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Biomedical subjects

J M Andrieu

Publications and source records attributed to J M Andrieu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE: We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS: Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS: This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION: As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.

Adult↗
PubMed1997

[Subcutaneous administration of interleukin-2 in ambulatory treatment of patients with metastatic renal cancer. Three-year results of the SCAPP I program].

We report a french experience of subcutaneous administration of interleukin-2 in treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients with metastatic renal cell carcinoma were included in the study. During the 10-week induction period, interleukin-2 was administrated subcutaneously 5 days a week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, interleukin-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses with 1 complete response. A diminution of dose or interruption of treatment occurred with 7 patients because severe toxicity. Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. The median follow-up of all the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33% and 22% respectively. This multicentric trial confirms the efficacity of subcutaneously-administered interleukin-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. Unfortunately, increasing total doses of administrated interleukin-2 does not seem to increase efficacity according to response rate, but is more toxic.

Adult↗
PubMed1996

Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial.

BACKGROUND: This multicenter phase II trial was conducted in order to evaluate the efficacy and toxicity of the subcutaneous route of administration of rIL-2 in the treatment of patients with metastatic renal cell carcinoma and to check whether an increased cumulative dose of rIL-2 increases efficacy. PATIENTS AND METHODS: Thirty-nine patients with metastatic renal cell carcinoma were included in this study. During the induction period, rIL-2 was administered subcutaneously 5 days a week for 8 weeks. The weekly dosages were 90 MIU during weeks 1 and 6;63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, rIL-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. RESULTS: After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses (95% CI: 9% to 37%) with one complete response. Treatment was interrupted or reduced due to toxicity for seven patients: Neuropsychiatric symptoms (3 patients), joint pain (1 patient), major asthenia and anorexia (1 patient), stroke (1 patient), and septicemia (1 patient). Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. In none of the patients did the response status improve during this maintenance period. The median follow-up of all of the patients included was 19 months. The one- and two-year survivals were 65% and 33%, respectively, ad the median duration of response was 11 months (5 to 16+). CONCLUSIONS: This multicentric study confirms the efficacy of subcutaneously-administered rIL-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. The role of a maintenance therapy needs further evaluation.

Adult↗
PubMed1996

Mediastinal tumor size and response to chemotherapy are the only prognostic factors in supradiaphragmatic Hodgkin's disease treated by ABVD plus radiotherapy: ten-year results of the Paris-Ouest-France 81/12 trial, including 262 patients.

PURPOSE: To identify prognostic factors in 262 patients with supradiaphragmatic Hodgkin's disease (HD), clinical stages (CS) I and II, prospectively treated between 1981 and 1988 according to the Paris-Ouest-France (POF) 81/12 protocol by three 1-month cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus methylprednisone (ABVD-MP) followed by subtotal nodal irradiation (RT). PATIENTS AND METHODS: The size of mediastinal tumor (MT) was measured in all patients: 66 did not have MT (NoMT); 105 had a small-size MT (SSMT), ie, mediastinal mass ratio (MMR) less than 0.33; 58 had a medium-size MT (MSMT), ie, MMR > or = 0.33 and less than 0.45; and 33 had a bulky MT (BuMT), ie, MMR > or = 0.45. All patients received three cycles (CS IA, one cycle only) of ABVD-MP; patients in partial remission (PR) or complete remission (CR) after chemotherapy (CT) received supradiaphragmatic RT (involved fields, 40 Gy; adjacent fields, 30 Gy) plus lumboaortic and splenic RT (30 Gy); patients not in CR or PR after CT received salvage CT. RESULTS: Two hundred seventeen patients (82.8%) entered CR after CT and 258 (98.5%) after RT. Ten-year freedom-from-progression (FFP) and survival rateswere 88.6% and 89.4%, respectively. According to univariate analysis, MT size and post-CT status were the only factors to influence both FFP and survival. For patients with NoMT or SSMT, those with MSMT, and those with BuMT, FFP rates were 94.1%, 87.0%, and 63.0% (P < .001), respectively, while corresponding survival rates were 92.6%, 87.2%, and 78.2% (P < .05). FFP rates were significantly different between the patients who achieved CR and those who did not achieve CR after CT: 94.6% versus 65.3% (P < .001); corresponding survival rates were 89.9% and 73.7% (P < .01). Multivariate analysis confirmed that MT size and post-CT status were the only two prognostic factors for FFP; for survival, the same two characteristics, as well as age (< 40 v > or = 40 years), significantly affected prognosis. We were thus able to identify three groups. The 33 patients (12.6%) with a BuMT had 10-year FFP and survival rates of 63.0% and 78.2%, respectively. Of 229 patients without BuMT, the 195 who attained CR after CT had an optimal prognosis (FFP, 96.6%; survival, 93.6%), while those who failed to achieve CR after CT had an intermediate prognosis (FFP, 68.8%; survival, 77.6%). CONCLUSION: These results demonstrate the independent impact on HD prognosis of tumor burden and post-CT status.

Adolescent↗
PubMed1996

Infradiaphragmatic Hodgkin's disease: long term results of combined modality therapy.

Hodgkin's disease (HD) confined below the diaphragm accounts for less than 5% of all patients with HD. Although the major characteristics of this presentation appear established, optimal modalities of treatment still remain difficult to define. From April 1972 to October 1988, 28 patients with newly diagnosed infra-diaphragmatic HD, clinical stages I or II have been treated with 3 successive prospective protocols combining initial chemotherapy and radiotherapy (40 gy). This series of patients accounted for 4,3% of patients with HD limited to clinical stages (CS) I and II. Overall survival and freedom from relapse at 15 years were 74,4% and 73% respectively, without significant differences between clinical stages I and II, presence or absence of B symptoms or histologic subtype. There is only a trend (p < 0,10) in favour of patients younger than 40 years. In all 7 clinically staged IA patients no relapses were seen and combined treatment does not appear to be better than inverted Y irradiation alone. On the other hand initial chemotherapy seems necessary in patients with CS II A and B since 15 of our 21 patients are alive in first CR whereas the crude rate of transdiaphragmatic nodal relapses may reach up to 53% following radiotherapy alone.

Adolescent↗
PubMed1995

Long-term follow-up of HIV positive asymptomatic patients having received cyclosporin A.

The data of the 27 asymptomatic HIV-1 seropositive patients with CD4+ cell count between 300 and 600/microliters treated by Cyclosporin A (CSA) (7.5 mg/kg/day) in our institution between October 1985 and 1987 were reviewed in October 1993. Hemoglobin concentration, platelet count, total lymphocytes, CD4+ and CD8+ cell counts and serum core protein p24 antigenemia, as well as creatininemia measured before CSA onset, at CSA cessation and twice a year were recorded as well as clinical signs and CSA toxicities. In October 1993 median duration of CSA treatment was 11 months, median follow-up after CSA cessation was 45 months and median total follow-up was 67 months. Toxicities of CSA were those commonly encountered in other pathologies. Under CSA no patient progressed toward clinical AIDS (1987 definition). The mean CD4+ cell count of the 27 patients remained unchanged (gain of 1 cell/year) under CSA treatment, while it decreased at a rate of 50 cells/year after CSA cessation (p < 0,005). On the other hand CSA treatment had no significant impact on the evolution of total lymphocyte count, CD8+ cell counts, and P24 antigenémia.

Adult↗
PubMed1995

Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year.

Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.

Adult↗
PubMed1995

Glucocorticoids rescue CD4+ T lymphocytes from activation-induced apoptosis triggered by HIV-1: implications for pathogenesis and therapy.

OBJECTIVE: During HIV-1 infection, CD4+ T lymphocytes migrate to immune-reactive lymphoid organs where they are infected by the virus and/or killed by apoptosis on immunoregulatory stimuli--a potential mechanism underlying fatal CD4+ T-cell depletion observed in AIDS. This study seeks to determine the effects of glucocorticoids (GCC) on the activation-induced T-cell apoptosis triggered by HIV-1. METHODS: CD4+ and CD8+ T cells were purified from HIV-negative donor peripheral blood mononuclear cells (PBMC) by positive selection and exposed to HIV-1 (primary isolates). HIV-1-exposed CD4+ and CD8+ T cells as well as PBMC derived from HIV-1-infected patients were cultured with medium alone or anti-CD3 monoclonal antibodies (MAb)/mitogens in the presence or absence of hydrocortisone or prednisolone. Viral infection kinetics were assessed by polymerase chain reaction and viral replication was measured by p24 enzyme-linked immunosorbent assay. Cell survival, apoptosis, T-cell proliferation, blast cell transformation, and interleukin (IL)-2 receptor (CD25) expression were monitored in parallel for each cell population. RESULTS: Fractionated CD4+ T cells acutely infected by HIV-1 underwent apoptotic death on anti-CD3 MAb/mitogen stimulation. This activation-induced apoptotic cell killing was antagonized by pharmacological doses of prednisolone or hydrocortisone added up to 6 h after stimulation. GCC were also found to be capable of inhibiting the accelerated apoptosis in PBMC (including both CD4+ and CD8+ T-cell fractions) from HIV-1-infected patients. This anti-apoptotic action of GCC overbalanced their downregulatory effect on T-cell proliferation, resulting in an overall improvement of CD4+ T-cell survival in patient PBMC. These effects of GCC were abrogated by the anti-GCC RU 486 and were not associated with significant suppression of CD25 expression and IL-2-dependent T-cell blast transformation; moreover, GCC had no impact on viral infection and replication. CONCLUSION: GCC exert a receptor-mediated anti-apoptotic activity in mature T cells through both activation-induced and HIV-1-triggered pathways and could be potent inhibitors of T-cell apoptosis in HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country.

The link between Hodgkin's disease (HD) and Epstein-Barr virus (EBV) is well documented in childhood and here the same hypothesis has been examined in adults, by comparing cases from an industrialized and a developing country. In this study the prevalence of EBV markers in nodal lesions of adult HD were compared in 21 patients from France (Fr) and 25 from Algeria (Al), all clinically staged during 1990-1992. Median age was 29 years. Histologic subtypes included lymphocytic predominance (LP) Fr 1; nodular sclerosis (NS) Fr 16, Al 16; mixed cellularity (MC) Fr 4, Al 9. EBV markers examined included expression of latent membrane protein (LMP) in Reed-Sternberg and Hodgkin cells (RSC) by immunochemistry; EBV-DNA and -RNA in situ hybridization (ISH); EBV-DNA by polymerase chain reaction (PCR). Results showed that RSC were LMP-positive in 4 (2 NS, 2 MC) French and 7 (3 NS, 4 MC) Algerian. All LMP+ cases were also positive for EBV DNA-RNA ISH. ISH was positive in RSC of 33% of the French and 72% of Algerian patients (p < 0.02). The positivity was more frequent in MC (77%) than in other histologic types (45%). The EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). Conclusion. The discrepancy between PCR and ISH results may be due to the lesser sensitivity of the ISH technique, or, alternatively, to the presence of EBV in the lymphoid cells surrounding RSC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Human immunodeficiency virus associated Hodgkin's disease: report of 45 cases from the French Registry of HIV-Associated Tumors.

Clinical and pathological characteristics as well as outcome of 45 Hodgkin's disease (HD) cases collected by the French registry of HIV-associated tumors between January 1987 and December 1989 (all clinically staged according to the Ann Arbor system) were analyzed and compared with those of a cohort of 407 patients with clinical stages (CS) IA to IVB enrolled between September 1981 and August 1988 in a multicentric clinical trial. The route of HIV infection, initial CD4 cell count at the time of HD diagnosis and CDC class of HIV infection were studied as well as the progression to AIDS onset were recorded. HIV-HD is characterized by a predominance of advanced CS (75%), B symptoms (80%) and mixed cellularity histology (49%), as well as by early bone marrow involvement (24%); a specific feature is the rare occurrence of mediastinal involvement (13% in HIV-HD versus 71% in primary HD). With standard therapies, 79% of the patients achieved a complete remission, but hematological and infectious complications were very frequent. The proportion of intravenous drug abusers (IVDA) in HIV-HD (38%) is higher than in French HIV-infected population as a whole (20.8%). Median CD4 cell count was 306/microliters at the time of HD diagnosis, while only 5 cases (11%) were preceded by an AIDS manifestation; progression to AIDS rate was 94% at 2 years. Overall 2-year survival was 41%, with 71% for patients with an initial CD4 cell count over 300/microliters and 0% for those with CD4 cell count lower than 300/microliters (p < 0.01); opportunistic infections were the most frequent cause of death. HIV-HD seems to occur preferentially in.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

[Association of Epstein-Barr virus and Hodgkin's disease: comparison between Algerian and French patients].

The prevalence of Epstein-Barr virus (EBV) markers in nodal lesions from Algerian (Al) patients (n = 47) was compared to French (Fr) patients (n = 21) with Hodgkin's disease. Initial characteristics were: males Fr 57%, Al 53%; median age Fr 29, Al 26; histologic subtypes: lymphocytic predominance (LP) Fr 1, Al 2; nodular sclerosis (NS) Fr 16, Al 19; mixed cellularity (MC) Fr 4, Al 12; lymphocytic depletion (LD) Al 2. The latent membrane protein (LMP) was expressed in Reed-Sternberg cells (RSC) in 16 Al (4 NS, 12 MC) and 4 Fr (2 NS, 2 MC) cases. All LMP-positive cases were also positive by DNA or RNA in situ hybridization (ISH). ISH was positive in RSC of 29% of Fr and 66% of Al patients (p < 0.02); the positivity was more frequent in MC (80%) than in other histologic types (39%). EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). The discrepancy between PCR and ISH results can be due to a lesser sensitivity of the latter technique, or, alternatively, to the presence of EBV in lymphoid cells surrounding RSC. ISH positivity was more frequent in young Al adults than in Fr ones. This more pronounced HD-EBV link in patients from a developing country compared with an industrialized one can result from the age at primary EBV infection, which occurs earlier in Algeria than in France.

Adolescent↗
PubMed1994

Multi-target PCR analysis by capillary electrophoresis and laser-induced fluorescence.

Quantitative analysis of polymerase chain reaction (PCR) amplified HIV-1 DNA or cDNA fragments is attained using an automated system that combines capillary-gel electrophoresis (CGE) for high-efficiency separation and laser-induced fluorescence (LIF) for high-sensitivity detection. This system enables the detection of PCR-amplified multiple target DNA or cDNA in the same tube by a single injection with high precision.

Acquired Immunodeficiency Syndrome↗