Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma.

PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma. A French experience.

INTRODUCTION: The value of a nonanthracyclin regimen in thymic carcinoma and malignant thymoma is not well defined. These regimens may be useful in some patients, particularly with cardiac diseases. The objective of this study is to evaluate the response rate, progression free survival, overall survival and toxicity of combined etoposide, ifosfamide, and cisplatin in patients with advanced thymoma and thymic carcinoma. METHODS: From October 1995 to April 2001, 18 patients with advanced thymoma or thymic carcinoma were entered on trial, and receive etoposide (100 mg/m(2) on days 1-3), ifosfamide (1500 mg/m(2) on days 1-3), s and cisplatin (30 mg/m(2) on days 1-3). Cycles were repeated every 3 weeks for a total of six cycles. RESULTS: Among 16 evaluable patients, there were no complete responses and four partial responses (complete and partial responses rate, 25%; confidence interval [CI] 95, 7-48%). The median follow-up was 32.6 months (range, <9-84 months), and the median overall survival has not yet been reached because more than 50% of patients are still alive. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 93.8 and 78.1%, respectively. The toxicity was predominantly myelosuppresion and alopecia. CONCLUSIONS: The combined etoposide, ifosfamide, and cisplatin regimen has moderate activity in patients with advanced thymic tumors. Our results confirm the Eastern Cooperative Oncology Group trial published in 2001. Response rates appear to be lower to many phase II trials, but survival seems similar.

[Environmental cancer: malignant pleural mesothelioma]. / Cancer environnemental: le mésothéliome pleural.

Malignant pleural mesothelioma (MPM) remains an aggressive tumour, but medical interest has recently evolved from almost nihilism to a real interest. Significant advances are observed in the pathologic diagnosis, the staging, the knowledge of the mesothelial carcinogenesis, the identification of biological markers with potential interest in diagnosis or in treatment. Proper management implies the participation of the general population since the implementation of administrative procedures for social and economical compensation. Active and multidisciplinary therapeutic strategies are currently evaluated and the concept of multimodality treatment includes new effective chemotherapies improving survival and quality of life, modern modalities of radiotherapy and pleuropneumonectomy. This advances create hopes and interrogations because it is not currently know whether multimodality treatment will be the standard in MPM.

Phase II study of vinflunine in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM. PATIENTS AND METHODS: Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients. RESULTS: Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively). CONCLUSION: Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.

[Malnutrition in cancer patients]. / Dénutrition chez le patient traité pour cancer.

Malnutrition is common in cancer patients. Many factors contribute to weight loss: some of them can be related to diminished dietary intake, while others are more associated with metabolic changes induced by systemic inflammatory responses. This is why at a specific phase during the course of development, some cancers will benefit from nutritional support, while in theory, and others will benefit from anti-inflammatory treatment. Parenteral nutrition is indicated for severe malnourished surgical patients and for allogenic stem cell transplant patients. Tube feeding (enteral nutrition) should be considered for patients with a functional gut who are unable to ingest sufficient nutrients orally, for example head and neck cancer patients. The value of dietary counselling and oral nutritional support has not been proven in patients undergoing chemotherapy, which is why it is so difficult to propose recommendations. Some arguments seem to favour parenteral nutrition for patients with bowel obstruction suffering from advanced-stage incurable cancer. As the results of studies following omega-3 fatty acid-enriched oral nutritional support in palliative care patients are inconsistent, these products cannot be recommended.

[Asbestos-related occupational cancers]. / Cancers professionnels liés à l'amiante.

Due to its remarkable physical properties asbestos has been widely used in the industry. It is estimated that 25% of present French retired workers have been occupationally exposed to asbestos. A causal relationship between asbestos exposure and respiratory cancers is established since 1955 for lung cancer, and since 1960 for pleural mesothelioma. A causal relationship is also demonstrated for peritoneal and pericardic mesotheliomas, and strongly suspected for laryngeal cancers. It is estimated that occupational exposure to asbestos could be responsible for 5 to 20% of lung cancers and 80 to 90% of pleural mesothelioma, in men, in industrialized countries. The risk of cancer is positively correlated to cumulated exposure. No threshold has been demonstrated below which there is no increased risk of respiratory cancer.

[Management of emesis in cancer patients]. / Prise en charge des nausées et des vomissements chez les patients cancéreux.

Nausea and vomiting are often seen in cancer patients. They can be acute (induced by chemotherapy or radiotherapy...), or chronic in patients with advanced disease. A high percentage of patients (70% to 80%) suffer from chemotherapy induced nausea and vomiting. The incidence and severity of these symptoms depend of the nature of chemotherapy, doses, other drugs used in association, and psychological status of the patients. International guidelines have improved the management of nausea and vomiting, with the use of new drugs like setrons. Despite this, optimal care of refractory and delayed nausea and vomiting after chemotherapy is still a matter of debate. Chronic nausea and vomiting concern more than 50% of patients in palliative situation. The origin is often multifactorial. Management consists in aetiologic and symptomatic treatment in order to improve the patients' quality of life.

Malignant mesothelioma. Medical oncology: standards, new trends, trials--the French experience.

Clinical trials investigating new trends in the treatment of stage I and II malignant mesothelioma have shown both intra-pleural immunotherapy and systemic chemo-immunotherapy to be efficacious. Intra-pleural gamma-interferon (gamma-IFN) therapy was associated with tolerable toxicity and an overall response (ORR) rate of 19%, while treatment with intra-pleural recombinant interleukin-2 (IL-2) was more toxic, but yielded an ORR of 47% in phase I trial and 55% in a phase II study. The association of intravenous cisplatin and subcutaneous alpha-interferon (alpha-IFN) was also associated with an encouraging ORR of 40% and a median survival of 12 months. Treatment with cisplatin, alpha-IFN and mitomycin C was associated with moderate toxicity and an ORR of 21% and a median survival of 12 months. The association of cisplatin, alpha-IFN and IL-2 was, however, extremely toxic and resulted in an ORR of 15%. The majority of patients responding to intra-pleural immunotherapy and systemic chemo-immunotherapy had epithelial type mesothelioma. The most encouraging results obtained from trials investigating systemic chemotherapy were following treatment with cisplatin, 5-fluorouracil, mitomycin C and etoposide, where an ORR of 38% and an overall median survival rate of 16 months were achieved. Toxicity was mainly haematological and tolerable.

Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.

PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

[Management of dyspnea in the cancer patient]. / Prise en charge de la dyspnée chez le patient cancéreux.

Dyspnea is a very common symptom in cancer patients. It is an important symptom because it interferes with patient's quality of life and because its treatment is often difficult. Dyspnea may be defined as an uncomfortable awareness of breathing. Diagnosis relies on physical examination, which intends also to assess severity of dyspnea and etiology. In cancer patients many mechanisms may be involved: tumor progression, side effects of treatments, associated disease especially from cardiac or infectious origin. A specific treatment (whenever it is possible) is associated with symptomatic measures. Oxygen therapy is often used. Morphine can decrease the sensation of dyspnea by its central effects and is useful especially in palliative setting. Benzodiazepines reduce anxiety induced by dyspnea. Physiotherapy, support of patient and family must not be neglected.

[Current insights in malignant pleural mesothelioma]. / Actualités dans le mésothéliome pleural malin.

Faced with the rising incidence of malignant pleural mesothelioma (MPM), the medical community is now busy to improve the care for this pathology. Although there is still no unanimously recognized therapy for MPM, long survival has been observed for some patients treated with associated therapies (surgery + radiotherapy + chemotherapy). However, the detection and the aggressive care of early stages MPM must be justified by a demonstrated survival improvement with conservation of a good quality of life. This article tries to summarize current insights concerning epidemiology, diagnosis and treatment of MPM. At now, more questions than responses exist concerning the care of this severe prognosis disease.