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C Chastang

Publications and source records attributed to C Chastang.

At least 91 records · Page 5Linked to original sources
PubMed1996

The group sequential triangular test for phase II cancer clinical trials.

In cancer, phase II clinical trials are usually noncomparative. Their purpose is to determine whether a new chemotherapy is effective enough to warrant further evaluation in phase III. Therefore, in order to meet ethical requirements, decision-making methods must allow for early termination when inefficacy (or efficacy) is clear. We previously extended the Triangular Test, a group sequential method initially proposed for phase III trials, to phase II trials and demonstrated its advantages (i.e., type I error rate alpha and power close to the nominal values, reduction of the sample size) over other methods. The aim of this paper is to present the Triangular Test from a practical standpoint that will facilitate its application to phase II clinical trials in oncology. After summarizing the minimal theoretical knowledge required to use the method appropriately, we discuss its use in the design and analysis of a phase II cancer trial.

Algorithms↗
PubMed1996

Dermatologic findings in HIV-1-infected patients: a prospective study with emphasis on CD4+ cell count.

BACKGROUND: Skin manifestations are common in patients infected with the human immunodeficiency virus (HIV) but the prognostic significance of may of them is not clear. METHODS: Skin disorders were studied in a cohort of 267 HIV-infected patients followed prospectively and were correlated to the CD4+ cell count. RESULTS: Among the most specific to HIV infection, Kaposi's sarcoma, oral hairy leukoplakia, molluscum contagiosum, xerosis and oral candidiasis were statistically associated to a low CD4+ cell count (200-300 CD4+/mm3; p < 0.001). Kaposi's sarcoma, oral candidiasis and molluscum contagiosum were more frequent in homosexual males (p < 0.05). Genital warts were more frequent in intravenous-drug users (p < 0.001). CONCLUSIONS: These results suggest that dermatological findings are useful clinical predictors of the presence or progression of HIV infection.

Adult↗
PubMed1996

Efficacy of 2-month total parenteral nutrition in AIDS patients: a controlled randomized prospective trial. The French Multicenter Total Parenteral Nutrition Cooperative Group Study.

OBJECTIVE: To evaluate the efficacy of total parenteral nutrition in AIDS patients. DESIGN: A prospective, randomized, controlled, multicentre trial. METHODS: Over a period of 2 months, 31 malnourished and severely immunodepressed AIDS patients were assigned to receive either dietary counselling (n = 15) or home total parenteral nutrition (TPN; n = 16) via a central venous access after an educational program. Results were analysed by intent-to-treat basis. RESULTS: Bodyweight change was +8 kg (+13 +/- 3%) in the TPN group and -3 kg (-6 +/- 2%) in the control group (P < 0.0006). Lean body mass increased in the TPN group (+9 +/- 3%) and decreased in the control group (-5 +/- 3%; P < 0.004) while body cell mass increased in the former (+15 +/- 4%) and decreased in the latter (-12 +/- 6%; P < 0.002). Nutritional subjective global assessment, subjective self-reported health feeling and Karnofsky index were also improved by TPN. Infection line sepsis incidence remained low (0.26 per 100 patient-days). However, no difference in survival rate was exhibited between the two groups by the log-rank test. CONCLUSION: We conclude that home TPN is an efficient treatment of malnutrition in severely immunodepressed AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Prognostic factors of prosthetic valve endocarditis. Apropos of 122 cases].

The prognostic factors of 122 patients suffering from prosthetic valve endocarditis between 1978 and 1992 were studied by univariate and multivariate analysis. The principal causative organisms were Staphylococcus aureus (33%), streptococci (20%), coagular-negative staphylococci (12%), enterococci (10%) and gram-negative bacilli (9%). The 4 month survival rate was 66% (42 deaths). The main predictive factor for death was infection with S. aureus (75% vs 15% with other organisms). In S. aureus infection, multivariate analysis identified the following predictive factors for death: a prothrombin ratio less than 30% (RR = 8.3), mediastinitis (RR = 4.9), cardiac failure (RR = 4.4) and septic shock (RR = 2.6). In cases of infection with other organisms, the following factors were predictive of death: a prothrombin ratio of less than 30% (RR = 32.26), renal failure (RR = 7.31) and cardiac failure (RR = 6.07). In patients with S. aureus infection, survival was better after than without surgery: 9/20 (45%) versus 0/20 (p < 0.001). In infection with other organisms, there was no difference in a survival after surgical (89%) or medical therapy (81%). Chronic endocarditis relapses over 1 to 5 years was observed in 9 cases. All patients were reoperated a total number of 18 times with 5 deaths. Very prolonged antibiotic therapy is recommended in these patients. The authors conclude that endocarditis not due to S. aureus and without complications may be treated medically. Rapid reoperation is necessary in all other cases.

Adult↗
PubMed1996

[Treatment of Guillain-Barré syndrome by plasma exchange: proposal of a therapeutic strategy].

Although the favorable effect of plasma exchange (PE) has been demonstrated in Guillain-Barré syndrome, the optimal number of PE and management at different degrees of gravity remain to be ascertained. A new controlled multicentric trial is therefore being conducted since 1986. Mid-term results show that 2 PE give better results than 0 in patients who are still able to walk. Inversely, 6 PE do not give better results when ventilatory assistance was initially required. It is therefore logical to propose 2PE as early as possible. Two supplementary PE can be used in case of disease progression. Use of high dose immunoglobulins is not justified except when PE is contraindicated.

Humans↗
PubMed1996

Assessment of joint space width in patients with osteoarthritis of the knee: a comparison of 4 measuring instruments.

OBJECTIVE: To evaluate the intra and interobserver reproducibility of 4 measuring instruments for assessing joint space width in knee osteoarthritis (OA) and to estimate the effects of patients, instrument, session order, and reader variation. METHODS: We studied 30 patients with unilateral tibiofemoral OA selected to represent a broad range of radiographic changes. Joint space width (JSW) was measured on plain anteroposterior weight bearing radiographs. Using an experimental design, 3 readers assessed JSW 3 times with 4 measuring instruments (ruler, caliper, graduated magnifying glass, digitized assessment). RESULTS: Intra and interobserver reproducibility was high with all measuring instruments (intraclass correlation coefficients from 0.95 to 0.98 and from 0.91 to 0.97, respectively). Analysis of variance (ANOVA) showed a patient effect (p < 10(-6)), a reader effect (p = 0.0001), an instrument effect (p = 0.0001), and a session order effect (p = 0.04). The variance component estimates were patients 55%, readers 34%, session order 2%, instruments 8%. ANOVA performed separately for each instrument showed that session order differences always represented less than 1% of the total variance. The reader component accounted for 0% of the total variance for the ruler, 2% for the digitized method, 16% for the caliper, and 18% for the graduated magnifying glass. CONCLUSION: Ruler and digitized assessment have better reliability than caliper and graduated magnifying glass.

Analysis of Variance↗
PubMed1996

Radiographic assessment of knee osteoarthritis: reproducibility and sensitivity to change.

OBJECTIVE: To determine the cross sectional and longitudinal reproducibility of various measures used for assessing radiographic knee osteoarthritis (OA) and to compare the sensitivity to change over a one year period of these measures. METHODS: We studied 55 patients referred to hospital with knee OA (clinical and radiographic ACR criteria). Anteroposterior radiographs at baseline and after 12 months were read by methods both qualitative (Kellgren and Lawrence grading scale, joint space narrowing scale) and quantitative (joint space width measurement at 3 different points). All qualitative methods used standardized atlases. The intraclass correlation coefficient and the graphical method of Bland and Altman were used to assess cross sectional and longitudinal reproducibility. Reproducibility was tested using 2 readers (interreader) and 2 readings for one of the readers (intrareader). Sensitivity to change was assessed using standardized response mean (SRM). RESULTS: All methods tested were shown to be reproducible both for cross sectional and longitudinal data. Intrareader was higher than interreader reproducibility for most radiographic features. Significant changes were observed after one year for methods measuring joint space narrowing. The sensitivity to change of the methods assessing joint space narrowing (joint space narrowing scale and joint space width measurement) was higher, with SRM varying from 0.37 to 0.57, than for the Kellgren and Lawrence grading system (SRM 0.19 and 0.23). CONCLUSION: These data suggest that methods measuring narrowing should be preferred as outcome measures in clinical trials or longitudinal epidemiologic studies; and show that in a particular subset of patients with very active disease, significant radiographic changes in knee OA can be detected after a one year period.

Aged↗
PubMed1996

[Treatment of hypertension with indapamide 1.5 mg sustained-release form: synthesis of results].

In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release form of indapamide was developed so as to optimize the safety/efficacy ratio, while maintaining a once-daily administration. The new formulation ensures that the active ingredient release occurs in a sustained manner over 24 hours, with mean concentrations close to the maximal concentration over a prolonged period, while avoiding peak plasma concentrations. Clinical data were obtained mainly through two European multicenter, randomized, double-blind trials, totalling 690 patients. Firstly, the antihypertensive efficacy' of the new indapamide 1.5 mg form was demonstrated by measuring blood pressure 24 hours after the last drug intake, using a mercury sphygmomanometer; the equivalence of its antihypertensive efficacy with the immediate-release form of indapamide 2.5 mg was then verified. Biochemical safety data showed better acceptability with indapamide 1.5 mg with in particular a reduction of more than 50% of the number of patients with kalemia < 3.4 mmol/l; clinical safety data confirmed the good acceptability observed with the 2.5 mg immediate-release form of indapamide since many years, especially regarding glucose and lipid neutrality. In conclusion, the 1.5 mg sustained-release form of indapamide has an improved antihypertensive efficacy/safety ratio which is in accordance with international recommendations for the usage of low doses of antihypertensive drugs and diuretics in the first-line treatment of hypertension.

Adolescent↗
PubMed1995

Adjuvant radiotherapy versus combined sequential chemotherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma. A randomized trial of 267 patients. GETCB (Groupe d'Etude et de Traitement des Cancers Bronchiques).

BACKGROUND: The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question. METHODS: From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients). RESULTS: The sex ratio (M:F) was 19/1; mean age was 57 +/- 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival. CONCLUSIONS: The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group.

BACKGROUND: Intensive chemotherapy for acute myelogenous leukemia (AML) continues to yield low rates of complete remission and survival among patients over the age of 65 years. Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy. We determined the effect of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) on mortality at eight weeks (the main end point) and the rate of complete remission among patients with AML who were 65 years old or older. METHODS: After induction chemotherapy with daunorubicin (45 mg per square meter of body-surface area per day for 4 days) and cytarabine arabinoside (200 mg per square meter per day for 7 days), 173 patients with newly diagnosed AML were randomly assigned on day 8 to receive either lenograstim (5 micrograms per kilogram of body weight per day) or placebo, starting on day 9, until there was neutrophil recovery or a treatment failure, or for a maximum of 28 days. Salvage chemotherapy was also followed by lenograstim or placebo. Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo. RESULTS: The mortality rate at eight weeks was similar in the lenograstim and placebo groups (23 and 27 percent, respectively; P = 0.60), as was the incidence of severe infections. The median duration of neutropenia (absolute neutrophil count < or = 1000 per cubic millimeter) was shorter in the lenograstim group (21 days, as compared with 27 days in the placebo group; P < 0.001). Eight percent of the patients in both groups had regrowth of AML cells. The rate of complete remission was significantly higher in the lenograstim group (70 percent, as compared with 47 percent in the placebo group; P = 0.002). Overall survival, however, was similar in the two groups (P = 0.76). CONCLUSIONS: The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years. The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo. Nevertheless, the overall survival in the two groups did not differ significantly.

Adjuvants, Immunologic↗
PubMed1995

[Chemotherapy of small cell bronchial cancers. Prognostic importance of complete response (1,280 patients). Groupe Petites Cellules].

OBJECTIVE: Pretherapeutic prognostic factors for patients given chemotherapy for small cell lung carcinoma have been widely studied. We evaluated response to chemotherapy in patients included in 4 multicentric trials with less restrictive entry criteria in order to determine the contribution of clinical outcome as a predictive factor. METHODS: Pretherapeutic and therapeutic prognostic factors were assessed in 1280 patients included in 4 successive multicentric therapeutic trials on chemotherapy for small cell lung carcinoma conducted from January 1, 1983 to April 1, 1992. Logrank test for univariate analysis and Cox's stepwise method for multivariate analysis were used to evaluate the results. RESULTS: Univariate analysis identified pretherapeutic factors as significant for prognosis: Karnofsky index (p < 0.0001), alkaline phosphatase level (p < 0.0002), white cell count (p < 0.0005), age (p = 0.0007), presence of brain metastasis (p = 0.0004), presence of liver metastasis (p = 0.03), initial extension (p = 0.04). Multivariate analysis taking into account pretherapeutic and therapeutic factors demonstrated that complete response after the second and after the sixth treatment session were predictive of longer survival (p = 0.0001). This factor was more powerful than all the pretherapeutic factors including the Karnofsky index, initial extension and brain metastasis. CONCLUSION: For patients with small cell lung carcinoma, the prognostic value of early response to chemotherapy suggests that high-doses should be used starting at the first session.

Adult↗
PubMed1995

Early predictors of outcome for HIV patients with neurological failure.

OBJECTIVE: To carry out a descriptive study of human immunodeficiency virus (HIV)-infected patients admitted to an intensive care unit (ICU) with neurological failure and to identify parameters that are predictive of death within 3 months. DESIGN: Case series study. POPULATION AND SETTING: A total of 84 consecutive HIV-infected patients admitted to an infectious disease ICU in a university hospital for neurological failure. A thorough clinical, laboratory, and brain computed tomography (CT) scan workup was done within 48 hours of admission. MAIN RESULTS: The mean (+/- SD) CD4+ lymphocyte count was 0.067 (+/- 0.086) x 10(9)/L. Mechanical ventilation was necessary within 48 hours of admission in 67 cases (80%). The brain CT scan revealed abscesses in 51 patients (61%). The abscesses were attributed to probable toxoplasmosis in 47 patients. A total of 57 patients died, yielding a 3-month survival rate of 32%. By the log-rank test, the following factors were predictive of death within 3 months of admission to the ICU: Glasgow Coma Scale score less than 7 (P = .01), signs of brain stem involvement (P = .001), and need for mechanical ventilation in the 48 hours after admission (P = .02). In a Cox model, only Glasgow Coma Scale score less than 7 (P = .006) and clinical signs of brain stem involvement (P = .02) were predictive of death within 3 months of admission to the ICU. CONCLUSIONS: Despite a thorough examination, no initial HIV-specific parameters were identified as predictive of death. The prognostic factors found simply reflected the severity of neurological involvement in the various etiologies.

AIDS Dementia Complex↗
PubMed1995

Clinico-pathological features and survival of lung cancer patients in Paris, France.

We studied the clinico-pathological features of 750 lung cancers identified in Paris, France, during 1988. An internal comparison was performed between adenocarcinomas and other subtypes. Survival of 502 patients was studied. 85% of patients were males; 93% were smokers or ex-smokers. Squamous cell carcinomas, adenocarcinomas, small cell carcinomas and large cell cancers accounted for 51, 22, 15 and 12% of all cases, respectively. Differences were found for the distribution of histological subtyping according to sex (P = 0.001) and smoking status (P = 0.0001) with a greater proportion of adenocarcinomas for women and non-smokers. Median overall survival was less than one year. In multiple regression analysis, small cell lung cancer patients appeared to have a worse prognosis than other histological subtypes. This study describes patients who were treated in community practice and might be more representative of the real clinico-pathological profile of this disease in France.

Adult↗
PubMed1995

Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision.

We carried out univariate and multivariate analysis of outcome among 122 patients with prosthetic valve endocarditis (PVE) admitted to our ICU between 1978 and 1992. The predominant pathogens were Staphylococcus aureus (33%), streptococci (20%), coagulase-negative staphylococci (12%), enterococci (10%), and Gram-negative bacilli (9%). At 4 months, overall survival was 66% (42 deaths). Staphylococcus aureus was the main predictor of death (75% vs 15% with other pathogens). In S aureus PVE, multivariate analysis identified the following predictors of death: prothrombin time < 30% (relative risk [RR]: 8.3), concomitant mediastinitis (RR: 4.9), heart failure (RR: 4.4), and septic shock (RR: 2.6). In PVE due to other pathogens, prothrombin time < 30% (RR: 32.26), renal failure (RR: 7.31), and heart failure (RR: 6.07) were associated with death. In S aureus PVE, survival was higher in patients who received medical-surgical therapy than in those who received medical therapy alone (9/20 [45%] vs 0/20) (p < 0.01). In PVE due to other pathogens, there was no difference in survival between patients who underwent prosthesis replacement (89%) and those who received only medical treatment (81%). Among the 65 patients who underwent heart surgery, the mortality rate and incidence of postoperative paravalvular leakage did not correlate with positive prosthesis cultures. We conclude that non-S aureus and uncomplicated PVE may be managed without valve replacement but that prompt surgical intervention should be required in all other situations.

Adult↗
PubMed1995

Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.

Adult↗
PubMed1995

Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial.

OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short-term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy.

Adult↗