PubMed Health⌕ Search

Biomedical subjects

P Carde

Publications and source records attributed to P Carde.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies].

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.

Cytarabine↗
PubMed1991

Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group.

OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease. INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials. Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy. MAIN RESULTS: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130). By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas. Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3. Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease. CONCLUSION: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggest the presence of aggressive and resistant Hodgkin disease. An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy.

Adult↗
PubMed1991

Therapeutic implications and sites of relapse predicted by elevated posttherapy erythrocyte sedimentation rate in early stage Hodgkin disease.

An analysis was performed of all 57 early relapses (ER) (within 18 months of therapy initiation) seen in a group of 301 patients treated on three successive European Organization for Research and Treatment of Cancer (EORTC) protocols from 1964 to 1981; to determine whether a posttherapy elevated erythrocyte sedimentation rate (ESR) (greater than or equal to 30 mm) could predict the type of relapse and the effect upon the relapse of different therapies received. Overall most ER occurred in extranodal (EN) (42%) or irradiated transdiaphragmatic nodal (TDN) (40%) sites. Compared to patients with normal posttherapy ESR (n = 12), patients with elevated posttherapy ESR (n = 45) had the same proportions of outfield and late relapses; more frequent multiple sites of ER (38% vs. 25%), increased proportions of early EN relapses (16% vs. 3%), TDN relapses (17% vs. 2%), and other ER (6% vs. 1%). ER were most frequently observed between 1964 and 1971, and "modern" radiotherapy (Rt) decreased ER overall from 27% to 13% and for elevated posttherapy ESR patients from 54% to 25%. When chemotherapy (Ct) was used as either adjuvant or initial therapy, ER were greatly reduced vs. Rt alone [overall (6% vs. 28%) and for patients with elevated posttherapy ESR (10% vs. 39%)]. Stepwise logistic regression showed Ct to be the most important factor "protecting" from EN relapse, but elevated posttherapy ESR was still significant. For early TDN relapse, elevated posttherapy ESR had the highest predictive value for relapse, greater than the types of radiation fields used and chemotherapy. An unexplained elevated posttherapy ESR, regardless of previous therapy, predicts for ER from aggressive HD, frequently in EN and irradiated areas, and warrants further early therapy.

Adult↗
PubMed1991

Management of relapse and survival in advanced stage Hodgkin's disease: the EORTC experience.

The EORTC Lymphoma Cooperative Group and the Pierre and Marie Curie Group conducted a multicentre randomised trial on clinical stages IIIB-IV Hodgkin's disease from 1981-1986. Two hundred seven patients were registered and 192 randomised. Actuarial survival at five years for the whole group was 68%. Induction chemotherapy with eight cycles of MOPP resulted in more patients with progressive disease and fewer partial responders than a combination of MOPP and ABVD, for an equal complete remission rate. Half of the partial responders went into complete remission after radiotherapy. At five years there was no significant survival difference between the arms. Progression was recorded in 39 patients of whom only 4 survived. Relapses were most frequent in previously involved unirradiated areas. For 46 relapsed patients, including 21 early relapses within 18 months of start of treatment, the four-year survival rate was 53%. When complete remission was reached, whether early or late with combination chemotherapy or after additional radiotherapy, prognosis was independent of the way in which it was achieved. All efforts should be taken to reach a complete remission for initially progressing patients and for partial responders.

Adolescent↗
PubMed1991

Alternating chemotherapy and radiotherapy combination for bulky stage I and II intermediate and high grade non-Hodgkin lymphoma: an update.

In 1980, based on experimental and clinical data, a protocol was developed at the Institut Gustave-Roussy (IGR), alternating eight monthly courses of chemotherapy (CHVP) and two, then three, radiotherapy sequences (15 Gy in 6 fractions and 10 days to the initially involved areas), for early stage unfavourable histology non-Hodgkin lymphomas (NHL). The results are updated for 55 selected patients presenting with bulky stage I and II NHL, intermediate and high grade according to the Working Formulation. Five-year overall survival rate was 69% and freedom from progression was 68%. Early haematologic and digestive tolerance was satisfactory, probably because a 10-15-day interval was respected between chemotherapy and radiotherapy and vice versa. No late toxicity was detected in 39 patients who presented with head and neck localizations; xerostomia was found to be only mild and transient. All patients given mediastinal irradiation experienced radiological mediastinitis, but functional impairment was usually moderate. One of the 4 patients who received 3 x 15 Gy radiotherapy courses to part of the abdomen, died of small bowel obstruction and perforation. The study demonstrated the feasibility of an alternated schedule of chemotherapy and radiotherapy, with satisfactory results in terms of long-term survival. However, the few late complications which were detected after irradiation of the abdomen or of the thorax led to an alteration of the initial scheme when these volumes are to be treated.

Adolescent↗
PubMed1991

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

Adolescent↗
PubMed1991

Pericarditis and myocardial infarctions after Hodgkin's disease therapy.

From 1971 to 1984, 499 patients with all stages of Hodgkin's disease received mediastinal irradiation at the Institut Gustave-Roussy by 25 MV photons from a linear accelerator. Thirty-five pericarditis (10-year cumulative incidence rate of 9.5%) and 13 myocardial infarctions (MI) (10-year cumulative incidence rate of 3.9%) were observed. In contrast, no cases were diagnosed in a parallel series of 138 Hodgkin's disease patients treated without mediastinal irradiation during the same period of time (p less than 0.005 for pericarditis, p less than 0.05 for MI). By multivariate analysis, the role of total radiation dose given to the mediastinum and that of fraction size were evaluated, adjusting for age, sex, mediastinal involvement, and type of chemotherapy. The pericarditis risk was significantly increased with total dose greater than or equal to 41 Gy (relative risk (RR) = 3.25, p = 0.006) and with dose per fraction greater than or equal to 3.0 Gy (RR = 2.0, p = 0.06). The myocardial infarction risk was not found to be related to total dose nor to fraction size in this series, possibly because of the small number of events.

France↗
PubMed1991

Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. The EORTC Lymphoma Group.

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Adolescent↗
PubMed1990

Immunoscintigraphy of Hodgkin's disease: in vivo use of radiolabelled monoclonal antibodies derived from Hodgkin cell lines.

The Hodgkin associated monoclonal antibody (Mab) HRS-1 reacts with Hodgkin and Reed-Sternberg cells (HR-S) in all HD subtypes. HRS-1 Mab was labelled with radioiodine and injected into 10 patients for immunoscintigraphy (IS). Seven patients were injected with HRS-1 Mab radiolabelled with 131I and three patients were injected with HRS-1 Mab labelled with 123I. A control anti-alpha-fetoprotein (anti-AFP) Mab was radiolabelled with another iodine isotope and was injected simultaneously in five cases. Six out of eight patients with proven HD had a true positive scan (nodal, splenic and bony involvement). Imaging was equivocal or failed in the two other patients. In the last two patients IS imaging was truly negative due to the absence of residual HD in one patient and to an erroneous histological diagnosis of HD in another patient. These results, although preliminary, demonstrate that IS with radioiodine-labelled HRS-1 Mab is feasible and may prove to be informative in the staging of HD.

Animals↗
PubMed1990

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

Adult↗
PubMed1990

Salvage therapy with methyl-gag, high-dose Ara-C, M-Amsa, and ifosfamide (MAMI) for recurrent or refractory lymphoma.

Thirty adult patients with relapsed or refractory malignant lymphoma underwent a Phase I-II trial of salvage chemotherapy combining methyl-gag, high-dose Ara-C, M-Amsa, and ifosfamide (MAMI protocol). All patients had been extensively pretreated. At the time of salvage therapy, 21 patients had visceral involvement and 23 patients were refractory. The overall response rate was 50% (11 patients in complete remission and 3 patients in partial remission). The main toxicity was myelosuppression; 4 treatment-related deaths occurred and 17 patients died of tumor progression with a median of 5 months. The MAMI protocol showed similar antitumoral efficacy to that of other salvage chemotherapy regimens used for poor prognosis malignant lymphoma but was more toxic. However, a response rate of 45% in refractory patients should be taken into account and this drug association deserves further investigation with regard to the selection of patients for bone marrow transplants.

Adolescent↗
PubMed1990

Chemotherapy of Hodgkin's disease.

Chemotherapy is the main treatment for advanced Hodgkin's disease as demonstrated by the NCI MOPP study. The main prognostic factors have been identified. ABVD is partially non cross-resistant and permits the alteration of two regimens in order to achieve greater efficacy. The respective impact of conventional and high-dose chemotherapy for salvage treatment is being evaluated. Long-term hazards due to different regimens require continuous assessment so that the choice and modalities of chemotherapy in localized disease may be determined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature.

The authors have reviewed 106 cases of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) treated at the Institut Gustave-Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5-year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P less than 0.001), the achievement of initial complete remission (CR) (P less than 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P less than 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.

Adolescent↗
PubMed1989

Radiolabeled monoclonal antibodies against Reed-Sternberg cells for in vivo imaging of Hodgkin's disease by immunoscintigraphy.

The Hodgkin Reed-Sternberg (HRS-1) monoclonal antibody (Mab) was raised against the L 428 Hodgkin's disease (HD) cell line. The HRS-1 Mab was labeled with radioactive iodine and injected into six patients with Hodgkin's disease of varied histological subtypes for immunoscintigraphic imaging. In five patients, the HRS-1 Mab was labeled with 131I; a control anti-alpha-fetoprotein (AFP) Mab was injected simultaneously in two of these five cases. Four of five patients had a positive scan (nodal, splenic and hepatic involvements), the results in the fifth patient being equivocal. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Although the immunoscintigraphy (IS) was performed secondary to effective chemotherapy, images of bony disease were demonstrated. These preliminary results demonstrate that IS with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value and the specificity of IS deserves confirmation in a larger series of patients. Several techniques such as the use of Fab or F(ab')2 fragments should further improve the results.

Adolescent↗
PubMed1989

Risk of secondary acute leukemia and preleukemia after Hodgkin's disease: the Institut Gustave-Roussy experience.

From 1960 to 1984, 871 patients were treated for Hodgkin's disease at the Institut Gustave-Roussy. Twenty-six percent of the cohort were treated with radiotherapy (RT) alone, 6% with chemotherapy (CT) alone, and 68% with a combination of RT and CT, either at first line or for salvage treatment. MOPP chemotherapy was given to 42% of the patients. Overall, 19 secondary acute leukemias or preleukemias were observed, 3 of them after extended RT alone, the other 16 after a combination of RT and MOPP. Among the alkylating agents used, only nitrogen mustard (mechloretamine) was shown in a multivariate analysis to be significantly associated (P less than 0.001) with an increased risk of secondary leukemia. A dose response was observed, with the risk relative to general population incidence rates being 45 in patients having been treated with 1-59 mg (total dose) of nitrogen mustard, 211 in those treated with 60-119 mg, and 636 in those treated with greater than or equal to 120 mg. No other factors were found to be associated with leukemia risk. The 10-year cumulative incidence of leukemia was zero in patients treated with limited RT alone, 2.4% in those treated with extended RT alone, 0% in those treated with a combination of RT and CT without nitrogen mustard, and 12.4% in those treated with RT + nitrogen mustard. Whether other alkylating agents give a similar result remains to be determined; these data suggest that the use of nitrogen mustard at a higher total dose than 60 mg is questionable in the treatment of Hodgkin's disease.

Adult↗
PubMed1989

Classical external indwelling central venous catheter versus totally implanted venous access systems for chemotherapy administration: a randomized trial in 100 patients with solid tumors.

A prospective randomized trial was organized at the Institut Gustave-Roussy to assess the reliability of classical external catheters (CE) versus totally implanted access systems (TI) for delivering intravenous chemotherapy for a duration of at least 6 months. The analysis was performed on the 96 patients whose implantation succeeded (CE 46, TI 50). Failure was defined as loss of ability to function (followed by removal) within the 6-month period of the survey. Patients dying with functional catheters were considered as censored (15 cases) at the time of death. Twenty-four access systems were removed. The removal-free curves differ significantly (P less than 0.001), favoring the TI access systems. The main reasons for removal were: catheter fall (CE6, (TI 0), migration (CE 1, TI 1), infection (CE 5, TI 1), thrombotic occlusion (CE 1, TI 0) and venous complications (CE 1 thrombosis plus 1 pulmonary embolism, TI 1 thrombosis). In addition, a survey by questionnaire demonstrated a significantly better patient activity rate (P = 0.02) and hygiene (P less than 0.001) in the TI group. This prospective randomized study demonstrates that totally implanted access systems are more reliable, safer and better tolerated than classical external catheters for solid tumor patients undergoing intravenous chemotherapy for longer than 6 months.

Antineoplastic Agents↗