin or carboplatin, that is the question]. / Cisplatine ou carboplatine, telle est la question.

Platine-based chemotherapy agents are major drugs in oncology and are currently used in most solid malignancies. Of these, cisplatin has been the most widely used over past years. Its efficacy and toxicity have been both well documented in the literature. Carboplatin has a rather different toxicity profile and seems to be better tolerated than cisplatin. This might potentially impact on quality of life. Carboplatin has been assessed for treatment of most malignancies in which cisplatin has demonstrated its efficacy. This paper aims at reviewing and comparing the current indications in terms of efficacy and toxicity of cisplatin and carboplatin. Although cisplatin has demonstrated its superiority over carboplatin for treatment of lung cancers and germ-cell tumors, the tolerance of carboplatin is better than that of cisplatin. This might be taken into account for patients treated with non-curative attempt. Further studies should compare both chemotherapy agents for quality of life. Of course, carboplatin remains widely used for patients who are contra-indicated for cisplatin.