Biomedical subjects

Emmanuel Chamorey

Publications and source records attributed to Emmanuel Chamorey.

6 recordsLinked to original sources

PubMed2006

Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer.

BACKGROUND: Docetaxel is a well-recognized drug in patients with hormone-refractory prostate cancer (HRPC), either alone or combined with estramustine. In this indication, a Phase II trial was conducted investigating a docetaxel-capecitabine combination. METHODS: Forty-six patients presenting with documented HRPC were enrolled in the study. The treatment regimen consisted of docetaxel (D) at a dose of 35 mg /m2/week (intravenously, 3 consecutive weeks) plus oral capecitabine (C) at a dose of 625 mg/m2 twice daily (Days 5-18) every 28 days for 4 cycles. The primary endpoint was the biological response defined as a reduction in prostate-specific antigen (PSA) level > or =50%. Secondary endpoints were overall survival, safety, and quality of life. RESULTS: Thirty of 44 assessable patients (68.2%) achieved a biological response, 14 of whom (31.8%) normalized their PSA value. The median overall survival time was 17.7 months (95% confidence interval, 15.8 to not reached). Four treatment cycles were completed by 87% of the patients. Hematologic toxicity was mild. The main Grade 3-4 toxicities were cutaneous toxicity (13.1%) and changes in nails (6.5%). Physical functioning and role scales were higher before treatment (P = .02 and P = .003, respectively), fatigue and diarrhea were more frequent during and after treatment (P = .0003 and P = .03, respectively), and pain was lower during and after treatment. CONCLUSIONS: The results of the current study demonstrated the high efficacy of the DC combination in patients with HRPC, and the associated good tolerability. This combination offers a new alternative to the docetaxel-estramustine combination. Further randomized trials are warranted.

Adenocarcinoma↗

PubMed2006

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC).

BACKGROUND: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. METHODS: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3. RESULTS: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. CONCLUSION: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.

Adult↗

PubMed2004

Ceftriaxone monotherapy for the treatment of febrile neutropenia in patients with solid tumors: a prospective study of 100 episodes.

BACKGROUND: Broad-spectrum beta-lactam is the standard therapy for febrile neutropenia (FN) in cancer patients. The aim of our study was to evaluate the treatment of FN by a once-daily administration of ceftriaxone (CFX) alone. MATERIAL/METHODS: From Jan. 1, 1997 to Dec. 31, 2001 we prospectively analyzed 100 episodes of FN in 94 patients. Inclusion criteria were: fever > or = 38.5 degrees C, neutrophil count (NC) <500/microl, presumed short duration (<7 days), and no antimicrobial treatment within the preceding 72 h. Treatment consisted of 2 g daily intravenous CFX alone until NC>500. Success criteria were: afebrile within 48 hours under CFX alone and without secondary infection. RESULTS: Twenty-seven episodes occurred in patients with performance status (PS)>2. The median duration of neutropenia was 3.5 days (range 1-22). Etiology of fever was: 75 of unknown origin (FUO), 6 clinically defined (CDI), and 19 microbiologically documented (MDI). Median CFX treatment duration was 5 days. Successful response was obtained in 87% of cases; no deaths occurred. Treatment efficacy differed between FUO, CDI, and MDI with, respectively, 92.0, 83.3, and 68.4% success rates (p=0.042). Treatment failure was mostly observed in patients with PS > or = 2 (p=0.0001). Among the 13 failures, 4 resolved in less than 4 days with CFX alone and 9 required additional or modified antimicrobial treatment. CONCLUSIONS: Considering the marked practical advantages of CFX alone (well-tolerated treatment with minimum side effects, once-daily administration, low cost, and high response rates), this single-agent regimen appears to be a valuable option in treatment of FN in patients with solid tumors.

Adult↗

PubMed2004

Single ascending dose tolerability, pharmacokinetic-pharmacodynamic study of dihydropyrimidine dehydrogenase inhibitor Ro 09-4889.

PURPOSE: Ro 09-4889 was designed to enhance the anticancer efficacy of capecitabine (Xeloda) by generating a dihydropyrimidine dehydrogenase inhibitor (DPDi) 5-vinyluracil (5-VU) preferentially in tumor tissues. This study assessed the tolerance to Ro 09-4889 treatment, and related pharmacokinetic and pharmacodynamic data such as inhibition of DPD activity in peripheral blood mononuclear cells (PBMCs) and plasma uracil levels. EXPERIMENTAL DESIGN: This was a single-center, double-blind, placebo-controlled, single-dose escalation study in 64 healthy male volunteers at 1-, 5-, 20-, 50-, 75-, 100-, and 200-mg oral dose of Ro 09-4889. Also, food effect was assessed separately in a group dosed with 20 mg of the compound. RESULTS: No serious adverse effects or significant laboratory and electrocardiogram abnormalities were observed during the study. Ro 09-4889 has a short elimination half-life (t(1/2)) of 0.5 h, followed by metabolites 5'-deoxy-5-vinyluridine (5'-DVUR), 5'-deoxy-5-vinylcytidine (5'-DVCR), and 5-VU with t(1/2) of 1.3, 1.2, and 2 h, respectively. The major metabolite excreted in urine was 5-DVCR (45% of dose). The inhibition of PBMC DPD activity and the increase in plasma uracil were related to Ro 09-4889 dose. DPD inhibition versus dose and uracil AUC (area under the curve) versus dose were modeled using the E(max) model with a baseline effect. The model-predicted ED(50) value was 100 mg. CONCLUSION: Single oral doses of Ro 09-4889 ranging from 1 to 200 mg were well tolerated. On the basis of these findings, a 10-to-30-mg dose range of Ro 09-4889 combined with capecitabine could be appropriate for further evaluation in cancer patients.

Administration, Oral↗

PubMed2002

The raltitrexed-vinorelbine combination: a phase I pharmacokinetic and pharmacodynamic trial in advanced breast cancer.

PURPOSE: Combinations of vinorelbine (VRB) and drugs targeting thymidylate synthase (TS) such as 5-fluorouracil (5-FU) have proven clinical efficacy in the management of advanced breast cancer. Raltitrexed (RTX) is a recent TS inhibitor which shows advantages over 5-FU in terms of a lower incidence of toxicity along with a simpler administration schedule. We conducted a phase I trial of the VRB-RTX combination in 12 patients with advanced breast cancer. MATERIALS AND METHODS: Most of the patients were refractory to taxane-anthracycline combination therapy. Their median age was 51 years (range 33-70 years). RTX was given on day 1 and VRB on days 1 and 5 on a 3-week cycle. Three dose levels were initially planned with VRB and RTX increasing from 22.5 to 25 mg/m(2) and from 2.5 to 3 mg/m(2), respectively. RESULTS: From a total of 50 cycles (mean 4 cycles per patient, range 1-11), the maximal tolerated dose (MTD) was reached at VRB 25 mg/m(2) and RTX 3 mg/m(2) with grade 3-4 neutropenia as the dose-limiting toxicity (7/16 cycles and 3/5 patients at the MTD). Nine pretreated patients were evaluable for treatment efficacy and three of these showed an objective response (one complete response, two partial responses; mean duration 26 weeks, range 17-38 weeks). Pharmacokinetic follow-up was done for both drugs (RTX by LC-MS-MS and VRB by HPLC-UV detection). There was no interaction between RTX and VRB pharmacokinetics since the VRB AUC was not significantly modified between day 1 and day 5. There was no relationship between RTX AUC and hematological toxicity. In contrast, there was a highly significant relationship between the mean VRB AUC (days 1-5) and the absolute neutrophil count decrease (Emax model, Hill constant=4.38+/-2.59, EC(50)=508+/-53.2 micro g.h/l, r=0.75, P=0.0013). A similar relationship was noted for the platelet decrease but at the limit of statistical significance. CONCLUSIONS: The VRB-RTX combination appears to be a valuable treatment option in second-line treatment of advanced breast cancer. It is deliverable on an outpatient basis, shows an acceptable toxicity profile potentially manageable by VRB pharmacokinetic follow-up, and has promising antitumor activity in taxane-anthracycline-refractory patients. The recommended dose for further studies is VRB 22.5 mg/m(2) and RTX 3 mg/m(2).

Adult↗

PubMed2002

Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal cancer patients receiving fluorouracil-based chemotherapy: phenotypic and genotypic analyses.

PURPOSE: The aim of this multicenter prospective study was to evaluate the role of intratumoral parameters related to fluorouracil (FU) sensitivity in 103 metastatic colorectal cancer patients receiving FU-folinic acid. PATIENTS AND METHODS: Liver metastatic biopsy specimens were obtained for all patients and primary tumor biopsy specimens for 54 patients. Thymidylate synthase (TS), folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was determined by polymerase chain reaction; and p53 protein and mutations were analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis, respectively. RESULTS: p53 mutations were observed in 56.7% of metastases. TS activity was significantly higher in 2R/3R tumors as compared with 2R/2R or 3R/3R. TS activity in metastasis was the only parameter linked to clinical responsiveness (responders exhibited the lower TS, P =.047). Univariate Cox analyses demonstrated that TS activity in primary tumor (the greater the TS, the poorer the survival; P =.040), TS promoter polymorphism in primary tumor (risk of death of 2R/3R v 2R/2R, 2.68; P =.035), and p53 stop mutation in metastasis (risk of death of stop mutations v wild type, 3.14; P =.018) were the only significant biologic predictors of specific survival. Stepwise analysis did not discriminate between TS activity and TS polymorphism. CONCLUSION: Present results confirm the value of tumoral TS activity for predicting FU responsiveness, point out the importance of detailed p53 mutation analysis for predicting survival, and suggest that TS genotype in primary tumor carries a prognostic value similar to that of TS activity.

Adult↗