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M Clavel

Publications and source records attributed to M Clavel.

At least 19 recordsLinked to original sources
PubMed2001

Intensification of adjuvant chemotherapy: 5-year results of a randomized trial comparing conventional doxorubicin and cyclophosphamide with high-dose mitoxantrone and cyclophosphamide with filgrastim in operable breast cancer with 10 or more involved axillary nodes.

PURPOSE: To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes. PATIENTS AND METHODS: Patients (n = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m(2) plus cyclophosphamide 600 mg/m(2), with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates. RESULTS: There were no significant differences in DFS (P =.44), DDFS (P =.67), or OS (P =.99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P =.01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P <.001). CONCLUSION: This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m(2) with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide.

Adult↗
PubMed2001

[Pseudoneoplastic forms of bronchiolitis obliterans with organizing pneumopathy (BOOP)].

Chronic obstructive bronchiolitis with organizing lung disease is an anatomoradioclinical entity characterized by nonspecific inflammation associated with recurrent migratory minimally dense alveolar opacities on the chest x-ray poorly responsive to corticosteroid therapy. Excepting this typical presentation, other clinical forms may occur. We report the cases of two patients with an exceptional localized presentation raising the differential diagnosis of lung cancer.

Aged↗
PubMed2000

Multivariable analysis of prognostic factors for toxicity and survival for patients enrolled in phase I clinical trials.

BACKGROUND: Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials. PATIENTS AND METHODS: One hundred fifty-four patients treated on a phase I clinical trial in our institute were evaluated retrospectively. Univariable and multivariable analyses of patients' characteristics were undertaken to determine their effects on the probability of grade 3 and 4 toxicity and on survival. RESULTS: Grade 3 or 4 toxicity was experienced by 56 patients (36%): dosage level at entry (P < 0.001) and age over 65 years (P = 0.03) were independently associated with the risk of toxicity. Median overall survival was 5 months. The multivariable analysis identified performance status 2 or 3 (P < 0.001) and lactate dehydrogenase levels greater than 600 UI (P < 0.001) as independent adverse prognostic variables for overall survival. Using these two parameters, we determined a prognostic index which allowed us to discriminate three risk groups of patients with an observed median survival of 8.5, 4.5 and 1.5 months, respectively. CONCLUSIONS: Subgroups with different survival expectancy can be identified among patients who are eligible for phase I clinical trials. If confirmed, the proposed prognostic model may be useful for therapeutic decision making in palliative oncology.

Adult↗
PubMed1999

[Pneumothorax].

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Diagnosis, Differential↗
PubMed1999

[Symptomatic renal metastases of bronchial carcinoma].

Renal metastasis from carcinoma of the lung is rarely a clinical problem. Autopsic series however prove that the kidney is a frequent metastatic organ (20%). We report the case of a 43-years-old male patient affected with a squamous cell carcinoma of the lung, with bilateral renal extension. These secondary localizations were detected through a left flank pain prior to a systemic inflammatory response syndrome. The absence of hematuria (even microscopic) contrasted with the importance of the lesions. The age, along with the poor general state of our patient and the absence of any CT specificity justified an exploratory lobotomy. The pathologic analysis of the renal biopsies confirmed the metastatic nature of the lesion.

Adult↗
PubMed1998

Malignant melanotic schwannoma fine-needle aspiration biopsy findings.

We describe the cytologic, histologic, and clinical features of two cases of melanotic schwannoma, arising in the neck and superior mediastinum, respectively. Cytologic findings in both cases included the presence of cells with heavily pigmented cytoplasm, showing long branching projections. The cells were arranged in clusters, with ill-defined boundaries. Histologic findings included interlacing fascicles of cells, with abundant melanin pigment, calcification, and necrosis. Immunohistochemical stains were positive for S. 100 protein and anti-human melanoma (HMB45). Both patients died with metastases.

Adult↗
PubMed1998

Phase I clinical and pharmacokinetic study of S9788, a new multidrug-resistance reversal agent given alone and in combination with doxorubicin to patients with advanced solid tumors.

PURPOSE: The objectives of this phase I study were to evaluate the toxic effects and the maximum tolerated dose (MTD) of S9788, a new modifier of multidrug resistance (MDR), when given alone and in combination with doxorubicin to patients with advanced solid tumors; to achieve a potentially active plasma concentration of S9788; and to study the pharmacokinetics of both drugs. METHODS: A total of 26 patients (median age 58 years) entered the study. S9788 was given alone as a 30-min infusion at day 1 and in combination with a 50-mg/m2 bolus of doxorubicin at days 8 and 29. Dose levels of S9788 were escalated from 8 to 96 mg/m2 according to the modified Fibonacci scheme. Plasma samples were taken predose as well as during and up to 48 h after the beginning of infusion for S9788 and doxorubicin quantitation. Fractionated urine samples were also collected for up to 24 h for S9788 determination. RESULTS: The dose-limiting side effects of S9788 consisted of bradycardia, sometimes associated with faintness or dizziness. The MTD of S9788 was 96 mg/m2. No enhancement of doxorubicin toxicity was observed. One partial response (duration 140 days) was observed at 96 mg/m2 in a patient with multiple lung metastases from a refractory urothelial carcinoma. Pharmacokinetic studies were performed in 24 patients. Since the mean apparent elimination half-life of S9788 was 46 +/- 23 h and the last plasma sampling time was 48 h, only model-independent parameters were considered. Plasma levels of S9788 were below the limit of quantitation (4 x 10[-3] microM) before each drug administration. S9788 plasma levels of up to 3.7 microM could be obtained with this administration schedule. The urinary elimination of the unchanged drug was negligible, whatever the collection period. In spite of the large inter- and intraindividual variability, plasma pharmacokinetics of S9788 given as a 30-min i.v. infusion were linear up to 96 mg/m2 and were not modified by doxorubicin administration. Doxorubicin pharmacokinetic parameters did not seem to be influenced by S9788 coadministration. CONCLUSION: The dose-limiting toxicity of S9788 consisted of bradycardia or clinical symptoms suggesting a vasovagal impact such as faintness or dizziness. The MTD of S9788 was 96 mg/m2. The pharmacokinetic parameters of doxorubicin in this study were close to those usually described and were not influenced by escalation of the S9788 dose. No pharmacokinetic interaction was observed between S9788 and doxorubicin. The clinical tolerability of the combined treatment is in good agreement with the pharmacokinetic findings, since no enhancement of doxorubicin toxicity was observed.

Adult↗
PubMed1998

[Pancytopenia and pulmonary tuberculosis. Significance of a hemophagocytic syndrome].

Haemophagocytic syndromes or syndromes involving macrophage activation are rare complications of tuberculosis, whether they be pulmonary or polyvisceral. They are characterised by an anomalous increase in the phagocytic power of macrophages with phagocytosis of the formed elements of blood. The clinical biological picture associates a change in the general physical state accompanied by organomegaly, hyperferritinaemia and pancytopenia. Their occurrence is a poor prognostic factor and few treatment seem to check this mechanism. The authors report a rare case of marked macrophage activation syndrome complicating pulmonary tuberculosis in a patient who was HIV negative without an underlying blood disturbance and a favourable outcome.

Aged↗
PubMed1997

[Continuous intrathecal injection of baclofen in generalized tetanus. A therapeutic alternative].

BACKGROUND: In France, tetanus is diagnosed predominantly in the elderly due to the absence of vaccination in this population. Mortality remains high and is mainly related to complications secondary to prolonged hospitalization, intravenous administration of benzodiazepines, and at times curares. Baclofen, a selective agonist of GABAB receptors, directly counteracts the effects of the tetanic toxin. CASE REPORT: We report the case of a 92-year-old man suffering from tetanus, who fully recovered after a myorelaxant treatment based solely on intrathecal baclofen administration. Continuous intrathecal administration of baclofen resulted in a marked muscular relaxation with minor side effects (bradycardia, sleepiness), which rapidly stopped after the cessation of the treatment. Initial careful titration is required in order to determine the optimal dose of baclofen which provides a substantial myorelaxation together with minor central effects. Low concentration of baclofen may facilitate its diffusion. DISCUSSION: Continuous intrathecal administration of barclofen appears to be a valuable alternative therapy in tetanus. This new therapeutic modality promises to improve the prognosis of this condition, especially in the elderly.

Aged↗
PubMed1997

[Pulmonary infection caused by Fusobacterium nucleatum].

Thoracic infection by anaerobes are uncommon diseases and often presents difficulty in diagnosis. We report a case of thoracic infection due to Fusobacterium Nucleatum. A 60-year old man presented a lesion infiltrating from the lung to the thoracic wall. Fusobacterium Nucleatum was isolated on pus collected. Treatment by penicillin, metronidazole combined with surgical drainage was highly effective.

Anti-Bacterial Agents↗
PubMed1996

Breast cancer prognostic significance of some modified urinary nucleosides.

The prognostic significance of six urinary modified nucleosides, 5-methylcytidine (5-MeCyd), 4-acetylcytidine (4-AcCyd), 1-methylinosine (1-MeIno), 1-methyladenosine (1-MeAdo), 7-methylguanosine (7-MeGua) and pseudouridine (psi-Urd) was evaluated in 68 breast cancer patients of the specialized cancer hospital of Lyon (France). Excretions of 1-MeIno and 1-MeAdo were significantly higher in patients hospitalized in the medical rather than surgical ward, reflecting more advanced disease, and also among patients who died within 5 years of follow-up as compared to those still alive. These results suggest an unfavourable prognostic significance of high urinary excretion of 1-MeIno and 1-MeAdo in breast cancer patients.

Biomarkers, Tumor↗
PubMed1996

Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies.

BACKGROUND: CPT-11 (irinotecan), a camptothecin-derived anticancer agent with DNA topoisomerase 1 inhibitory activity, has demonstrated a broad spectrum of in vitro and in vivo activity in solid tumour models including multidrug-resistant tumours. This review details the rationale for the dosage schedule of CPT-11 selected for phase II studies, based on the results of 3 European phase I dose-escalating trials in patients with solid tumours. PATIENTS AND METHODS: CPT-11 was administered as a 30-minute intravenous infusion once every 3 weeks (schedule 1), once daily for 3 consecutive days every 3 weeks (schedule 2) or once weekly every 3 out of 4 weeks (schedule 3). RESULTS: Neutropenia and diarrhoea were the major dose-limiting toxicities in all of the studies. The maximum tolerated dose of CPT-11 was 115 and 145 mg/m2/day for schedules 2 and 3, respectively. With schedule 1, diarrhoea became dose-limiting at 350 mg/m2 but was manageable with high-dose loperamide therapy. CONCLUSIONS: CPT-11 350 mg/m2 administered as an intravenous infusion once every 3 weeks was chosen for further evaluation in early phase II studies, since this dosage regimen allowed the highest dose intensity with the least toxicity and was convenient for outpatient use. The place of higher doses (with intensive antidiarrhoeal support) and other administration schedules (e.g., protracted infusion) warrant further investigation.

Adolescent↗
PubMed1996

Phase I and pharmacology study of intoplicine (RP 60475; NSC 645008), novel topoisomerase I and II inhibitor, in cancer patients.

Intoplicine (RP 60475F; NSC 645008) is a novel 7H-benzo[e]pyrido[4,3-b]indole derivative which interacts with both topoisomerases I and II. Because of its high activity in preclinical cancer models, original mechanism of action and acceptable toxicity profile, intoplicine was further evaluated in a phase I and pharmacology study. Thirty-three (33) patients (24 men and nine women) meeting standard phase I eligibility criteria were included: median age was 56 years, performance status 0-1 in 28 patients and 2 in five patients. Tumor primary sites were head and neck (9), colon (6), lung (3) and various other sites (15). Thirty-one patients had received prior radiotherapy and/or chemotherapy. Sixty-nine coursed of intoplicine were administered as a 1 h i.v. infusion at dose levels ranging from 12 to 360 mg/m2. Dose-dependent and reproducible hepatotoxicity was dose limiting in three out of four patients at 360 mg/m2: this toxicity was reversible in two of three patients, but fatal in one. Two sudden deaths occurred in this study at 12 and 48 mg/m2, and the drug implication could not be excluded. No myelosuppression was noted. Hepatotoxicity is therefore dose limiting at 360 mg/m2, and the phase II recommended dose is 270 mg/m2 every 3 weeks with close monitoring of hepatic and cardiac functions. Intoplicine pharmacokinetics was determined in plasma (23 patients) and whole blood (18 patients) at doses ranging from 12 to 360 mg/m2. Intoplicine plasma concentration decay was either bi- or triphasic with the following pharmacokinetic values (mean +/- SEM): half-life alpha, 0.04 +/- 0.004 h; half-life beta, 0.61 +/- 0.13 h; terminal half-life, 19.4 +/- 4.0 h; mean residence-time (MRT), 11.3 +/- 2.4; total plasma clearance (CL), 74 +/- 5 l/h; volume of distribution beta (V beta), 1982 +/- 477 l: volume of distribution at steady state (Vss): 802 +/- 188 l. both the area under the plasma concentration versus time curves (AUC) and the maximum plasma concentrations (Cmax) increased linearly with the intoplicine dose, indicating linear pharmacokinetics (AUC: r = 0.937; slope = 0.01305; p < 0.001; Cmax: r = 0.847; slop = 0.01115; p < 0.001). Plasma AUC was also predicted very accurately by the Cmax values (r = 0.909; slope = 1.0701; p < 0.001). Other plasma pharmacokinetic parameter values increased significantly with dose, e.g. the terminal half-life (r = 0.748, p < 0.001) the MRT (r = 0.728, p < 0.001), the V beta (r = 0.809, p < 0.001), and the Vss (r = 0.804, p < 0.001). This was probably due to a longer detectability of the drug in plasma at higher doses. Blood pharmacokinetics was also evaluated in 18 patients since it was found that red blood cells represented a significant drug reservoir for intoplicine. Blood intoplicine disposition curves were either bi- or triphasic with the following pharmacokinetic parameter values (mean +/- SEM): half-life alpha, 0.04 +/- 0.01 h; half-life beta, 0.94 +/- 0.22 h; terminal half-life, 57.1 +/- 6.6 h; MRT, 82.2 +/- 9.9 h; CL, 18 +/- 3 l/h; V beta, 1188 +/- 147 I; Vss 1163 +/- 138 I. Blood pharmacokinetics was linear, since AUC and Cmax increased linearly with dose (AUC: r = 0.879; slop = 0.06884; p < 0.001; Cmax: r = 0.835, slop = 0.01223; p < 0.001). Blood AUC values could also be determined by the blood Cmax (r = 0.768; slop = 5.0206; p < 0.001). Other blood pharmacokinetic parameter values presented a dose dependence, e.g. the terminal half-life (r = 0.626, p = 0.005), the V beta (r = 0.682, p = 0.002) and the Vss (r = 0.555, p = 0.017). The plasma or blood intoplicine concentrations achieved in vivo in humans are potentially cytotoxic levels based on preclinical in vivo and in vitro data. In conclusion, the phase II recommended dose of intoplicine is 270 mg/m2 administered as a 1 h i.v. infusion every 3 weeks. Plasma and blood pharmacokinetics were linear within the dose range studied. Potentially cytotoxic concentrations were reached at clinically achievable doses.

Adult↗
PubMed1996

Occipital neuralgia secondary to exuberant callus formation. Case report.

The authors report the case of a 78-year-old woman suffering from right occipital neuralgia in whom computerized tomography and magnetic resonance images demonstrated an irregular bone mass in the C-2 vertebral body. This "bone tumor" happened to be an exuberant callus formation that arose as a result of a previous axis body fracture. The patient's occipital pain was immediately relieved after she underwent C2-3 root release.

Aged↗
PubMed1995

Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation.

Docetaxel, a novel anticancer agent, was given to 26 patients by short i.v. infusion (1-2 h) at various dose levels (70-115 mg/m2, the maximum tolerated dose) during 2 phase I studies. Two population analyses, one using NONMEM (nonlinear mixed-effect modeling) and the other using NPML (nonparametric maximum-likelihood), were performed sequentially to determine the structural model; estimate the mean population parameters, including clearance (Cl) and interindividual variability; and find influences of demographic covariates on them. Nine covariates were included in the analyses: age, height, weight, body surface area, sex, performance status, presence of liver metastasis, dose level, and type of formulation. A three-compartment model gave the best fit to the data, and the final NONMEM regression model for Cl was Cl = BSA(Theta1 + Theta02 x AGE), expressing Cl (in liters per hour) directly as a function of body surface area. Only these two covariates were considered in the NPML analysis to confirm the results found by NONMEM. Using NONMEM [for a patient with mean AGE (52.3 years) and mean BSA (1.68 m2)] and NPML, docetaxel Cl was estimated to be 35.6 l/h (21.2 lh-1 m-2) and 37.2 l/h with interpatient coefficients of variations (CVs) of 17.4% and 24.8%, respectively. The intraindividual CV was estimated at 23.8% by NONMEM; the corresponding variability was fixed in NPML in an additive Gaussian variance error model with a 20% CV. Discrepancies were found in the mean volume at steady state (Vss; 83.21 for NPML versus 1241 for NONMEM) and in terminal half-lives, notably the mean t1/2 gamma, which was shorter as determined by NPML (7.89 versus 12.2 h), although the interindividual CV was 89.1% and 62.7% for Vss and t1/2 gamma, respectively. However, the NPML-estimated probability density function (pdf) of t1/2 gamma was bimodal (5 and 11.4 h), probably due to the imbalance of the data. Both analyses suggest a similar magnitude of mean Cl decrease with small BSA and advanced age.

Adult↗
PubMed1995

Phase I study of RP 49532A, a new protein-synthesis inhibitor, in patients with advanced refractory solid tumors.

Giroline (RP 49532A) is a new protein-synthesis inhibitor with broad antitumor activity in experimental models. In the present phase I study, Giroline was given by 24-h i.v. infusion every 3 weeks at doses ranging from 3 to 15 mg/m2 to 12 patients with advanced refractory solid tumors. The dose-limiting toxic effects were delayed hypotension and severe asthenia. The maximum tolerated dose (MTD) was 15 mg/m2. Transient nausea and vomiting during infusion were reported at all dose levels. Mild reversible prolongation of prothrombin time and activated partial thromboplastin time was observed in most patients at dose levels above 3 mg/m2. No antitumor activity was observed. The toxicity profile of Giroline precludes further evaluation in cancer patients.

Adult↗