PubMed Health⌕ Search

Biomedical subjects

C Louvet

Publications and source records attributed to C Louvet.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Adenocarcinoma of the pancreas. General characteristics].

EPIDEMIOLOGY: Pancreatic carcinoma ranks fifth among the leading causes of cancer death in developed countries. Although the incidence of pancreatic cancer is about 10 per 100,000 inhabitants, the five-year overall survival is barely one to 4%. Few risk factors have been identified. Smoking increases the relative risk by 1.5, chronic pancreatitis by 26. Hereditary formes are rare. PATHOLOGY AND MOLECULAR ABNORMALITIES: Adenocarcinomas of the ductal phenotype represents about 90% of the pancreatic tumors. Seventy percent of adenocarcinomas are located in the head. Mutations of K-ras oncogene and p53 anti-oncogene are noted, respectively, in 80 to 90% and 70% of the ductal adenocarcinomas. The mutation of p53 is associated with a poor prognosis. Certain less frequent forms such as mucinous cystadenocarcinomas, or intraductal papillary-mucinous tumors seem to have a better prognosis. However, this is not true for acinar cell carcinomas responsible for various paraneoplastic syndromes. PATTERN OF SPREAD: The disease arises in the ductal epithelium and rapidly spreads to regional lymph nodes and the liver. At diagnosis, nodal involvement is found in 80% of cases. Half of the patients have detectable visceral metastasis with a median survival of three to six months. Among the remaining non metastatic patients, approximately one in 5 has undetected peritonal carcinomatosis. Only 10 to 20% of the patients undergo surgical complete resection with a median survival of 15 to 19 months.

Adenocarcinoma↗
PubMed1998

[Adenocarcinoma of the pancreas. Diagnosis and evaluation].

SYMPTOMS: Pain, jaundice, or weight loss are the presenting features of 90% of the cases. Patients with tumors of the body or the tail of the pancreas do not rapidly develop jaundice. Therefore, their diagnosis is delayed and metastasis are more frequently detected at diagnosis. RADIOLOGIC DIAGNOSIS: The diagnosis may be established by ultrasonography, endoscopic ultrasonography and most importantly by CT scan with helicoidal continuous acquisition and contrast injection. However, these methods do not efficiently detect tumors smaller than 2 cm or with only superficial peritoneal involvement. Laparoscopy and angiography are used less and less frequently to evaluate resectability. The diagnostic work-up with CT scanning is able to anticipate resectability in 50 to 90% of the cases. PATHOLOGY: Histopathology must be obtained since 10% of the pancreatic carcinoma are not of the ductal type and not all pancreatic tumors are malignant. When a pathological specimen cannot be obtained during surgery, a cytology specimen may be obtained with a fine needle guided by CT scan. PROGNOSIS: Survival depends on the possibility of a complete resection of the tumor. If complete resection is obtained, the prognostic factors are in decreasing importance: tumor size, lymphatic and vascular involvement, and invasion of peri-pancreatic tissues.

Adenocarcinoma↗
PubMed1998

[Adenocarcinoma of the pancreas. Therapeutic strategies].

SURGERY: Surgery whether curative or palliative, is the major modality of treatment. A complete resection is possible in about 20% of patients with a median survival of 12 to 16 months and a 20% five year survival. After complete resection 70 to 80% of patients develop a local recurrence. Biliary and gastro-intestinal bypasses as well as antalgic techniques are useful palliative procedures. ADJUVANT AND NEOADJUVANT TREATMENT: Chemoradiotherapy is used either as adjuvant or neoadjuvant treatment. External beam irradiation techniques are used to deliver 45 to 50 Gy to the pancreas in five to six weeks. Concomitant fluorouracil is administered in bolus injections or better in continuous infusion,, either alone or in association with cisplatinum. Chemoradiotherapy reduces the local relapse rate and slightly, though significantly, increases the median survival. Therefore, after chemoradiotherapy, metastatic spread becomes the major cause of death. PALLIATIVE TREATMENT: For locally advanced diseases, chemoradiotherapy has a true palliative effect with acceptable toxicity. Metastatic disease remains a challenge. Fluorouracil based chemotherapy with or without cisplatinum occasionally obtains effective palliation. Among new agents, only gemcitabine has proven clinical activity associated with low toxicity and is practical to use. THERAPEUTIC STRATEGY: Presently, patients with resectable pancreatic carcinoma should be included in a prospective trial to receive combined modality treatment with adjuvant or neo-adjuvant chemoradiotherapy. The choice of treatment for patients with locally advanced or metastatic disease, should be based on the possibility of assuring a satisfactory quality of life. Present research should progress through controlled clinical trials to study original systemic treatment and combined modalities able to produce a lasting local control.

Adenocarcinoma↗
PubMed1998

[Tumoral angiogenesis: physiopathology, prognostic value and therapeutic perspectives].

INTRODUCTION: Angiogenesis activation plays a crucial role in tumoral growth and metastases dissemination. This review summarizes and analyzes current knowledge on molecular mechanisms related to angiogenesis and the prognostic value of its effectors. It also focuses on the therapeutical relevance of various drugs that might inhibit angiogenesic processes. CURRENT KNOWLEDGE AND KEY POINTS: Tumor angiogenesis involves complex interactions between tumoral, stromal, endothelial cells, fibroblasts and the extracellular matrix. Normal and malignant angiogenesis depends on the balance of proangiogenic and antiangiogenic factors. Endothelial cells are activated by growth factors, such as Vascular Endothelial Growth Factor (VEGF), and proliferate; they release proteases able to induce degradation of the basement membrane and extracellular matrix, and undergo migration and tubulogenesis. Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models. Assessment of intratumoral microvessel density and quantification of angiogenic factors, including VEGF, are of prognostic value in most cancers, particularly in breast cancer. However, the use of these prognosis markers in clinical practice is still controversial due to the lack of prospective studies and to technical limits inherent to the scoring and standardization of immunohistochemical methods. FUTURE PROSPECTS AND PROJECTS: Better understanding of the molecular basis of angiogenesis allows the development of new therapeutical strategies. Biochemical targets of antiangiogenic therapy are: the interaction between angiogenic factors and their receptors; the interaction of endothelial cells with the extracellular matrix; and intracellular signaling pathways. Angiogenesis inhibitors may not cause tumor regression, but inhibit cellular growth and produce "disease dormancy". Extensive phase I to III clinical trials involving antiangiogenesis therapy are in progress.

Angiogenesis Inducing Agents↗
PubMed1998

A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer: evolution of a regimen. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

The addition of leucovorin (LV) to 5-fluorouracil (5-FU) in advanced colorectal cancer has shown improved tumour response rates in many trials, but the optimal LV/5-FU regimen has yet to be determined. Seven studies carried out over the last 12 years to evaluate the safety and efficacy of various LV/5-FU regimens are reviewed. The initial bimonthly high-dose LV/5-FU regimen consisted of high-dose LV as a 2-h infusion followed by 5-FU as an intravenous (i.v.) bolus plus a 22-h continuous infusion (CI), repeated for two consecutive days every 2 weeks. A randomised comparison of this bimonthly high-dose LV/5-FU regimen and the NCCTG-Mayo Clinic regimen (LV [20 mg/m2/day] followed by 5-FU bolus [425 mg/m2/day] daily x 5, every 4 weeks) showed that the bimonthly high-dose LV/5-FU regimen was superior to the NCCTG-Mayo Clinic regimen in response rate and progression-free survival, but showed no difference in overall survival. In addition, toxicity was less with the bimonthly high-dose LV/5-FU regimen. These promising results led to a phase II trial of a simplified bimonthly high-dose LV/5-FU regimen consisting of LV (500 mg/m2/day) and a 48-h CI of 5-FU (1.5-2 g/m2/day) which has been administered alone or in combination. In summary, GERCOD-sponsored studies have further demonstrated that high doses of both LV and 5-FU given as a CI can improve response rates still more with acceptable toxicity. Further studies are focused on the effectiveness of combination with oxaliplatin or CPT-11 in metastatic disease and the use of high-dose LV/5-FU regimens for colorectal cancer in the adjuvant setting.

Antidotes↗
PubMed1998

Bimonthly high-dose leucovorin, 5-fluorouracil infusion and oxaliplatin (FOLFOX3) for metastatic colorectal cancer resistant to the same leucovorin and 5-fluorouracil regimen.

BACKGROUND: FOLFOX2, a bimonthly regimen of high-dose leucovorin (LV), 48-hour continuous infusion of 5-fluorouracil (5-FU) (LV-5-FU) and oxaliplatin (100 mg/m2) produced a high response rate (46%; 95% confidence interval (95% CI): 31%-60%) in 5-FU pre-treated patients with metastatic colorectal cancer. In this phase II study, pre-treated patients were given a lower dose of oxaliplatin to reduce the toxic effects of the regimen. PATIENTS AND METHODS: Thirty patients with advanced colorectal adenocarcinoma and progression while receiving bimonthly LV-5-FU (LV: 500 mg/m2, 5-FU: 1.5-2 g/m2/22 hours, days 1-2, every two weeks), were given the same LV-5-FU schedule with the addition of oxaliplatin (85 mg/m2) every two weeks (FOLFOX3). RESULTS: The main toxic effects were peripheral neuropathy (90%) with four severe sensitive neuropathies (WHO grade 2: 13%). The response rate was 20% (95% CI: 8%-39%). Median progression-free survival was 26 weeks, median survival was 57 weeks from the start of FOLFOX3 and median duration of the response was 37 weeks. CONCLUSIONS: Results obtained with FOLFOX3 confirmed the synergy between oxaliplatin and 5-FU in 5-FU-resistant metastatic colorectal cancer. However, the response rate seems to be lower than that obtained with FOLFOX2. Further studies to determine the best oxaliplatin dose intensity are in progress.

Adenocarcinoma↗
PubMed1998

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Adult↗
PubMed1998

Oxaliplatin for the treatment of advanced colorectal cancer: future directions.

The introduction of oxaliplatin into the colorectal cancer setting represents a significant advancement in the treatment of the disease. Synergistic effects with traditional therapy 5-fluorouracil/folinic acid have increased response rates significantly, improved time-sensitive response parameters, and facilitated the removal of previously unresectable hepatic metastases, thus changing the natural history of the disease. Ongoing and planned trials are identifying various issues that need to be addressed to fully realize the potential of oxaliplatin. These include optimization of dosing and schedule of administration, determination of the most effective oxaliplatin-5-fluorouracil/folinic acid combination, definition of the role of new thymidylate synthase inhibitors with respect to oxaliplatin therapy, and identification of the most effective combinations of oxaliplatin with the new anticancer agents that have been recently introduced. Providing the answers to these questions will contribute to changing the attitude of the clinical oncologist regarding what strategy to adopt in treating colorectal cancer in the coming years.

Antineoplastic Agents↗
PubMed1998

[What's new in adjuvant therapy of colorectal cancers?].

The indication for adjuvant chemotherapy after macroscopically complete resection of a colonic cancer with lymph node involvement (Dukes C or stage III) is now established. Ongoing studies are designed to define the optimal modalities. A 6-month postoperative treatment based on 5-FU modulated by folinic acid currently represents standard treatment, as conventional treatment with 5-FU and Levamisole for one year is more constraining, potentially more toxic and not more effective. No published study has yet demonstrated any significant benefit of adjuvant chemotherapy for forms B2 or II, essentially because of a lack of statistical power. The place of local treatment and specific immunotherapy is currently being investigated. In the short- or medium-term, the development of new drugs active in the metastatic setting, as well as genetic prognostic factors, should modify current attitudes concerning indications and modalities of adjuvant chemotherapy for colonic cancers.

Adjuvants, Immunologic↗
PubMed1997

Bimonthly high dose leucovorin and 5-fluorouracil 48-hour infusion with interferon-alpha-2a in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

UNLABELLED: BACKGROUND; The rationale for the modulation of 5-fluorouracil (5-FU) with interferon-alpha (IFN) is inhibition of 5-FU catabolism and 5-FU resistance. Clinical trials have shown debatable results when IFN is given in high doses with 5-FU used as a bolus alone or in combination with leucovorin (LV). A first-line Phase II study was performed in 50 patients with metastatic colorectal carcinoma who were given a bimonthly combination of high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN. METHODS: The regimen was comprised of a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days, and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours, starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. IFN was administered subcutaneously three times weekly at a dose of 3 MU (body surface area [BSA] < 1.75 m2) or 4.5 MU (BSA > OR = 1.75 m2). RESULTS: World Health Organization toxicity Grade 3-4 occurred in 21 patients (42%): diarrhea in 6%, mucositis in 12%, neutropenia in 30%, and alopecia in 8%. The overall response rate was 44%; 1 patient had a complete response (2%), 21 had partial responses (42%), 23 had stable disease (46%), and 5 had disease progression (10%). The median progression free survival was 9 months, and median survival was 25 months. CONCLUSIONS: Bimonthly high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN had good activity in patients with advanced colorectal carcinoma. However, as in other schedules of LV and 5-FU, IFN induces high grade toxicity.

Adenocarcinoma↗
PubMed1997

Bimonthly high dose leucovorin and 5-fluorouracil 48-hour continuous infusion in patients with advanced colorectal carcinoma. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

BACKGROUND: It has been suggested that there is a relationship between 5-fluorouracil (5-FU) dose levels and response rates. A bimonthly 2-day regimen of leucovorin (LV) and 5-FU bolus plus infusion has been found to be superior to a monthly 5-FU bolus with low dose LV. Based on these reports, a first-line Phase II study was performed in 101 patients with advanced colorectal carcinoma who were given a bimonthly combination of high dose LV and a high dose 48-hour infusion of 5-FU. METHODS: The selected regimen included a 2-hour infusion of LV, 500 mg/m2, on each of 2 consecutive days and a 48-hour infusion of 5-FU, 1.5 to 2 g/m2/24 hours starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. Evaluation was performed every six cycles. This study reports the treatment of 101 patients with measurable disease. RESULTS: World Health Organization toxicity Grade 3-4 occurred in 15% of patients, nausea in 2%, diarrhea in 5.1%, mucositis in 4%, neutropenia in 4% (Grade 4: 2%), hand-foot syndrome in 2%, alopecia in 4%, and encephalopathy in 1%. The overall response rate was 33.7%. Five patients had a complete response (5%), and 29 had a partial response (28.7%). In 45 patients disease was stable (44.6%), and in 19 patients there was disease progression (18.8%). Three patients (3%) could not be evaluated. The median progression free survival was 8 months and median survival was 18 months. CONCLUSIONS: In the current study, bimonthly high dose LV and a high dose 48-hour infusion of 5-FU had activity in patients with advanced colorectal carcinoma. Toxicity is notably low, and the regimen is suitable for use in combination with other drugs.

Adenocarcinoma↗
PubMed1997

[Role and value of oxaliplatin in metastatic colorectal cancers].

Oxaliplatin is a new cytotoxic drug, with a mechanism of action nearly similar to that of cisplatin. However, in vitro and in vivo studies showed an interesting activity in colorectal cancer. This article summarizes the main data available for patients with advanced colorectal cancer concerning phase I studies, pharmacokinetic, single agent phase II studies, combinations with 5-fluorouracil (5-FU), and tolerance. 10% response rate in second-line therapy, 20 to 25% in first-line, and 26 to 45% in combination with 5-FU in second-line have been reported. The limiting toxicity is a reversible sensitive neuropathy. Oxaliplatin combined with 5-FU should be considered as one of the best therapeutic options in second-line colorectal cancer patients. Further studies will indicate the role of oxaliplatin in less advanced disease, such as metastatic first-line or adjuvant therapy.

Antineoplastic Agents↗
PubMed1997

[Modulation of 5-fluorouracil with folinic acid in advanced colorectal cancers. Groupe d'étude et de recherche sur les cancers de l'ovaire et digestifs (GERCOD)].

The rational of leucovorin modulation of 5-fluorouracil and the clinical results in colorectal cancer are reviewed with special emphasis on the monthly schedule of low dose leucovorin and 5FU bolus for 5 consecutive days (NCCTG-Mayo Clinic regimen) and the bimonthly schedule of high-dose leucovorin and 5FU bolus plus continuous infusion for two consecutive days (LV5FU2) which is now considered as a new standard.

Antidotes↗
PubMed1997

[Large granular T-cell lymphocytic leukemia disclosed by bilateral uveitis: association with celiac disease].

A 70-year-old woman presented with bilateral anterior uveitis. She was on a gluten-free diet because of a celiac disease which had been diagnosed 3 months before. An anterior chamber aspirate contained a majority of large granular lymphocytes (LGL). The investigation of a chronic neutropenia led to the diagnosis of an otherwise typical T-LGL leukemia. This seems to be the first report of a CD3+ CD4- CD8+ T-LGL leukemia causing anterior uveitis through infiltration of leukemic cells, and the second report of an intriguing association of celiac disease with T-LGL leukemia.

Aged↗
PubMed1997

[Oxaliplatin, folinic acid and 5-fluorouracil (folfox) in pretreated patients with metastatic advanced cancer. The GERCOD].

Preliminary studies suggest synergy between oxaliplatin and fluorouracil (5-FU). To assess this issue, we performed a study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. Regimen consisted of oxaliplatin day 1, 130 mg/m2 every two cycles (folfox 1) or 100 mg/m2/cycle (folfox 2) or 85 mg/m2/cycle (folfox 3) and leucovorin 500 mg/m2 as a 2-hour infusion, followed by 5-FU 22 h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. One hundred and thirteen patients have been treated. One complete response (CR) and 32 partial responses (PRs) were observed for an overall response rate of 29.2%. Sixty-seven patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU than the one used in the folfox regimens, among them 18 had PRs (26.9%). The best response rate was observed in patients treated with the folfox 2 regimen: 41.7%. From start of folfox, median progression-free survival was 6 months and median survival 13 months. Limiting toxicities were peripheral neuropathy and neutropenia. Fifty-four percent of the patients experienced WHO toxicity > or = grade 3 with the folfox1 regimen, 45% with the folfox2 and 40% with the folfox3. The folfox regimens achieve a high response rate in pretreated patients with CRC. Further studies are needed to determine the best oxaliplatin dose-intensity.

Adult↗
PubMed1997

Long-term follow-up after adjuvant chemotherapy in completely resected early stage ovarian carcinoma.

OBJECTIVE: To evaluate the impact of standardized staging, surgery and adjuvant chemotherapy on survival of patients with completely resected early ovarian carcinoma. STUDY DESIGN: We performed a multicentric retrospective analysis of 283 patients with early stage ovarian carcinoma consecutively treated between 1977 and 1993. Borderline tumours were excluded. A comprehensive staging was performed during initial laparotomy. Patients were treated by standardized surgical resection and all excepted stage IA received a 6-course adjuvant chemotherapy. RESULTS: Eighty patients were excluded because of incorrect substaging, inadequate surgery and adjuvant therapy. The analysis was performed on 203 patients with completely resected early stage ovarian cancer (139, stage I; 64, stage II). Relapse-free survival and overall survival rates for stage I were 66 and 69%, respectively. Relapse-free survival and overall survival rates for stage II were 57 and 61% respectively. Median time of relapse was 18 months (range, 1-107 months). Sites of relapse were peritoneum (45%), retroperitoneal lymph nodes (37%) and distant metastases (18%). Relapses occurring within 18 months had a median survival after relapse of 9 months while later relapses had a median survival of 22 months (P = 0.005). There was no significant difference in relapse-free and overall survival according to the age, performance status and pathology. Cisplatin-based chemotherapy improved the 10-year overall survival of patients with stage IIB and IIC as compared to chemotherapy without cisplatin (oral melphalan. CMF regimen); 91 vs. 33% (P = 0.012) and 75 vs. 42% (P = 0.05), respectively. Cisplatin-based regimens did not improve survival in stage IA, IB and IIA. CONCLUSIONS: Early ovarian cancers have a good prognosis after comprehensive staging, complete surgery and adjuvant chemotherapy. Cisplatin-based regimens compared to melphalan and CMF showed a significant increase of survival in stage IIB and IIC. Prognosis of relapse depends on the relapse-free interval duration.

Adult↗