Biomedical subjects

B Escudier

Publications and source records attributed to B Escudier.

At least 19 recordsLinked to original sources

PubMed2000

Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alfa with or without fluorouracil. Groupe Français d'Immunothérapie, Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2a (rIFNalpha-2a) have been used extensively in the treatment of metastatic renal cancer. Most results, coming from noncontrolled phase II trials, showed inconsistent rates of response. More recently, the addition of fluorouracil (FU) was proposed to improve the efficacy of these regimens. PATIENTS AND METHODS: The role of a subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU was investigated. Patients were randomly assigned to receive a combination of rIL-2 and rIFNalpha-2a at weeks 1, 3, 5, and 7 or the same combination together with a continuous infusion of FU at weeks 1 and 5. The major end points of this multicenter, randomized trial were progression-free survival, response rate, and toxicity. Overall survival was a secondary end point. Tumor responses were reviewed by an independent committee. Analysis of the results was performed on an intention-to-treat basis. RESULTS: One hundred thirty-one patients were enrolled. There was no difference in toxicity between the arms, and no toxic death was observed. One partial response was observed in arm A and five in arm B. Progression-free survival did not differ between the arms, and rates at 1 year were 12% and 15% in arms A and B, respectively. No statistically significant differences were detected in any end point. CONCLUSION: The subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU does not benefit patients with metastatic renal carcinoma. Neither of these regimens can be recommended as standard treatment. The results of the subcutaneous cytokine regimen seem disappointing.

Adult↗

PubMed2000

Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas.

In this study, we showed that renal tumors contain substantial subsets of CD8(+) p58(+) T cells. From 1 of these tumors, T cells were amplified in mixed lymphocytes-tumor cell cultures and p58(+) T cells were selected immunologically. After expansion, phenotypic and functional features of p58(+) and p58(-) T cells were examined. The p58(+) T cells expressed p58.2 receptor and corresponded to CD3(+), CD8(+), T-cell receptor (TCR) alpha/beta(+) T cells that were CD56(+) and CD28(-). Functionally, p58(+) T cells showed a low level of lytic activity against autologous tumor cells that was dramatically and specifically increased by anti-p58.2 monoclonal antibody. On the other hand, p58(-) CD8(+) T cells did not lyse autologous tumor cells and had non-major histocompatibility complex-restricted cytotoxicity against K562 and Daudi cells. A p58(+) cytotoxic T lymphocyte (CTL) clone (4C7) with the same characteristics as the p58(+) T-cell line was derived. This CTL clone did not lyse autologous normal B cells but lysed several HLA-A1(+) renal tumor cell lines. Analysis of TCR repertoire diversity showed that the p58(+) T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58(-) T cells was polyclonal. Interestingly, TCR transcripts of p58(+) T cells and of CTL clone 4C7 were detected as prominent ex vivo in tumor cells but not in peripheral blood mononuclear cells, suggesting that these cells are antigen specific and amplified at the tumor site. (Blood. 2000;95:2883-2889)

Antigens, CD↗

PubMed2000

A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies.

PURPOSE: Gemcitabine and vinorelbine are active drugs with broad spectrum of activity and manageable toxicity in clinical trials. The aims of this study were to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of gemcitabine and vinorelbine to be recommended for phase II studies in patients with advanced cancers. PATIENTS AND METHODS: Drugs were given as 30-min infusions on day 1 and 8 (vinorelbine before gemcitabine) every 3 weeks. Thirty-six patients (male:female ratio 25:11; mean age 54, PS > 60) were treated including 1 retroperitoneal sarcoma, 7 head and neck, 10 lung, 4 thyroid, 6 pancreatic, 1 bladder, 2 ovary, 2 gastric, 1 rectum, 1 unknown primary, and 1 renal cell carcinoma. Doses of gemcitabine/vinorelbine ranged from 800/20 mg/m2 to 1500/30 mg/m2. RESULTS: The dose-limiting toxicity was neutropenia. A transient grade 2-3 elevation of transaminases was frequently observed at several dose-levels, although this toxicity did not appear to be dose dependant and was reversible at day 21 before the next cycle. Other toxicities were mild and easily manageable, consisting of fatigue and flu-like syndromes. Since the MTD was not reach at the higher dose-level, the recommended dose level of the gemcitabine-vinorelbine combination was 1500/30 mg/m2. One toxic death due to hematologic toxicity was reported in a heavily pretreated patient who underwent prior chemotherapy and pelvic radiotherapy. A total of 12 patients were treated at the recommended dose level which was associated with grade 3-4 neutropenia in 3 of 12 patients and in 22.9% of cycles. CONCLUSIONS: This study estimates that the recommended dose for phase II studies of gemcitabine-vinorelbine is 1500/30 mg/m2 at day 1 and 8 every three weeks. A careful monitoring of the hematologic toxicity is recommended in heavily pretreated patients and in patients who received pelvic radiotherapy. Partial responses observed in a patient with an advanced cisplatin-5-fluorouracil-resistant pancreatic adenocarcinoma and in a patient with mesothelioma support further evaluation of this combination in patients with tumors refractory to classical antitumor agents.

Adult↗

PubMed2000

Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients.

This study shows that subcutaneous administration of increasing doses of IL-12, once a week, in 21 cancer patients increased the expression of cytokine genes (interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IP-10, MIG, IL-10, IL-4) in peripheral blood mononuclear cells even at very low doses (30 ng/kg). Surprisingly, no circulating TNF-alpha or IL-4 could be detected in the plasma of patients treated with IL-12. However, a marked increase of soluble IL-4 receptor was demonstrated in the plasma of five of the six patients studied, which may represent an additional mechanism by which IL-12 inhibits the development of the Th2 response in vivo. A marked decline of IFN-gamma and IP10 induction was recorded after repeated cycles of IL-12. In contrast, in most patients IL-12 increased IL-10 expression with no subsequent decrease during the course of therapy, and even an earlier peak of IL-10 induction at the 6th cycle. In addition, a constant up-regulation of serum soluble IFN-gamma receptor levels was observed after each cycle of IL-12 treatment with a delayed peak compared with the IFN-gamma peak. The constant rise of IL-10 and soluble IFN-gamma receptor during IL-12 therapy may therefore contribute to the inhibition of IFN-gamma activity detected after repeated cycles of IL-12. Lastly, a marked heterogeneity of cytokine induction was observed from one patient to another, which appeared to be independent of the dose of IL-12 administered. These data may lead to a better understanding of the biological activity of IL-12 and the in vivo mechanisms of its regulation.

Antineoplastic Agents↗

PubMed2000

Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe.

PURPOSE: The median survival for patients with metastatic renal cell carcinoma (mRCC) is generally < 1 year. Immunotherapy with high-dose recombinant interleukin (IL)-2 has been reported to produce objective responses in approximately 15% of treated patients and is associated with durable complete responses and prolonged survival in responding patients. The impact of IL-2 therapy on survival of metastatic renal cell carcinoma patients has begun to emerge, based on long-term follow-up data from large databases. Combinations of IL-2 and interferon alfa (IFN-alpha) have also been intensively investigated in mRCC. PATIENTS AND METHODS: Between 1987 and 1990, 281 mRCC patients were treated with continuous infusion IL-2 in three European multinational, single-arm phase II trials. Long-term treatment outcomes for these patients were analyzed, and the results are presented here. The results of a large, randomized French cooperative group trial (the Cancer Renal Cytokine [CRECY] study) that enrolled 425 patients between 1991 and 1995 are also summarized. Patients on this trial were randomized to treatment with IL-2 alone, IFN-alpha alone, or the combination. RESULTS: Among patients included in the 281-patient database, the objective response rate was 15%. Median survival was 10 months; 41% of patients were alive at 1 year, 22% were alive at 2 years, and 8% were alive at 5 years. Among patients with a complete or partial response, 60% and 18% were alive at 5 years, respectively. No clinical factors were predictive for response or survival; however, no patient with a high endogenous IL-6 level at diagnosis responded to IL-2 therapy. The CRECY trial demonstrated that the combination of IL-2 and IFN-alpha induced a significantly higher response rate (P < 0.01) and significantly improved 1-year event-free survival (P = 0.01) compared with either agent alone, but overall survival was not significantly different between the three treatment groups. CONCLUSION: The European experience suggests that the 5-year survival rate for metastatic renal cell carcinoma patients treated with high-dose continuous infusion IL-2 therapy is approximately 8% and that the majority of the therapeutic benefit is restricted to patients achieving a complete response. Therefore, given the toxicity, candidates for IL-2 therapy should be carefully selected. The combination of IL-2 and IFN-alpha does not appear to provide additional survival benefit. Efforts to further improve therapeutic outcome for patients with metastatic renal cell carcinoma should focus on understanding the underlying mechanisms of cytokine-induced tumor regression.

Carcinoma, Renal Cell↗

PubMed2000

[Reliability of the response rate in oncology: analysis of the causes for variation].

We evaluated the impact of an evaluation committee (EC) on patients' overall response status in a large multicenter trial in oncology. We identified reasons for disagreements between investigators and the EC. The Cancer Renal Cytokine (CRECY) study was a French multicenter trial that tested cytokine therapy in 489 patients with metastatic renal cell carcinoma. Objective response (OR) evaluation included medical imaging and was studied according to international guidelines. A blinded peer review of all responders and litigious cases was performed by an EC. Major disagreements occurred in 43% and minor disagreements in 10.5% of the reviewed files. The number of significant tumor responses was reduced by 23.2% after review by the EC. Reasons for disagreements included errors in tumor measurements, errors in selection of measurable targets, intercurrent diseases, and radiologic technical problems. These reasons for disagreements are analyzed and discussed. We conclude that all therapeutic trial results should be reviewed by peer analysis of all presumed responders by an EC. International guidelines for response evaluation should be updated by including more reliable methods of measurements and definition of minimal imaging procedures.

Antineoplastic Agents↗

PubMed1999

Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.

Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases from colon or rectum carcinomas were randomly allocated to various daily doses of human recombinant IL-2 (from 0 to 12.10(6) units/m(2)). IL-2 was infused from day 7 to day 3 before hepatectomy and the conservation of a non-tumorous liver fragment in liquid nitrogen. Hepatic CYPs and monooxygenase activities were not significantly decreased in 5 patients receiving daily doses of 3 or 6 10(6) IL-2 units/m2, compared to 7 patients who did not receive IL-2. In contrast, in 6 patients receiving daily doses of 9 or 12 x 10(6) IL-2 units/m2, the mean values for immunoreactive CYP1A2, CYP2C, CYP2E1, and CYP3A4 were 37, 45, 60 and 39%, respectively, of those in controls; total CYP was significantly decreased by 34%, methoxyresorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%. These observations suggest that high doses of IL-2 may decrease total CYP and monooxygenase activities in man.

Adenocarcinoma↗

PubMed1999

Randomized trial of treatment with cisplatin and interleukin-2 either alone or in combination with interferon-alpha-2a in patients with metastatic melanoma: a Federation Nationale des Centres de Lutte Contre le Cancer Multicenter, parallel study.

BACKGROUND: The objective of the current study was to evaluate the response rate, survival, and toxicity of treatment with cisplatin and high dose intravenous continuous infusion interleukin-2 (IL-2) with or without interferon-alpha-2a (IFN) in patients with metastatic melanoma. METHODS: One hundred and seventeen patients with metastatic melanoma randomly were assigned to receive cisplatin, 100 mg/m2, followed after a 3-day rest period by IL-2, 18 x 10(6) IU/m2, on Days 3-6 and Days 17-21 (Arm 1) or cisplatin and IL-2 using an identical schedule plus subcutaneous IFN, 9 x 10(6) U, 3 times a week during IL-2 administration (Arm 2). In the absence of disease progression or undue toxicity, the cycle could be repeated on Day 29. Patients who responded after two cycles eventually could receive a third cycle. One hundred and one patients were evaluable for toxicity and efficacy. RESULTS: On treatment Arm 1, 3 patients (6%) achieved a complete response (CR) and 5 patients (10%) achieved a partial response (PR) with a median response duration of 3.8 months for the CRs and 8.7 months for the PRs. On treatment Arm 2, 2 patients (3%) achieved a CR (durations of 5.9 and 33.1 months, respectively) and 11 patients (21%) a PR with a median response duration of 8.3 months. The median durations of overall survival were 10.4 months (range, 1.1-39.7+ months) and 10.9 months (range, 0.5-38.1+ months) for treatment Arms 1 and 2, respectively. The toxicity profile was consistent with the known side effects of this IL-2 intravenous regimen combined with cisplatin chemotherapy and IFN. Toxicity was more pronounced in treatment Arm 2 compared with treatment Arm 1. There were 2 and 4 patients, respectively, in treatment Arms 1 and 2 who died within 28 days after completion of treatment. CONCLUSIONS: The observed overall response rates of 16% and 25% in treatment Arms 1 and 2, respectively, is lower than that expected with biochemotherapy; despite the fact that the objective of the trial was not to show any difference between the 2 treatment arms, our results indicate that the addition of IFN, at the dose and schedule used in this trial, fails to improve the activity of a cisplatin/IL-2 regimen significantly in patients with metastatic melanoma. Although response rates were relatively low, the median overall survival was nearly 1 year in both groups.

Adolescent↗

PubMed1999

Combination interleukin-2 and doxorubicin in advanced adult solid tumors: circumvention of doxorubicin resistance in soft-tissue sarcoma?

Based on the likelihood of antitumor interactions between cytokines and cytotoxic drugs, we designed a pilot study to evaluate feasibility, clinical, pharmacologic, and immunologic effects of concomitantly administered subcutaneous (SQ) recombinant interleukin-2 (r-IL-2) and doxorubicin (ADR) in patients with advanced solid tumors (AST). Patients received one injection of ADR alone (70 mg/m2) and 3 weeks later a combination of r-IL-2 (18 MIU/m2 days 1-5 s.q.) and ADR at the same dose either 3-4 h after the first r-IL-2 injection (arm 1) or 2 days after the last r-IL-2 injection (arm 2). The same combination was repeated every 4 weeks according to the evolution of the disease. Pharmacokinetics were assessed over 48 h after injection of ADR alone and after the first ADR-IL-2 cycle and immunologic monitoring at days 1 and 8 of the first ADR-IL-2 cycle. Tumors were measured at baseline, after ADR alone, and after each ADR-IL-2 cycle until progression. Twenty-one adult patients with various AST including 14 soft-tissue sarcomas (STS) entered the study, 11 in arm 1 and 10 in arm 2. All patients were heavily pretreated; 16 had received an anthracycline-containing chemotherapy regimen. Eleven patients were ADR refractory and 1 ADR resistant. Grade 4 neutropenia occurred in 28, 82, and 40% of patients after ADR alone, ADR-IL-2 in arm 1 and ADR-IL-2 in arm 2, respectively. Mucitis was higher in arm 1 (7 of 11 patients) compared with arm 2 (0 of 10) and ADR alone (0 of 21). SQ injections of r-IL-2 did not affect ADR pharmacokinetics. ADR injection in arm 1 prevented IL-2-induced lymphocyte rebounds in all patients but did not alter qualitatively non-major histocompatibility complex-restricted cytotoxicity. There was no response after ADR alone. Two patients, one in each arm, experienced a prolonged (8 and 5 months) objective response after ADR-IL-2. Both had ADR-refractory STS with a local relapse and metastatic metastases. Interestingly, both patients had unusually elevated TNF-alpha levels before and after the first ADR cycle. Combination ADR-IL-2, although toxic, is feasible and manageable with routine clinical support. r-IL-2 enhanced ADR hematologic and extrahematologic toxicities. The two objective responses observed in these heavily pretreated patients refractory to ADR supports the hypothesis of a modulation of ADR resistance, possibly mediated by means of a mechanism involving TNF-alpha. Elevated baseline TNF-alpha levels could be predictive of response to ADR-IL-2 and deserves further investigation.

Adult↗

PubMed1999

Cytokines in metastatic renal cell carcinoma: is it useful to switch to interleukin-2 or interferon after failure of a first treatment? Groupe Français d'Immunothérape.

PURPOSE: Interleukin-2 (IL-2) and interferon alfa-2a (IFNalpha2a) have some antitumor activity in metastatic renal cell carcinoma either alone or in combination. To determine whether either of these cytokines might be efficient after failure of the other, we analyzed a series of patients treated with either IL-2 or IFNalpha2a as second-line treatment after failure of the other cytokine. PATIENTS AND METHODS: We recently performed a large multicenter study to determine the respective efficacy of IL-2, IFNalpha2a, or combined treatment in renal cell carcinoma. In this study, patients who progressed on the single-arm treatment could receive the other cytokine in a cross-over trial. IL-2 was administered as a continuous intravenous infusion for 5 days (18 x 10(6) IU/m(2)/d), and IFNalpha2a was administered three times weekly at 18 x 10(6) IU. RESULTS: A total of 113 patients with progressive disease after first-line treatment received either IFNalpha2a (n = 48) or IL-2 (n = 65). Toxicity during second-line treatment was similar to that observed during first-line treatment. Only four partial responses were observed (one with IFNalpha2a and three with IL-2). All partial responders had a performance status of 0 and lung metastases. Moreover, three of these four patients had stable disease or had responded to first-line therapy. Only one patient with confirmed disease progression after receiving IL-2 subsequently responded to IFNalpha2a. CONCLUSION: Cross-over after failure of IL-2 or IFNalpha2a is poorly efficient in metastatic renal cell carcinoma, especially when progression has been clearly documented.

Adult↗

PubMed1999

Human renal cell carcinoma xenografts in SCID mice: tumorigenicity correlates with a poor clinical prognosis.

To establish human renal cell carcinoma (RCC) xenografts for preclinical studies, 55 renal tumors (33 primary and 22 metastatic lesions) were transplanted subcutaneously into severe combined immunodeficient mice. Twenty of 49 evaluable tumors (40.8%) grew with a median latency period of 89 days (36 to 209 days) from the day of engraftment. Tumor growth was stabilized after the fifth passage with a median time between passages of 38 days (19 to 80 days). Tumorigenicity was correlated with the metastatic phenotype of the tumor (54% success rate, p = 0.007) and with reduced survival of patients. Despite a possible evolution of histological features and tumor grading, established RCC xenografts were comparable to parental tumors, as assessed by karyotype and DNA-ploidy analyses. Molecular cytogenetic analysis also revealed specific genetic alterations characterizing distinct RCC types that were constant in parental and corresponding xenografts. In addition, this xenograft model has permitted the selection of minor tumor subclones with a proliferative advantage and minimal overexpressed chromosomal regions. We conclude that severe combined immunodeficient mice are useful recipients for the establishment of long-term RCC xenografts that can be used as valuable tools to evaluate the activity of new therapeutic approaches and to study biological parameters determining in vivo aggressiveness of human RCC.

Adult↗

PubMed1998

Prognostic factors for survival in patients with brain metastases from renal cell carcinoma.

BACKGROUND: Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4-6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation. METHODS: The clinical features of 68 patients who were treated at the Institut Gustave Roussy for brain metastases from renal cell carcinoma were collected retrospectively. Using univariate and multivariate analyses, a prognostic model based on independent prognostic factors was established. An external data set of 57 patients was used to validate the model. RESULTS: The median survival was 7 months. On univariate analysis survival was related significantly to the following adverse prognostic factors: no initial nephrectomy, left side and temporal location of brain metastases, presence of fever or weight loss, erythrocyte sedimentation rate > 50 mm/h, and time from initial diagnosis to brain metastases < or = 18 months. Multivariate analyses identified the previous variable as well as the presence of other visceral metastases as independent prognostic factors. Forty-four patients (65%) with no or 1 adverse prognostic factor (average risk group) had a median survival of 8 months and a 26% 1-year survival rate. Twenty-four patients (35%) with 2 adverse prognostic factors (poor risk group) had a median survival of 3 months and a 1-year survival rate of 9%. This model proved to be discriminant in an external data set; the median survival of patients assigned to the average risk group was 11 months (46% 1-year survival rate) compared with 4 months (9% 1-year survival rate) for patients assigned to the poor risk group. CONCLUSIONS: Patients presenting with brain metastases from renal cell carcinoma and poor risk prognostic factors are highly unlikely to benefit from medical treatments except symptomatic procedures. Conversely, the enrollment of patients with average risk prognostic factors into clinical trials dealing with chemotherapy or immunotherapy may be considered.

Adolescent↗

PubMed1998

Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie.

BACKGROUND: Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment. METHODS: Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis. RESULTS: Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P<0.01) for the groups receiving interleukin-2, interferon alfa-2a, and interleukin-2 plus interferon alfa-2a, respectively. At one year, the event-free survival rates were 15 percent, 12 percent, and 20 percent, respectively (P=0.01). There was no significant difference in overall survival among the three groups. Toxic effects of therapy were more common in patients receiving interleukin-2 than in those receiving interferon alfa-2a. Response to treatment was associated with having metastasis to a single organ and with receiving the combined treatment. The probability of rapid progression of disease was at least 70 percent for patients with at least two metastatic sites, liver metastases, and a period of less than one year between the diagnosis of the primary tumor and the appearance of metastases. CONCLUSIONS: Cytokines are active in a few patients with metastatic renal-cell carcinoma. The higher response rate and longer event-free survival obtained with a combination of cytokines must be balanced against the toxicity of such treatment.

Adjuvants, Immunologic↗

PubMed1998

Phase II study of interferon-alpha and all-trans retinoic acid in metastatic renal cell carcinoma.

Interferon-alpha is an accepted treatment for renal cell carcinoma, with a response rate approximately 14%. Retinoic acid has been claimed to improve such a response rate when combined with interferon. We present the results of a phase II study combining interferon alpha and all-trans retinoic acid (ATRA) in patients with metastatic renal cell carcinoma. Thirty-one patients who were not eligible for a trial of high-dose interleukin-2 treatment (because of low performance status: 7 patients; prior immunotherapy: 11 patients; age > 70: 8 patients, cardiac or respiratory failure: 4 patients; refusal for randomization: 1 patient) were enrolled in this study. Only one partial response was observed (3%). Despite the good tolerance observed with this association, ATRA does not improve the efficacy of interferon in this selected patient population (with poor prognosis). Such a treatment combination should not be further recommended in patients with metastatic renal cell carcinoma.

Adult↗

PubMed1998

Severity-of-illness scores for neutropenic cancer patients in an intensive care unit: Which is the best predictor? Do multiple assessment times improve the predictive value?

OBJECTIVES: To use three severity of illness scores to estimate the probability of hospital mortality among patients with cancer and neutropenia; to compare the performance of these scores, calculated at admission to an intensive care unit (ICU); and to test the improvement in estimation obtained by taking into account the first 72-hr period. DESIGN: Collection of data for every neutropenic patient hospitalized in the ICU during a 4-yr period. SETTING: A comprehensive cancer center. PATIENTS: Ninety-four patients were neutropenic at ICU admission. Their vital status was measured at hospital discharge. MEASUREMENTS AND MAIN RESULTS: The new Simplified Acute Physiology Score (SAPS) II improved the estimation of hospital mortality compared with the original SAPS score. Using a simple score based on the number of acute organ system failures (OSFs) to classify the patients, good discrimination between survivors and nonsurvivors was observed (area under the receiver operating characteristic curves, 79 +/- 5 [SD] %). The relationship between successive scores and outcome was explored using recursive partitioning. Patients were first classified according to their OSF value on the first day of hospitalization in the ICU with a cutoff of two organ failures, and classification was then improved by taking into account the OSF score on the third day. CONCLUSIONS: For cancer patients hospitalized in an ICU for a neutropenic episode, the severity of illness and the risk of death can be accurately assessed by the SAPS II score and the number of acute organ failures at admission. The OSF values on the first and third days of hospitalization both provided information, allowing the classification of patients into groups with different probabilities of hospital mortality.

APACHE↗

PubMed1998

Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie.

PURPOSE: A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks. RESULTS: The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment. CONCLUSION: This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.

Adult↗

PubMed1998

Overrepresentation of 7q31 and 17q in renal cell carcinomas.

Xenografts from four metastatic renal cell carcinomas (RCCs) were established in immunodeficient mice. All tumors exhibited cytogenetic features specific for the papillary subtype, namely, partial or total polysomy of chromosomes 7 and 17 and integrity of 3p. Cytogenetic analysis of the initial and xenografted tumors indicated that although clonal characteristics were consistently maintained in xenografts derived from metastases, a minor clone had been selected for in the xenografts derived from the primary tumors. Reverse painting and comparative genomic hybridization (CGH) allowed us to localize minimal overrepresented genomic regions to 7q31, where the MET protooncogene is located, and to 17q. Other overrepresented regions were 8q in all xenografts and Xq22-qter in three of them. The gain of genetic material from these regions may be a key factor ensuring the papillary nature of RCCs and their survival in xenografts.

Aneuploidy↗

PubMed1998

[Cancer of the kidney in the adult].

Renal cell carcinoma is a frequent disease. Recently, its incidence has been rising. Kidney tumors are detected more frequently by the newer radiologic techniques, but the diagnosis is steel difficult and occurs often late in the natural history of the disease. A high proportion of patients have metastases at diagnosis or after initial surgery. Many types of systemic therapy have been studied but resistance to radiotherapy and chemotherapy is the rule. There is a potential role for immunomodulation in the inhibition of tumor growth but clinical issue remain uncertain. In this review we discuss recent developments in epidemiology, histologic classification, tumor biology, methods of diagnosis, surgical techniques and immunotherapy for patients with metastatic disease.

Adult↗