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Biomedical subjects

J Taïeb

Publications and source records attributed to J Taïeb.

At least 19 recordsLinked to original sources
PubMed2006

FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study.

BACKGROUND: The purpose of the study was to prospectively evaluate the efficacy and tolerability of the FOLFIRI.3 regimen in patients with unresectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven advanced pancreatic adenocarcinoma were treated with the FOLFIRI.3 regimen, consisting of irinotecan 90 mg/m(2) as a 60-min infusion on day 1, leucovorin 400 mg/m(2) as a 2-h infusion on day 1, followed by 5-fluorouracil (5-FU) 2000 mg/m(2) as a 46-h infusion and irinotecan 90 mg/m(2), repeated on day 3, at the end of the 5-FU infusion, every 2 weeks. RESULTS: Forty patients were enrolled, of whom 29 (73%) had metastatic disease. A total of 441 cycles were delivered (1-53). Grade 3-4 neutropenia occurred in 35% of the patients, accompanied by fever in two cases. Other relevant grade 3-4 toxic effects were nausea-vomiting (27%) and diarrhea (25%). Grade 2 alopecia occurred in 48% of the patients. There were no treatment-related deaths. The confirmed response rate was 37.5%. Stable disease was observed in 27.5% of the patients. The median progression-free and overall survivals were 5.6 months and 12.1 months, respectively. The 1-year survival rate was 51%. CONCLUSION: The FOLFIRI.3 regimen seems to be active on advanced pancreatic cancer and to have a manageable toxicity profile. The lack of cross-resistance between FOLFIRI.3 and gemcitabine-based regimens allows efficient second-line therapies.

Adult↗
PubMed2005

Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial.

PURPOSE: Gemcitabine (Gem) is the standard treatment for advanced pancreatic cancer. Given the promising phase II results obtained with the Gem-oxaliplatin (GemOx) combination, we conducted a phase III study comparing GemOx with Gem alone in advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were stratified according to center, performance status, and type of disease (locally advanced v metastatic) and randomly assigned to either GemOx (gemcitabine 1 g/m2 as a 100-minute infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour infusion on day 2 every 2 weeks) or Gem (gemcitabine 1 g/m2 as a weekly 30-minute infusion). RESULTS: Three hundred twenty-six patients were enrolled; 313 were eligible, and 157 and 156 were allocated to the GemOx and Gem arms, respectively. GemOx was superior to Gem in terms of response rate (26.8% v 17.3%, respectively; P = .04), progression-free survival (5.8 v 3.7 months, respectively; P = .04), and clinical benefit (38.2% v 26.9%, respectively; P = .03). Median overall survival (OS) for GemOx and Gem was 9.0 and 7.1 months, respectively (P = .13). GemOx was well tolerated overall, although a higher incidence of National Cancer Institute Common Toxicity Criteria grade 3 and 4 toxicity per patient was observed for platelets (14.0% for GemOx v 3.2% for Gem), vomiting (8.9% for GemOx v 3.2% for Gem), and neurosensory symptoms (19.1% for GemOx v 0% for Gem). CONCLUSION: These results confirm the efficacy and safety of GemOx, but this study failed to demonstrate a statistically significant advantage in terms of OS compared with Gem. Because GemOx is the first combined treatment to be superior to Gem alone in terms of clinical benefit, this promising regimen deserves further development.

Adenocarcinoma↗
PubMed2004

Combination of folinic acid, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in patients with advanced gastric or gastroesophageal junction carcinoma.

BACKGROUND: Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination. PATIENTS AND METHODS: Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m(2) on day 2 plus folinic acid 200 mg/m(2)/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m(2)/day on days 1 and 2, plus continuous 5-FU 600 mg/m(2)/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m(2) day 1 + bolus 5-FU 400 mg/m(2) day 1 + continuous 5-FU 2400 mg/m(2) on days 1 and 2 with cisplatin 50 mg/m(2) on day 2). RESULTS: All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4-10.9) and the overall survival was 13.3 months (95% CI 10.1-16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities. CONCLUSIONS: LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.

Adult↗
PubMed2003

Experimental indications for the response of the spectators to the participant blast.

Precise momentum distributions of identified projectile fragments, formed in the reactions 238U+Pb and 238U+Ti at 1A GeV, are measured with a high-resolution magnetic spectrometer. With increasing mass loss, the velocities first decrease as expected from previously established systematics, then level off, and finally increase again. Light fragments are on the average even faster than the projectiles. This finding is interpreted as the response of the spectators to the participant blast. The reacceleration of projectile spectators is sensitive to the nuclear mean field and provides a new tool for investigating the equation of state of nuclear matter.

Journal Article↗
PubMed2002

Phase I and pharmacokinetic study of E7070, a novel chloroindolyl sulfonamide cell-cycle inhibitor, administered as a one-hour infusion every three weeks in patients with advanced cancer.

PURPOSE: The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor. PATIENTS AND METHODS: E7070 was given as a 1-hour intravenous infusion every 3 weeks in two groups of patients with advanced solid tumors who met prespecified eligibility criteria (group A) or who met the same eligibility criteria but in addition were less heavily pretreated and had more favorable liver functions (group B). RESULTS: Forty patients (31 patients in group A and nine patients in group B) were entered. Dose escalation proceeded through eight levels (range, 50 to 1,000 mg/m(2)). In group A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring during the first cycle in two of seven patients treated at the doses of 700 mg/m(2) and two of four patients treated at 800 mg/m(2). Identical dose-limiting toxicities were observed in zero of six and two of three patients from group B at doses of 800 and 1,000 mg/m(2), respectively. Other toxicities included acne-like skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses greater than 400 mg/m(2), the area under the concentration-time curve increased disproportionately to the administered dose. Tumor stabilization lasting > or = 6 months was observed in six assessable patients. CONCLUSION: The recommended doses of E7070 in this schedule were 700 mg/m(2) (group A) and 800 mg/m(2) in patients who were less heavily pretreated (group B) with a moderate tumor burden. Prolonged disease stabilization observed in this study might warrant further investigation of E7070 in selected tumor types.

Adult↗
PubMed2002

[The new chemotherapy of colorectal cancers].

THE SITUATION: With around 35.000 new cases per year and a 40% mortality rate, colorectal cancer is a real problem of health care in France. Chemotherapy for metastatic disease has completely changed during the ten last years with the emergence of promising new drugs such as oxaliplatin and irinotecan. Oral 5-FU prodrugs have also shown an interesting efficacy in this setting. RESULTS: Showed increased response rate, progression free survival with both drugs, and overall survival, only with the irinotecan-based regimen. Moreover, after aggressive first-line chemotherapy, some patients can undergo surgical resection of the metastases, initially considered as unresectable. We still do not know if these aggressive first-line therapies should be proposed to all metastatic patients or only to a selected subgroup. The best strategies remain to be evaluated. IN THE SETTING OF ADJUVANT CHEMOTHERAPY: Of colorectal cancer, a 6-month 5-FU/folinic acid postoperative chemotherapy is actually the standard for the management of patients with positive lymph nodes (stage III). In stage II patients the benefit of such treatment remains controversial. The benefit of using oxaliplatin or irinotecan in association with 5-FU/folinic acid as adjuvant therapy is under investigation. CONCLUSION: In this 21st century, chemotherapy has a major place in the therapeutic management of colorectal cancer patients.

Antimetabolites, Antineoplastic↗
PubMed2002

Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer.

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.

Adenocarcinoma↗
PubMed2002

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma.

BACKGROUND: Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen. PATIENTS AND METHODS: Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored. RESULTS: Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths. CONCLUSIONS: This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

Adenocarcinoma↗
PubMed2000

Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids.

BACKGROUND/AIMS: Several observations point to an important role of interactions between polymorphonuclear neutrophils and cytokines in severe alcoholic hepatitis. The polymorphonuclear neutrophil activation status and the local and systemic pro- and anti-inflammatory cytokine responses were quantified. The effect of corticosteroids, widely used in this setting, was evaluated using these parameters. METHODS: We studied blood polymorphonuclear neutrophil functions in terms of L-selectin and beta2-integrin expression, H2O2 production and IL-8 and tumor necrosis factor alpha synthesis capacity. We also measured IL-8, tumor necrosis factor alpha and IL-10 plasma and liver tissue levels. Fifteen patients with alcoholic hepatitis were compared to 15 patients with alcoholic cirrhosis without alcoholic hepatitis, and to 10 healthy volunteers. The impact of a 28-day course of corticosteroids on blood neutrophils activation status and cytokine levels was evaluated in patients with alcoholic hepatitis. RESULTS: Blood polymorphonuclear neutrophils were activated, as shown by increased H2O2 production (48+/-6 vs 29+/-6 MFI in healthy controls), and decreased L-selectin expression (300+/-61 vs 449+/-59 in healthy controls). Upon stimulation, polymorphonuclear neutrophils synthesized large amounts of IL-8 (21.7+/-9.2 ng/ml vs 8.8+/-10 ng/ml in healthy controls) and tumor necrosis factor alpha (524+/-132 pg/ml vs 79+/-144 pg/ml in healthy controls). Tumor necrosis factor alpha and IL-8 plasma and tissue levels were markedly increased as IL-10 was barely detectable in alcoholic hepatitis patients, compared to cirrhotic patients and healthy controls. During steroid therapy, plasma levels of the pro-inflammatory cytokine IL-8 fell as early as day 14, while levels of the anti-inflammatory cytokine IL-10 increased on day 21. Finally, polymorphonuclear neutrophil functions returned to normal after treatment. CONCLUSION: Severe alcoholic hepatitis appears to be associated with polymorphonuclear neutrophil activation and an imbalance between pro- and anti-inflammatory cytokines; during steroid therapy a normalization of these parameters was observed.

Adrenal Cortex Hormones↗
PubMed1999

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation.

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.

Adult↗
PubMed1995

Scheduled administration of a gonadotrophin-releasing hormone antagonist (Cetrorelix) on day 8 of in-vitro fertilization cycles: a pilot study.

To assess in a pilot study the ability of a single injection of a GnRH antagonist (Cetrorelix) to prevent premature luteinizing hormone (LH) surges in an in-vitro fertilization (IVF) embryo transfer programme when administered on a fixed day in the late follicular phase, ovarian stimulation was carried out in 11 women with two ampoules of human menopausal gonadotrophin per day beginning on day 2 of the menstrual cycle. A 3 mg dose of Cetrorelix was administered on day 8 of the stimulation cycle. A second injection was administered 72 h later if ovulation was not triggered in the meantime. We did not observe a premature LH surge in any of the cycles studied. The injection of 3 mg Cetrorelix was capable of preventing LH surge in all the patients studied, introducing a very simple treatment protocol. Among the patients who received two injections (n = 3), the day of the first administration was delayed in two subjects due to slow follicular maturation kinetics. Out of 11 patients, 10 had an embryo transfer. Four clinical pregnancies were obtained (40% per embryo transfer), of which 3 are ongoing (30% per embryo transfer). A simple administration protocol for a new GnRH antagonist (Cetrorelix) was able to prevent LH surges in the 11 patients studied.

Adult↗