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Biomedical subjects

M Ducreux

Publications and source records attributed to M Ducreux.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2001

[Prevention and treatment of chemotherapy-induced digestive toxicities].

Digestive complications are frequent dose-limiting side-effects of chemotherapy. The incidence and the severity of these toxicities have to be systematically evaluated in order to provide specific curative and preventive treatments. Quick resolution of these complications is important to improve quality of life, and also to prevent hospitalization. Nausea, vomiting, mucositis, and diarrhea are the main digestive toxicities of chemotherapy. This review emphasizes the recent therapeutic approaches which could lead to a decrease of the incidence or the severity of these toxicities. Although marked progress has been accomplished these last years, a substantial degree of further improvement is needed to improve the effectiveness of specific treatments. Furthermore, research might focus on new strategies which may prevent the development of overall toxicity, by increasing the selectivity of chemotherapy on tumor cells.

Antineoplastic Agents↗
PubMed2001

[Oxaliplatin in combination with non fluoropyrimidine drugs in colorectal cancer].

After decades of exclusive use of fluorouracil in the treatment of metastatic colorectal cancer, three new drugs, among them oxaliplatin, have recently shown interesting results. Oxaliplatin has an activity when it is given alone but this drug is particularly interesting for combination chemotherapy because it has a favourable toxicity profile without important haematologic or digestive toxicities and because it has a convenient schedule of administration (short infusion every two or three weeks). Phases I and II studies have demonstrated the feasibility of the combination of raltitrexed and oxaliplatin. A recent phase II study has evaluated the efficacy of this new combination in 71 non pre-treated patients. The observed response rate was high: 59.5%. The combination of oxaliplatin and irinotecan has been assessed in three phase I studies (two with a three-weekly schedule and the last one with a biweekly schedule). These studies have determined the doses which could be used in further phase II studies, these doses were close to the doses used in monotherapy. Results of the efficacy of the three-weekly schedule are available only in second line therapy, with 42% of objective response rate in 36 patients. The dose intensity was maintained with the use of hematopoietic growth factors. These new combinations with oxaliplatin give us the opportunity to treat the patient with schedules excluding fluorouracil which has a variable metabolism.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Radiation-induced stricture of the papilla and the common bile duct: successful treatment with balloon dilation].

Radiation-induced lesions of the bile ducts rarely occur and may be difficult to manage. We report the case of a 59-year old woman who developed radiation-induced stenosis of the papilla and the common bile duct 25 years after abdominal radiation therapy for abdominal non-Hodgkin's lymphoma. She presented with recurrent cholangitis and chronic cholestasis. Endoscopic results showed dilation of the intrahepatic bile ducts, radiation-induced inflammation and narrowing of the antrum and the duodenum, and stricture of the papilla and the last few millimeters of the common bile duct. The patient was treated with endoscopic balloon dilation. Forty-two months after endoscopic dilation, the patient remained asymptomatic with normal liver tests and no biliary dilation at ultrasound.

Bile Duct Diseases↗
PubMed2000

Phase I and pharmacokinetic study of the camptothecin analog DX-8951f administered as a 30-minute infusion every 3 weeks in patients with advanced cancer.

PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg/m(2). All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L/h.m(2). The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg/m(2). CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg/m(2) every 3 weeks in patients previously treated with chemotherapy.

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

Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance.

BACKGROUND: The somatostatin analogues lanreotide and octreotide have previously been shown to be effective in controlling flushing and diarrhea in patients with carcinoid syndrome. As lanreotide requires injection only every 10 days, compared with twice-daily injections of octreotide, a direct comparison between these two treatments in terms of patient acceptability, patient preference, and efficacy in controlling symptoms was performed in patients with carcinoid syndrome. METHODS: Thirty-three patients with carcinoid syndrome were included in an open, multicenter, crossover study. Half of the patients received octreotide 200 microg subcutaneously twice or thrice daily for 1 month followed by lanreotide 30 mg intramuscularly every 10 days for 1 month, while the other half commenced with lanreotide followed by octreotide in a similar fashion. Quality-of-life assessments were performed at each visit and patient preference for one of the two treatments evaluated. The number and intensity of flushing episodes and bowel movements, urinary 5-hydroxyindoleacetic acid (5HIAA) levels, and plasma serotonin levels were recorded. RESULTS: No significant differences were found between lanreotide and octreotide in terms of quality of life. The majority of patients (68%) preferred lanreotide (P = 0.03), largely due to its simplified mode of administration. Disappearance or improvement in flushes occurred in 53.8% of patients (14 of 26) while on lanreotide and in 68% (17 of 25) on octreotide. A disappearance or improvement of diarrhea in 45.4% (10 of 22) on lanreotide, compared with 50% (11 of 22) on octreotide, was also observed. Lanreotide and octreotide were equally effective in reducing urinary 5HIAA levels and plasma serotonin levels. Both treatments were well tolerated, with mild symptoms of abdominal pain and nausea observed in 29% and 14% receiving octreotide and lanreotide, respectively. CONCLUSIONS: Lanreotide and octreotide are equally efficacious in terms of symptom control and reduction in tumor cell markers for patients with carcinoid syndrome. Due to its simplified mode of administration, most patients prefer treatment with lanreotide.

Antineoplastic Agents↗
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

Factors predicting for efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU)+/-folinic acid (FA) in a compassionate-use cohort of 370 5-FU-resistant advanced colorectal cancer (CRC) patients.

Univariate and multivariate analyses were performed on data from 370 5-fluorouracil (5-FU)-resistant advanced colorectal cancer patients treated with oxaliplatin (Eloxatin)/5-FU+/-folinic acid (FA) to identify prognostic factors for oxaliplatin-based treatment. The response rate was 14.6% (95% confidence interval (CI): 11.0-18.2%), median time to progression was 4.3 months (95% CI: 3.9-4.7), and median overall survival 9.7 months (95% CI: 8.5-10.8). Multivariate analysis indicated < 2 prior chemotherapy regimens, bi-weekly treatment administration schedule (versus tri-weekly) and continuous chronomodulated delivery (CCM) as significantly associated (P < 0.05) with a higher overall response rate. Performance status (PS) < 2, having only one involved organ, biweekly schedule and CCM were associated (P < 0.05) with a longer time to progression. Good PS, one involved organ, low alkaline phosphatase (AP) serum levels, bi-weekly schedule and CCM were significantly correlated with longer overall survival, while confirming the efficacy of oxaliplatin/5-FU+/-FA in this indication.

Adult↗
PubMed2000

A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies.

PURPOSE: Gemcitabine and vinorelbine are active drugs with broad spectrum of activity and manageable toxicity in clinical trials. The aims of this study were to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of gemcitabine and vinorelbine to be recommended for phase II studies in patients with advanced cancers. PATIENTS AND METHODS: Drugs were given as 30-min infusions on day 1 and 8 (vinorelbine before gemcitabine) every 3 weeks. Thirty-six patients (male:female ratio 25:11; mean age 54, PS > 60) were treated including 1 retroperitoneal sarcoma, 7 head and neck, 10 lung, 4 thyroid, 6 pancreatic, 1 bladder, 2 ovary, 2 gastric, 1 rectum, 1 unknown primary, and 1 renal cell carcinoma. Doses of gemcitabine/vinorelbine ranged from 800/20 mg/m2 to 1500/30 mg/m2. RESULTS: The dose-limiting toxicity was neutropenia. A transient grade 2-3 elevation of transaminases was frequently observed at several dose-levels, although this toxicity did not appear to be dose dependant and was reversible at day 21 before the next cycle. Other toxicities were mild and easily manageable, consisting of fatigue and flu-like syndromes. Since the MTD was not reach at the higher dose-level, the recommended dose level of the gemcitabine-vinorelbine combination was 1500/30 mg/m2. One toxic death due to hematologic toxicity was reported in a heavily pretreated patient who underwent prior chemotherapy and pelvic radiotherapy. A total of 12 patients were treated at the recommended dose level which was associated with grade 3-4 neutropenia in 3 of 12 patients and in 22.9% of cycles. CONCLUSIONS: This study estimates that the recommended dose for phase II studies of gemcitabine-vinorelbine is 1500/30 mg/m2 at day 1 and 8 every three weeks. A careful monitoring of the hematologic toxicity is recommended in heavily pretreated patients and in patients who received pelvic radiotherapy. Partial responses observed in a patient with an advanced cisplatin-5-fluorouracil-resistant pancreatic adenocarcinoma and in a patient with mesothelioma support further evaluation of this combination in patients with tumors refractory to classical antitumor agents.

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

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↗
PubMed2000

Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year.

OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of radiofrequency ablation of hepatic metastases performed either percutaneously for treatment of hepatic metastases in patients deemed ineligible for surgery or intraoperatively during partial hepatectomy to destroy unresectable metastases. SUBJECTS AND METHODS: Sixty-eight patients with 121 hepatic metastases (<5 metastases per patient) that were mainly colorectal in origin underwent 76 sessions of radiofrequency ablation with cooled-needle electrodes under sonographic guidance. Twenty-one patients with 33 metastases of 5-20 mm in diameter (mean +/- SD,13 +/- 7 mm) underwent intraoperative radiofrequency ablation. Forty-seven patients with 88 metastases of 10 to 42 mm in diameter (mean +/- SD, 26 +/- 9 mm) were treated with percutaneous radiofrequency ablation. Procedure efficacy was evaluated with dynamic enhanced CT and MR imaging performed 2, 4, and 6 months after treatment and then every 3 months. RESULTS: Radiofrequency ablation allowed eradication of 91% of the 100 treated metastases that were followed up for 4-23 months (mean, 13.7 months). Tumor control was equivalent for percutaneous radiofrequency ablation (90%) and for intraoperative radiofrequency ablation (94%). Failure to achieve tumor control occurred mostly with the largest tumor nodules. One bilioperitoneum and two abscesses were the major complications encountered after treatment of 121 metastases with a follow-up of more than 2 months. CONCLUSION: Radiofrequency ablation appears to be a promising therapeutic modality capable of extending the possibilities of partial hepatectomy and of efficiently treating small metastases percutaneously.

Adult↗
PubMed2000

[Complications and tolerance of heated intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis: results of a phase I-II study of peritoneal carcinomatosis from different sources].

Peritoneal carcinomatosis represents the terminal stage of adenocarcinomas of the gastrointestinal tract. A new treatment combining cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia has been used with encouraging results. The purpose of this study was to report the complications associated with this treatment. Fourty procedures were carry out in 37 patients. Death occurred in 3 patients. Major medical complications were 13 pulmonary infections, 11 acute renal failure (with only 3 who needed dialysis) and 10 patients with neutropenia grade 3 and 4 toxicity. Intra-abdominal complications occurred in 16 patients (there were 11 anastomotic leak and/or bowel perforation, and 12 intra-abdominal infections). Some complications like secretory diarrhea or tubulopathia which were related to these treatment need further investigations. Six procedures were without any complications, 6 presented minor ones and 22 major complications. Adverse effects were relatively important with this new treatment strategy. This was maybe due to a learning process; there is no death and only one anastomotic leak in our last study including 30 patients with cytoreductive surgery and intraperitoneal chemotherapy-hyperthermia.

Adolescent↗
PubMed2000

[Response of metastatic colorectal cancers to treatment with CPT11 (irinotecan): implications of the mismatched base repair system].

AIMS: The aim of our study was to assess the potential relationships between tumor responsiveness to CPT11, an analogue of camptothecin, which selectively inhibits DNA topoisomerase I, and the microsatellite instability, a feature of tumors with DNA mismatch repair defect. METHODS: We designed a retrospective clinical study including 35 patients with metastatic colorectal cancer treated with CPT11, for which we analyzed the expression of hMLH1 and hMSH2 in the tumor and determined microsatellite status of repeated mononucleotide tracts present in the coding region of RII-TGFB, BAX, hMSH3 and hMSH6 genes. RESULTS: A partial or minor response was observed in 9 patients, disease stabilization in 14 patients and progression in 12 patients. Staining of hMLH1 was undetectable in 2 of the 35 tumors, while only 1 tumor lacked hMSH2 expression. Four of the 31 tumors analyzed displayed intragenic microsatellite instability. We found a good correlation between inactivation of TGFB-RII, BAX or hMSH3 genes and tumor response to CPT-11 (P =0.002). CONCLUSION: Our preliminary data suggest that intragenic microsatellite instability may influence tumor response to CPT-11 in patients with colorectal cancer.

Adaptor Proteins, Signal Transducing↗