Search PubMed⌕ Search

Biomedical subjects

A Mercatello

Publications and source records attributed to A Mercatello.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intensive regimen of cytokines with interleukin-2 and interferon alfa-2b in selected patients with metastatic renal carcinoma.

We conducted a Phase II trial using an intensive regimen combining interleukin-2 (IL2), interferon-alfa-2b (IFN), and lymphokine-activated killer (LAK) cells. The aim of this study was to evaluate the toxicity and the efficacy of this combination in selected patients with metastatic renal cell carcinoma. Thirty-one assessable patients were treated with at least one cycle of a regimen consisting of 20 x 10(6) IU/day s.c. IFN for 5 days, followed 2 days later by i.v. injections of 24 x 10(6) IU/m2/day IL2 every 8 h together with i.v. bolus of 5 x 10(6) IU/m2/day IFN every 8 h during 5 days. After a 6-day break, during which four leukophereses were performed, this i.v. combination was administered along with the LAK cell reinjections for a maximum of 5 days. Twenty-seven patients underwent the two parts of the first course of treatment; respectively, 42% and 46% of the planned dose of IL2 and IFN were administered. Several severe toxicities were observed including two treatment-related deaths. Significant tumor responses were observed in seven patients, including two complete remissions. Two of these patients remain alive without evidence of disease 36 and 40 months after treatment, respectively. This intensive regimen of IL2 together with IFN and LAK cells cannot be recommended even in selected patients with metastatic renal cell carcinoma. In addition, our results argue against the concept of a dose-response relationship in this setting.

Adult↗
PubMed1995

Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.

PURPOSE: Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS: We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS: All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION: These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.

Adult↗
PubMed1994

[Can hydroxyethylamidon be used during intensive care of brain-dead organ donors?].

In France, most of the kidney grafts are obtained from brain dead organ donors. Brain death induces numerous changes, especially in haemodynamic status, requiring the infusion of large volumes of fluid. The aim of this study was to evaluate the effect of hydroxyethyl starch (HES) on the organ donors and the kidney graft function in recipients. We compared two groups of brain dead organ donors and the kidney grafts, differing by the infused solutions: either a combination of HES (Elohes, Biosedra) and 4% human albumin solutions (HES group), or albumin alone in the control group (Albumin group). In the two groups, sex-ratio, age, cause of brain death and duration of therapy were similar. Fluid requirements were identical in the two groups: respectively 2,211 +/- 1,512 mL in the Albumin group vs 2,452 +/- 1,094 mL in the HES group (p = 0.17). However, the volume of albumin was significantly decreased in the HES group: 711 +/- 822 mL (p = 0.0001). Therefore the cost was lower in the latter: 638 +/- 633 vs 1766 +/- 788 FF. The coagulation status was not significantly different between the two groups. Amylasemia was higher in the HES group, but the difference was not significant. In the Albumin group, urinary output increased, but not significantly and creatinemia was decreased: 113.9 +/- 62 vs 131.5 +/- 44 mumol.L-1 (p < 0.05). The two groups of recipients were also similar for sex-ratio, age, kind of graft, cause of the chronic renal failure and ischaemia times.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Treatment of acute respiratory failure with non-invasive intermittent positive pressure ventilation in haematological patients.

OBJECTIVE: The aim of this study was to assess whether non-invasive positive pressure ventilation delivered intermittently (Ni-IPPV) by means of a facial or nasal mask is beneficial in haematological patients suffering from acute respiratory failure. DESIGN: Prospective, open, non-randomised study. SETTING: University Hospital, medical intensive care unit. PATIENTS AND METHOD: Eighteen haematological patients with acute respiratory failure which occurred before, during or just after therapeutic aplasia were ventilated with Ni-IPPV delivered via an individual nasal mask or a standard facial mask. Non-invasive ventilation was achieved until weaning (success (S)) or intubation (failure (F)). RESULTS: Twelve patients were ultimately intubated and died (F group). Seven needed intubation within 3 hours following admission because of the inability of Ni-IPPV to provide adequate ventilation in six patients and after cardiac arrest, probably related to cardiac aspergillosis in one patient. Six patients were not intubated and were discharged alive (S group). Of 11 patients who received Ni-IPPV for more than 3 hours, the respiratory rate decreased significantly (p < 0.05) from 33 +/- 7 breaths/min to 24 +/- 5 breaths/min with Ni-IPPV and the PaO2 increased significantly from 6.6 +/- 1.7 kPa upon admission to 17.7 +/- 5.5 kPa during Ni-IPPV. Mean daily ventilation was 12 +/- 7 hours for a mean duration of 5.5 +/- 4.4 days. Pressure support was used in nine patients and appeared the most efficient ventilation mode of non-invasive ventilation. The duration per day of Ni-IPPV was shorter and PaCO2 values during Ni-IPPV were lower in the S group than in the F group. CONCLUSIONS: This technique is able to provide adequate ventilatory support for many haematological patients and allows avoidance of ventilation in some.

Acute Disease↗
PubMed1993

[Treatment with cytokines of metastatic kidney cancer: the Lyon experience].

Between October 1987 and June 1992, 244 patients with metastatic renal carcinoma were referred to our Institute. One hundred and sixty-nine were included in immunotherapy protocols. The 40 most recent patients were included in the ongoing multicentric randomised Crecy study. The previous patients were treated with IL2 as a continuous infusion or high doses intravenous IL2 combined with alpha interferon (IFN) or a combination of IL2 and IFN as subcutaneous low doses. Some patients received as rescue treatment a combination of IL2 with Tumor Necrosis Factor (TNF). First line immunotherapy with cytokines gave 14-25% response rates in these patients with 5-10% of complete persistent remissions. The most intensive regimen was responsible for the most severe toxicity as well as the highest response rate. TNF does not appear to be of great concern since its systemic administration induced important limiting toxicities. This work emphasizes the need for prospective studies in order to evaluate the optimal mode and schedule of treatment as well as to investigate the impact of immunotherapy on survival.

Adult↗
PubMed1993

[Interleukin-2 immunotherapy and cutaneous manifestations].

The cutaneous manifestations which follow the administration of recombinant interleukin-2 (rIL-2) are well known, but their nature and severity have not yet been fully studied. The authors report the dermatological changes observed in 12 patients treated with rIL-2 for renal cancer. The predominant lesion was generalized erythema followed by desquamation.

Adult↗
PubMed1993

[Immunotherapy of metastatic kidney cancer].

Interleukin 2 (IL2), like Interferon alpha (IFN), is active in metastatic renal cancer, considered to be a chemoresistant cancer. 20 to 30% of objective responses, including 5 to 10% of complete remissions are reported with various protocols of IL2 administration. The considerable toxicity is now well controlled, allowing treatments to be administered in standard wards or even on an outpatient basis by subcutaneous injection. IFN, generally given as long-term treatment, achieved average response rates of between 15 and 20%. Although IL2 and IFN have been granted Product Marketing Authorization in France, the modalities of optimal administration, the place of the combination of IL2-Interferon alpha and the factors predictive of response to treatment still remain unclear.

Humans↗
PubMed1992

Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.

Adult↗
PubMed1992

[Treatment of renal cancer in adults with interleukin 2].

Interleukin 2 is active in metastatic renal adenocarcinoma which is usually considered as a chemoresistant tumour; 20 to 30% objective responses, including 5 to 10% complete remissions, are reported using various treatment schedules. Toxicity, though of great concern, is now controlled and IL2 is mostly used in standard oncology units or as an out-patient subcutaneous treatment. Even if IL2 is now a registered drug in France, many questions remain however, regarding the optimal schedule and dose, the interest of combining IL2 with interferon alpha or the predictive factors of response of this therapy.

Adult↗
PubMed1992

[Acute respiratory insufficiency in sickle cell disease].

Two cases are reported of acute respiratory failure occurring during sickling crises. In the first one, the crisis was characterised by priapism, and in the other one, by abdominal pain. The different causes of these respiratory effects are discussed: infection, fat embolism, pulmonary infarct, haemodynamic pulmonary oedema, as was probably the case in the first patient, or non haemodynamic pulmonary oedema due to sickling, as during conventional treatment of a sickling crisis (oxygen, antibiotics, blood transfusion, cytapheresis). Invasive investigations may contribute to keeping up the clinical picture, because of hypoxic sickling. The water equilibrium of these patients must be monitored with great care. Worsening of the patient's condition despite 48 h of correct treatment must lead to the search for a specific cause.

Acute Disease↗
PubMed1992

Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma.

The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2.

Aged↗
PubMed1992

Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer.

In this Phase I trial, the feasibility of sequential administration of continuous intravenous recombinant interleukin-2 (rIL-2) at 18 x 10(6) IU/m2/day for 6 days, followed by three daily bolus intravenous recombinant tumor necrosis factor (rTNF) infusions at doses escalating between 10 and 120 micrograms/m2/day, was investigated in 31 patients with metastatic malignancies. Prophylactic use of indomethacin prior to and during rTNF administration was found to significantly reduce toxicity. However, despite prophylactic indomethacin, a maximum tolerated dose of rTNF of 120 micrograms/m2 was reached. The limiting toxicity was hypotension. Predictable flu-like toxicities (i.e., fever/chills, hypotension, gastrointestinal toxicity, edema, malaise) were seen in most patients. These started during the rIL-2 infusion and continued during rTNF administration, particularly in the absence of indomethacin. Hematological, renal, and hepatic toxicities were not dose limiting. These toxicities were all reversible after treatment interruption. Pulmonary toxicity [i.e., anaphylactic-like reactions, bronchospasms, and adult respiratory distress syndrome (ARDS)] was seen in several patients immediately after rTNF infusions, irrespective of the rTNF dose or treatment cycle, and mainly in patients with extensive pulmonary metastases. The combined effect of treatment-related ARDS, lung metastases, and a Guillain-Barré syndrome led to the death of one patient. Two partial responses were seen in this study (i.e., breast and renal cancer). Based on these results, a Phase II trial of rIL-2 followed by rTNF has been initiated in metastatic breast cancer patients.

Adolescent↗