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Biomedical subjects

P Rougier

Publications and source records attributed to P Rougier.

At least 19 recordsLinked to original sources
PubMed2001

Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis (PC) is fatal, despite standard systemic chemotherapy. A new approach that combines maximal surgery with maximal regional chemotherapy has potential to cure selected patients who have colorectal PC. The authors have reported the oncologic results of this combined treatment. METHODS: The authors performed a retrospective study of 64 patients who had PC arising from colorectal adenocarcinomas, 19 (29.6%) of whom also had other metastases. These patients were treated by complete resection of all detectable tumors and by a 5-day course of early intraperitoneal chemotherapy (EPIC) with mitomycin C, then by 5-fluorouracil (n = 37), or by intraoperative intraperitoneal chemohyperthermia (IPCH) with mitomycin C, alone or combined with cisplatin (n = 27), in 2 separate trials. In the trial of IPCH, aimed at selecting the most reliable procedure in terms of spatial diffusion and thermal homogeneity, the 27 patients were treated with 7 different procedures. The extent of PC was assessed precisely by using a peritoneal index. The median follow-up period for the entire patient population was 51.7 months. RESULTS: The postoperative mortality and morbidity rates were 9.3% and 54.6%, respectively. Most severe complications occurred in patients who required extensive cytoreductive surgery. Global and disease-free survival rates were respectively 60.1% and 54.7% at 2 years and were 27.4% and 18.4% at 5 years. Results were significantly better (P = 0.04) when patients were metastasis-free (apart from PC) and when the peritoneal index was lower than 16 (P = 0.005). IPCH seemed to be more effective than EPIC for treatment of PC. CONCLUSION: This treatment plan, which combined maximal surgery with maximal regional chemotherapy, cured approximately 25% of patients. This strategy was mainly applicable to patients with limited intraperitoneal cancer volume and no extraperitoneal involvement. IPCH proved to be more effective than EPIC but more difficult to use correctly. Future results should improve through routine use of the optimal hyperthermia procedure, with improvements in the composition of instillate, better patient selection, and the reduction in the rate of complications that occurs with physician experience.

Adolescent↗
PubMed2001

Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours.

A few studies have suggested an antitumour activity of somatostatin analogues in neuroendocrine tumours (NET). The aim of this study was to evaluate the antitumour efficacy of somatostatin analogues in patients with documented progressive tumours. 35 consecutive patients with documented tumour progression were treated with somatostatin analogues. Patients were classified into two groups. In Group 1, tumours were progressing rapidly (an increase of 50% or more in the lesion surface area in 3 months) and in Group 2, tumours were progressing more slowly (an increase of less than 50% in the lesion surface area in 3 months but greater than 25% in 6 months). Treatment consisted of subcutaneous (s.c.) octreotide, 100 microg thrice daily for 17 patients, intramuscular lanreotide, 30 mg/every 14 days for 11 patients and for 7 patients both somatostatin analogues were used successively during the follow-up. Primary tumour sites were the small intestine (n=12), pancreas (n=13), lungs (n=5), and other sites (n=5). 18 patients had the carcinoid syndrome with flushing and/or diarrhoea. The median duration of treatment was 7 months. Treatment was discontinued in 3 patients due to side-effects. One patient (3%) achieved a partial response and the disease was stabilised in 20 patients (57%) for a median duration of 11 months (6-48 months). Stabilisation of patients in Group 1 was significantly less frequent at 6 months than that of patients in Group 2 (4/12 and 13/17 respectively, P<0.02). Somatostatin analogue treatment resulted in one partial response (3%) and 20 cases of stabilisation (57%) in 35 patients with progressive NET. A slow tumour growth rate before treatment is predictive of a good response to somatostatin analogues which could be considered an option for first-line treatment.

Adult↗
PubMed2001

The treatment of undifferentiated neuroendocrine tumors.

The aggressiveness of poorly-differentiated neuroendocrine tumors is similar to small-cell lung cancer within a median survival of 6 months without treatment. Most patients have metastatic disease and poor condition at the time of diagnosis, and cannot be approached surgically with curative intent. Moertel et al. [Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin, Cancer 1991;68:227--232] reported an objective response rate of 67% with a chemotherapy regimen combining etoposide plus cisplatin, with a median survival of 19 months and a median time to progression of 11 months. Since this publication, this regimen has been considered as the reference treatment for poorly-differentiated neuroendocrine tumors. A French retrospective study has recently confirmed the high chemosensitivity of those tumors. However, the prognosis remains poor with a 2-year survival lower than 20% and other therapeutic approaches should be developed.

Adult↗
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

Adaptative effects of loss of vision on upright undisturbed stance.

In order to evaluate the long term effect of blindness on an undisturbed postural task, seven blind individuals (BLI) were compared to twelve healthy individuals (REF) who were required to close their eyes. To this aim, centre of pressure (CP) trajectories were recorded through a force platform on which the subjects remained upright. Through a low-pass filter, the vertical projection of the centre of gravity (CG(v)) and consequently the difference CP-CG(v) were estimated. The former represents the controlled variable whilst the latter is assumed to express the resultant joint stiffness. A first analysis consisted in studying the frequency distribution of these motions. Increased mean amplitudes in both elementary motions and no difference between frequency distributions were observed for the BLI when compared to the REF group. These trajectories were then modelled as a fractional Brownian motion process in order to gain insight about the nature of the control mechanisms called into play and their spatio-temporal organisation. Moreover, the main characteristic observed in the BLI group is a decreased in CP-CG(v) motions, which, according to Winter's model, may be related to joint stiffness. In addition, reduced spatial transition point co-ordinates and more deterministic control mechanisms aimed at returning the estimated CG to an equilibrium point during the longest Deltat were observed. This phenomenon is more pronounced in the antero-posterior direction and also allows the blind subject to significantly diminish their CG sways. Finally, these features are discussed in relation to other similarly analysed investigations.

Adult↗
PubMed2000

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer. METHODS: 387 patients previously untreated with chemotherapy (other than adjuvant) for advanced colorectal cancer were randomly assigned open-label irinotecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infusion schedules were once weekly or every 2 weeks, and were chosen by each centre. We assessed response rates and time to progression, and also response duration, survival, and quality of life. Analyses were done on the intention-to-treat population and on evaluable patients. FINDINGS: The response rate was significantly higher in patients in the irinotecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 for evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to progression was significantly longer in the irinotecan group than in the no-irinotecan group (median 6.7 vs 4.4 months, p<0.001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in the no-irinotecan group, but effects were predictible, reversible, non-cumulative, and manageable. INTERPRETATION: Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life. This combination should be considered as a reference first-line treatment for metastatic colorectal cancer.

Adenocarcinoma↗
PubMed2000

A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma.

The aim of this study was to evaluate the efficacy of docetaxel as first-line chemotherapy in patients with unresectable metastatic or locally advanced pancreatic adenocarcinoma and to further characterise the safety and pharmacokinetic profiles of docetaxel. 43 patients were enrolled into this phase II study. Treatment consisted of a 1-h infusion of docetaxel 100 mg/m2 every 3 weeks without premedication with corticosteroids until progression or unacceptable toxicity occurred. Dose modifications were planned for adverse events. Patients were observed for 1 month after the last docetaxel infusion, to document any late adverse events, with a follow-up every 3 months until death. Response rate and duration were the major efficacy endpoints. Response status was reviewed by an external independent panel. Pharmacokinetic analysis was performed during the first treatment cycle. 40 patients were evaluable for response, and all were evaluable for safety. After independent review, partial response was recorded in 6 patients (overall response rate, 15%; 95% confidence limit (CI), 7.7-29.8%) and stable disease was recorded in 15 patients (38%). The median duration of response was 5.1 months (range: 3.1-7.2). The median pain control time was 4.5 months (range: 0-8) and the median time to performance status worsening was 2.3 months (range: 0-4.5). Most patients 40 (93.0%) received a relative dose intensity of more than 70% of the planned dose. The incidence and severity of adverse events reflected the known safety profile for docetaxel. Docetaxel clearance was reduced in patients with elevated concentrations of hepatic enzymes or bilirubin. Docetaxel is an active agent for unresectable metastatic or locally advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2000

New directions in the treatment of colorectal cancer: a look to the future.

Today, adjuvant 5-fluorouracil based therapy is known to significantly reduce the relapse rates and the risks of dying from resected colon cancer; chemotherapy approximately doubles overall survival of advanced colorectal cancer and second line treatment prolongs the survival of patients compared with best supportive care. At the molecular level a number of key genes are often mutated in cancer of the colon and some of these key regulators of apoptosis are discussed (p53 and bcl-2 family of proteins). Dihydropyrimidine dehydrogenase (DPD) activity may be a potential factor controlling fluorouracil (FU) responsiveness at the tumoral level and its importance is stressed. The rationale of combining FU with DPD inhibitors is fairly strong. Ethynyluracil, UFT and S1 pursue this strategy while capecitabine has another the rationale. Drug resistance should be at least partially overcome by combination chemotherapy (FU plus mitomycin, oxaliplatin, irinotecan) and combined modality (FU+RT) regimens. Improved surgical techniques and radiotherapy have substantially decreased local failure rates for rectal cancers. Finally, innovative treatment modalities such as anti-angiogenetic and antimetastatic agents, farnesyl transferase inhibitors, vaccine and gene therapy are in early clinical trials.

Antimetabolites, Antineoplastic↗
PubMed2000

Extensive molecular screening for hereditary non-polyposis colorectal cancer.

The genetic abnormalities underlying hereditary non-polyposis colorectal cancer (HNPCC) are germline mutations in one of five DNA mismatch repair genes or in the TGFbetaRII gene. The aim of our study was to evaluate the significance of simple tests performed on tumours to select appropriate candidates for germline mutational analysis. We studied three groups of patients, HNPCC kindreds fulfilling the International Collaborative Group (ICG) criteria (n = 10), families in which at least one of the criteria was not satisfied (n = 7) and sporadic colorectal cancer (CRC) diagnosed before the age of 50 (n = 17). We searched for microsatellite instability (MSI), presence of hMSH2 and hMLH1 germline mutations, expression of hMSH2, hMLH1 and p53 proteins in tumoural tissue samples by immunostaining. Fifteen out of 17 (88%) of HNPCC and incomplete HNPCC cases were MSI and eight pathogenic germline mutations in hMSH2 or hMLH1 were detected in these two groups (53%). All the 17 early-onset sporadic cases were MSS and no germline mutations were detected among the seven investigated cases. Thirteen out of 15 (81%) familial cases were MSI and p53 protein-negative, whereas 13/14 (93%) sporadic cases were MSS and strongly p53 protein-positive. This extensive molecular investigation shows that simple tests such as MS study combined with hMSH2 and hMLH1 protein immunostaining performed on tumoural tissues may provide valuable information to distinguish between familial, and probably hereditary, and sporadic CRC cases.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups.

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P<0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P< or =0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs.

Adult↗
PubMed2000

Center of gravity motions and ankle joint stiffness control in upright undisturbed stance modeled through a fractional Brownian motion framework.

The authors modeled the center of gravity vertical projection (CG(v)) and the difference, CP - CG(v), which, combined, constitute the center of pressure (CP) trajectory, as fractional Brownian motion in order to investigate their relative contributions and their spatiotemporal articulation. The results demonstrated that CG(v) and CP - CG(v) motions are both endowed in complementary fashion with strong stochastic and part-deterministic behaviors. In addition, if the temporal coordinates remain similar for all 3 trajectories by definition, the switch between the successive control mechanisms appears for shorter displacements for CP - CG(v) and CG(v) than for CP trajectories. Results deduced from both input (CG(v)) and muscular stiffness (CP - CG(v)) thus provide insight into the way the central nervous system regulates stance control and in particular how CG and CP - CG are controlled.

Adult↗
PubMed2000

Randomized comparison of prophylactic antidiarrheal treatment versus no prophylactic antidiarrheal treatment in patients receiving CPT-11 (irinotecan) for advanced 5-FU-resistant colorectal cancer: an open-label multicenter phase II study.

Delayed diarrhea is the main toxicity of irinotecan at the currently recommended dose of 350 mg/m2 30-minute intravenous infusion, once every 3 weeks. This phase II, multicenter, open-label, randomized study was primarily designed to evaluate the effect of a 15-day Tiorfan (racecadotril) treatment on the incidence and severity of irinotecan-induced delayed diarrhea. One hundred thirty-six patients with metastatic colorectal cancer who failed to respond to a 5-fluorouracil-based treatment received 714 cycles of irinotecan. The patients were randomly allocated either to group A (68 patients) and received Tiorfan (300 mg/day) from D0 to D15 or to group B (68 patients) with no prophylactic treatment. Delayed diarrhea occurred in 197 of 355 cycles (55%) in Group A and 203 of 344 cycles (59%) in Group B. grade III-IV diarrhea was reported in 17 of 40 compliant patients (42%) in group A and 31 of 68 evaluable patients (45%) in group B. No difference was observed between the two groups for delayed diarrhea characteristics, incidence, or severity. The response rate in 99 evaluable patients was 12.1% (6.4%-20.2%). This study has shown that Tiorfan given prophylactically at 300 mg/day has no effect on delayed diarrhea.

Adult↗
PubMed2000

The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors.

OBJECTIVE: Somatostatin analogs are the first-line drugs for controlling hormone-mediated symptoms of carcinoid tumors. Prospective and retrospective studies have suggested that somatostatin analogs also have antiproliferative activity. The octapeptide lanreotide is available in sustained-release form, obviating the need for daily injections. METHODS: A total of 46 patients were enrolled in this open, prospective, phase II trial. They received lanreotide 30 mg i.m. every 14 days for 6 months when they had symptomatic carcinoid tumors, and lanreotide 30 mg i.m. every 10 days if they had nonsymptomatic tumors. Nonsymptomatic tumors were progressive before the start of the study. Tumor size was assessed every 3 months by means of computed tomography. The assessment was centralized and was made by an external panel. RESULTS: In all, 30 patients had symptomatic neuroendocrine tumors and 16 had asymptomatic neuroendocrine tumors. Five patients in the group with symptomatic tumors and two in the group with nonsymptomatic tumors were considered not to be evaluable. The mean duration of treatment was 12 months in the group with symptomatic tumors and 13 months in the other group. Among the 39 evaluable patients, two objective responses were obtained, giving an objective response rate of 5% (one in the group with symptomatic tumors and one in the other group). Nineteen patients had no significant increase in their tumor size for a mean of 9.5 months. CONCLUSIONS: Lanreotide is safe and well tolerated in patients with carcinoid tumors. It seems to have both symptomatic and antitumoral effects in this setting.

Antineoplastic Agents↗
PubMed2000

Chemotherapy in the treatment of neuroendocrine malignant tumors.

The efficacy of chemotherapy in digestive neuroendocrine tumors (NET) depends on primary site and histological differentiation. Many reports have suggested a superior activity of chemotherapy for pancreatic NET than for metastatic carcinoid tumors with response rates ranging from 40 to 60% compared to 20%. The standard chemotherapy for pancreatic NET is a combination of adriamycin and streptozocin and to a lesser extent a combination of 5FU and streptozocin. In contrast, there is no clear standard chemotherapy for carcinoid tumors and if most oncologists use a combination of 5FU and streptozocin in the case of advanced, progressive and nonresectable carcinoid tumors, the results are mostly poor and the benefit seldom counterbalances its toxicity. In these carcinoid tumors the combination of hepatic artery ischemia alternating with chemotherapy has given impressive results in one study, which, however, have never been confirmed. Tumor cell differentiation is a major prognostic factor and some reports have suggested a higher chemosensitivity for undifferentiated or poorly differentiated NET with tumor response rates ranging from 41 to 69% when a VP16-CDDP combination is used. This chemosensitivity is, unfortunately, as in small cell lung carcinomas, of short duration. Related to this special problem and the number of other active treatments in NET, the place of chemotherapy always has to be discussed in a multidisciplinary fashion. Surgical excision, chemoembolization, interferons and somatostatin analogues have to be emphasized and eventually combined with chemotherapy, especially in slowly growing tumors. New active chemotherapy regimens have to be tested clearly in this orphan group of tumors which does not hold much interest to the pharmaceutical companies.

Antineoplastic Combined Chemotherapy Protocols↗