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Biomedical subjects

P Ruffié

Publications and source records attributed to P Ruffié.

At least 19 recordsLinked to original sources
PubMed2005

[Thymic tumors].

Thymomas and thymic carcinomas are rare and slow-growing tumors, which develop within the anterior mediastinum. Thymomas are often associated with autoimmune disorders and most particularly myasthenia gravis. The treatment of choice remains a complete surgical resection. Postoperative radiotherapy is often combined in case of invasive thymoma invading into adjacent organs. Postoperative radiotherapy in stage II with invasion into capsule has been more controversial lately. In inoperable locally advanced, or metastatic thymic tumors, neoadjuvant cisplatin-based followed by surgery and radiotherapy has given interesting results in the past years.

Carcinoma↗
PubMed2005

[Spinal cord compression from a malignant pleural mesothelioma].

Thoracoscopy-talc led to the diagnosis of epithelial pleural mesothelioma in a 58-year-old man who presented with pleurisy. The course was rapidly unfavorable despite systemic chemotherapy. Dorsal pain revealed invasion of the spine and spinal canal leading to cord compression three months after the diagnosis of mesothelioma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

[Modalities of radiotherapy in small cell lung cancer: thoracic radiotherapy and prophylactic cerebral irradiation].

Small cell lung cancers (SCC) represent 20% of all lung cancers. After the initial control of the extension, only one third of the patients with SCC will finally have limited disease. The treatment of limited SCC currently relies on chemo-radiotherapeutic combinations that have improved overall survival and survival without metastases over the last few years. Nevertheless, even in limited forms, survival at 5 years varies from 10 to 15% and rarely exceeds 25% in the best series. The risk of relapse is high: although around 70% of patients with a limited form will have complete response, only 15 to 20% of them will exhibit prolonged survival. Indeed, most patients relapse, and the risk of cerebral dissemination for example is particularly high, reaching 50% at 2 years even in complete responders. After the results of a meta-analysis evaluating prophylactic cranial irradiation (PCI) among SCC complete responders, demonstrating 5% enhancement of survival at 3 years, PCI is part of the standard management of SCC in complete response. Despite the improvement in overall survival with the combined treatments, the mediocre results observed in terms of long-term survival warrant further clinical trials in order to define the optimal polychemotherapeutic and radiotherapeutic modalities, the best means of combining these two therapies and the place for new therapies.

Brain Neoplasms↗
PubMed2003

Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study.

PURPOSE: The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks. RESULTS: Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported. CONCLUSION: The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.

Adult↗
PubMed2002

[Malignant pleural mesothelioma. From diagnosis to prognosis].

EPIDEMIOLOGY: The incidence of malignant pleural mesothelioma has constantly increased over the past forty years. The recent measures of ban on the use of asbestos and the long latency of this tumor after exposure means that its peak incidence can be foreseen for the years 2010-2020. DIAGNOSIS: Various health professionals are involved in the care of this tumor, which benefits equally from progresses in clinical and fundamental research. Some progress has been made in understanding its oncogenesis as well as its histopathologic analysis. PROGNOSIS: Malignant pleural mesothelioma symptoms are rapidly invalidating and the patient's prognosis is bad at short-term. However, hope may come from the detection of early stages of the disease and from the individualization of good prognosis factors, permitting the selection of patients for whom some curative therapies are in course of evaluation.

Diagnosis, Differential↗
PubMed2002

[Malignant pleural mesothelioma. Present data and perspectives for treatment].

CHEMOTHERAPY: With regard to the efficacy of mono-chemotherapy and according to the literature, no cytotoxic substance, apart from methrotrexate at high doses, leads to a response rate of more than 20%. With regard to cyrotoxic associations, the published results show slightly betterresponse rates. IMMUNOTHERAPY: Interleukine 2 as well as various interferons have been tested alone or in association with chemotherapy. Fairly encouraging response rates have been reported. However, the possibility of severe adverse events must be taken into account. RADIOTHERAPY: The interest of prophylactic parietal radiation following invasive thoracic treatment has been demonstrated. Palliative use of radiotherapy is possible for pain, and more rarely for decompression. With curative aim, the results of isolated radiotherapy are disappointing. SURGERY: Palliative surgery is aimed at reducing the tumour and pleural symphysis. Curative surgery consists in wide extrapleural pneumonectomy, permitting total resection of the visceral pleura, or decortication pleurectomy leaving the lung in place. Mean survival of patients having undergone surgery is of 10 to 17 months with rates between 10 and 30% at 2 years ASSOCIATED THERAPY: For the first time, despite high morbidity rates, associated therapy has led to prolonged survival, whereas isolated therapy has not. This is the case with an association of radical surgery, radiotherapy and adjuvant chemotherapy. IN THE FUTURE: In the treatment of malignant pleural mesothelioma, genetic, anti-proliferative and immune therapy, that attempt to use the immune system of the patient to obtain an anti-tumour cytotoxic reaction, appear promising.

Antimetabolites, Antineoplastic↗
PubMed2002

Phase I-II and pharmacokinetic study of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer and ovarian carcinoma.

BACKGROUND: The aim of this study was to determine the toxicity profile, the recommended dose (RD) and the pharmacokinetic parameters, and to evaluate the antitumor activity of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer (NSCLC) and ovarian carcinoma (OC). METHODS: Gemcitabine was administered as a 30-min infusion followed by a 2-h infusion of oxaliplatin, repeated every 2 weeks. Doses of gemcitabine and oxaliplatin ranged from 800 to 1500 and 70 to 100 mg/m(2), respectively. RESULTS: Forty-four patients (26 males, 18 females; median age 55 years) including 35 NSCLC (five platinum pretreated) and nine OC patients (all platinum pretreated) received a total of 355 cycles. All patients were evaluable for toxicity. No dose-limiting toxicity at any dose level occurred during the first two cycles; therefore, the highest dose-level of gemcitabine (1500 mg/m(2)) and oxaliplatin (85 mg/m(2)) was considered as the RD. Hematological toxicity was moderate amongst the 22 patients treated (167 cycles) at that dose level. Thirteen cycles were associated with grade 3-4 non-febrile neutropenia in six patients, and eight cycles with grade 3-4 thrombocytopenia in two patients. Other toxicities were mild to moderate, consisting of asthenia and peripheral neurotoxicity. Four of the 35 patients treated with oxaliplatin 85 mg/m(2) experienced grade 3 neurotoxicity requiring treatment discontinuation at cycle 10. In the range of the doses used, gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine appeared not to be affected by oxaliplatin 70-100 mg/m(2). Of the 44 patients evaluable for activity, 12 NSCLC patients experienced objective responses (one complete and 11 partial responses) and three OC patients showed tumor stabilization lasting for 6 months with a 50% decrease of CA 125 level. Two partial responses (NSCLC) and one tumor stabilization (OC) occurred in platinum-resistant patients. CONCLUSIONS: The combination of gemcitabine and oxaliplatin could be safely administered on an out-patient schedule in patients with advanced NSCLC and OC. The RD was gemcitabine 1500 mg/m(2) and oxaliplatin 85 mg/m(2) every 2 weeks. Promising antitumor activity was reported in patients with NSCLC and platinum-pretreated OC, and thus, deserves further evaluation.

Adenocarcinoma↗
PubMed2001

Carcinoma of an unknown primary site: a chemotherapy strategy based on histological differentiation--results of a prospective study.

BACKGROUND: To evaluate the efficacy and toxicity of a chemotherapy strategy based on histological differentiation, for patients with carcinoma of unknown primary site. PATIENTS AND METHODS: Forty-eight patients were prospectively included in the trial. Thirty patients with poorly-differentiated carcinoma or poorly-differentiated adenocarcinoma (group A) received a combination of cisplatin and etoposide. Patients with a responsive or stable disease after two cycles received the same regimen plus bleomycin, ifosfamide and G-CSF. Eighteen patients with well- or moderately-differentiated carcinoma (group B) received cisplatin, continuous infusion 5-fluorouracil (5-FU) and alpha-interferon. Treatment was maintained in case of response or stable disease for up to six cycles. RESULTS: The overall response rate (RR) for the entire group is 43% (95% confidence interval (CI): 35.9%-50.1%): seven CR and five PR in group A (RR = 40%) and six CR and two PR in group B (RR = 44%). Grade 4 leucopenia was observed in 22 (46%) patients and sepsis in 3 (6%). Median survival is 9.4 months (range 5-13.7 months) and 16.1 months (range 11.8 20.3 months), respectively. CONCLUSIONS: This chemotherapy strategy is one way to achieve high response rates, particularly for patients with well- or moderately-differentiated adenocarcinoma usually considered poorly chemosensitive.

Adenocarcinoma↗
PubMed2001

Impact of chromogranin A measurement in the work-up of neuroendocrine tumors.

Since the development of the first immunoassay for circulating chromogranin A in 1984, a lot of studies have evaluated its clinical impact in neuroendocrine tumors. Initially studied in pheochromocytoma patients, the clinical impact of chromogranin A has rapidly extended to most neuroendocrine tumours, sometimes in combination with other eutopic or ectopic secretions. In our experience, CgA demonstrates a variable sensitivity between NET primary and a high specificity. Our results suggest that CgA should be routinely screened in foregut-derived NET and abandoned in the routine screening of medullary thyroid carcinoma. In addition, in phaeochromocytoma and ileum-NET patients, CgA demonstrates a comparable sensitivity with urinary reference markers and its impact on the follow-up will form a key point when recommending routine screening. Both tumor burden and secretory activity should be taken into account when interpreting CgA results.

Biomarkers, Tumor↗
PubMed2000

Phase I and pharmacokinetic study of docetaxel and irinotecan in patients with advanced solid tumors.

PURPOSE: We conducted a phase I and pharmacokinetic study of docetaxel in combination with irinotecan to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the dose at which at least 50% of the patients experienced a DLT during the first cycle, and to evaluate the safety and pharmacokinetic profiles in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with only one prior chemotherapy treatment (without taxanes or topoisomerase I inhibitors) for advanced disease were included in the study. Docetaxel was administered as a 1-hour IV infusion after premedication with corticosteroids followed immediately by irinotecan as a 90-minute IV infusion, every 3 weeks. No hematologic growth factors were allowed. RESULTS: Forty patients were entered through the following seven dose levels (docetaxel/irinotecan): 40/140 mg/m(2), 50/175 mg/m(2), 60/210 mg/m(2), 60/250 mg/m(2), 60/275 mg/m(2), 60/300 mg/m(2), and 70/250 mg/m(2). Two hundred cycles were administered. Two MTDs were determined, 70/250 mg/m(2) and 60/300 mg/m(2); the DLTs were febrile neutropenia and diarrhea. Neutropenia was the main hematologic toxicity, with 85% of patients experiencing grade 4 neutropenia. Grade 3/4 nonhematologic toxicities in patients included late diarrhea (7.5%), asthenia (15.0%), febrile neutropenia (22.5%), infection (7.5%), and nausea (5.0%). Pharmacokinetics of both docetaxel and irinotecan were not modified with the administration schedule of this study. CONCLUSION: The recommended dose of docetaxel in combination with irinotecan is 60/275 mg/m(2), respectively. At this dose level, the safety profile is manageable. The activity of this combination should be evaluated in phase II studies in different tumor types.

Adult↗
PubMed2000

Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma.

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

Adult↗
PubMed2000

Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of the raltitrexed plus oxaliplatin combination regimen, to explore its safety and pharmacokinetics, and to assess its antitumor activity in patients with advanced solid tumors. PATIENTS AND METHODS: Forty-eight patients received the combination of raltitrexed plus oxaliplatin. Raltitrexed was administered as a 15-minute infusion followed by oxaliplatin as a 2-hour infusion 1 hour later, repeated every 3 weeks. Seven dose levels were explored, ranging from 2 to 3.75 mg/m(2) and from 85 to 130 mg/m(2) for raltitrexed and oxaliplatin, respectively. The pharmacokinetics of both raltitrexed and oxaliplatin was assessed at the last three dose levels. RESULTS: Forty-six patients were assessable for toxicity. Severe toxicities usually occurred from dose level V (raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2)). This combination was not myelosuppressive, eliciting only sporadic grades 3 and 4 neutropenia and/or thrombocytopenia without complications. There was no alopecia. DLTs were asthenia and nausea/vomiting, despite systematic antiemetic prophylaxis. Dose level VI (raltitrexed 3.5 mg/m(2) and oxaliplatin 130 mg/m(2)) was deemed to be the MTD. Eight confirmed partial responses were observed: six patients with malignant mesothelioma (both pretreated and nonpretreated), one with fluorouracil-refractory pancreatic carcinoma, and one with renal carcinoma. Evaluation of the pharmacokinetics of both drugs did not suggest any drug interaction. CONCLUSION: The combination of raltitrexed and oxaliplatin given as consecutive short infusions every 3 weeks seems to be an acceptable regimen that allows a dose-intensity as high as the sum of the recommended doses of each agent given alone. The dose recommended for further phase II studies is raltitrexed 3 mg/m(2) and oxaliplatin 130 mg/m(2) every 3 weeks. Promising antitumor activity has been observed in patients with malignant mesothelioma.

Adult↗