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A Ravaud

Publications and source records attributed to A Ravaud.

At least 19 recordsLinked to original sources
PubMed2006

PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.

OBJECTIVE: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. METHODS: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. RESULTS: Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6-92.7) and the predictive positive value was 92.3% (95% CI: 64-99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. CONCLUSION: Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity.

Adult↗
PubMed2005

Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers.

In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3% [95% CI:17%-51%]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.

Adult↗
PubMed2003

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial.

The association of interleukin-2 (IL-2), interferon alpha-2a (IFNalpha), 5-fluorouracil (5-FU) has been reported to induce response in metastatic renal cell carcinoma (MRCC). This study evaluated IL-2, IFNalpha and 5FU as second-line treatment after failure under immunotherapy. A total of 35 patients received IL-2, at 9 x 10(6) IU m(-2), once or t.i.d, 5 days a week, every other week. Interferon alpha was administered at 6 MUI, TIW along with IL-2 every week. 5-Fluorouracil was given at 750 mg m(-2) day(-1) on days 1-5 every 4 weeks. One cycle lasted 8 weeks. All patients were evaluable for response and toxicity. There were two objective responses (5.7%) and 14 stable diseases (40%). Survival was 14 months. In all, 17 patients experienced grade 3 toxicity. The predictive factor for progression to second-line immunotherapy was the results of first-line immunotherapy, and performance status, delay from primary tumour to metastases and response or stabilisation to chemo-immunotherapy for survival. IL-2, IFNalpha and 5-FU induce low objective response but stabilisation in patients with MRCC having failed with immunotherapy, and may be considered only in selected patients on performance status, stabilisation or response after first-line immunotherapy and interval from their primary tumour to metastases.

Adult↗
PubMed2003

Phase II study of LU 103793 (dolastatin analogue) in patients with metastatic breast cancer.

LU 103793 is a synthetic analogue of Dolastatin 15 that inhibits tubulin polymerisation. The aim of this study was to evaluate the efficacy and tolerability of LU 103793 in patients with metastatic breast cancer who had been previously treated with two lines of chemotherapy for advanced disease. Patients received LU 103793 at a dose of 2.5 mg/m(2)/day over 5 min for 5 consecutive days every 3 weeks. Thirty-four patients were enrolled and 23 patients were eligible for the evaluation of efficacy. Eleven patients experienced grade 4 neutropenia. Other related grade 3/4 adverse events included asthenia (three patients), stomatitis (1), myalgia (1) and increase of serum bilirubin (2). The main toxicity was hypertension occurring in seven out of 34 patients. There were no objective responses, 7 patients had stable disease. These results do not support the further evaluation of LU 103793 in metastatic breast cancer patients using this dose and schedule.

Adult↗
PubMed2002

Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy.

Cytokine therapy for cancer or viral diseases is accompanied by the development of depressive symptoms in a significant proportion of patients. Despite the increasing number of studies on the neurotoxic effects of cytokines, the mechanisms by which cytokines induce depressive symptoms remain largely unknown. In view of the relationship between neurotransmitter precursors and mood, the present study aimed at assessing the relationship between serum concentrations of the amino acids tryptophan and tyrosine, major precursors of serotonin and norepinephrine respectively, and depressive symptoms in cancer patients undergoing cytokine therapy. Sixteen cancer patients eligible to receive immunotherapy with interleukin-2 and/or interferon-alpha participated in the study. At baseline and after one week and one month of therapy, depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), and blood samples were collected for the determination of the large neutral amino acids (LNAA) (tryptophan, tyrosine, valine, leucine, isoleucine, phenylalanine) which compete for transport across the blood-brain barrier. Serum concentrations of tryptophan as well as the tryptophan/LNAA ratio significantly decreased between baseline, one week and one month of therapy. The development and severity of depressive symptoms, especially anorexia, pessimistic thoughts, suicidal ideation and loss of concentration were positively correlated with the magnitude of the decreases in tryptophan concentrations during treatment. These findings indicate that the development of depressive symptoms in patients undergoing cytokine therapy could be mediated by a reduced availability of the serotonin relevant amino acid precursor, tryptophan.

Adult↗
PubMed2002

Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d'Immunothérapie.

Interleukin-2 (IL-2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results have been disappointing, with a majority of treatment failure. Over 6 years, the Groupe Français d'Immunothérapie enrolled 782 patients in successive multicenter trials using cytokine regimens. Univariate and multivariate analyses were performed on this large prospective database to identify prognostic factors for survival. The presence of biological signs of inflammation, short time interval from renal tumor to metastases (<1 year), elevated neutrophil counts, liver metastases, bone metastases, patient performance status (PS), the number of metastatic sites, alkaline phosphatases and hemoglobin levels were predictive of survival outcome. When compared with previous results, our study showed that PS, number of metastatic sites, disease-free interval, biological signs of inflammation and hemoglobin levels can be considered as validated prognostic factors. We also identified four independent factors predictive of rapid progression under cytokine treatment: presence of hepatic metastases, short interval from renal tumor to metastases (<1 year), more than one metastatic site and elevated neutrophil counts. Patients who combined at least three of these factors have >80% probability of rapid progression despite treatment. We think that these results must be taken into account when making the decision to treat with cytokine.

Adult↗
PubMed2001

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.

Adult↗
PubMed2001

Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy.

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.

Affect↗
PubMed2001

Lowered serum dipeptidyl peptidase IV activity is associated with depressive symptoms and cytokine production in cancer patients receiving interleukin-2-based immunotherapy.

There is some evidence that treatment with interleukin-2 (IL-2) and interferon-alpha (IFNalpha) frequently induces depressive symptoms and activation of the inflammatory response system (IRS). There is evidence that major depression is accompanied by lowered serum activity of dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5), a membrane-bound serine protease which catalyses the cleavage of some cytokines and neuro-active peptides and which modulates T cell activation and the production of cytokines, such as IL-2. This study was carried out to examine the effects of immunochemotherapy with IL-2 and IFNalpha, alone and together, in cancer patients on serum DPP IV activity in relation to changes in depressive symptoms and the IRS. The Montgomery and Asberg Rating Scale (MADRS), serum DPP IV activity, and the serum IL-6, and IL-2 receptor (IL-2R) concentrations were measured in 26 patients with metastatic cancers before and three and five days after treatment with IL-2 and IFNalpha, alone or together. Treatment with IL-2 with or without IFNalpha significantly suppressed serum DPP IV activity. The MADRS scores were significantly elevated by treatment with IL-2 with or without IFNalpha, but not IFNalpha alone. The immunochemotherapy-induced decreases in serum DPP IV were significantly and inversely correlated with the increases in the MADRS. Treatment with IL-2 alone or combined with IFNalpha also elevated serum IL-6 and IL-2R. There were significant and inverse correlations between the immuchemotherapy-induced decreases in serum DPP IV and the elevations in serum IL-6 or IL-2R. In conclusion, treatment with IL-2/IFNalpha decreases serum DPP IV activity within 3-5 days and the immunochemotherapy-induced decreases in serum DPP IV activity are significantly and inversely related to treatment-induced increases in severity of depression and signs of activation of the IRS.

Adult↗
PubMed2001

UFT and leucovorin in first-line chemotherapy for patients with metastatic gastric cancer. An Early Clinical Studies Group (ECSG)/European Organization for Research Treatment of Cancer (EORTC) phase II trial.

A phase II study was performed to evaluate 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) and leucovorin as first-line chemotherapy in European patients with advanced gastric cancer. From 38 patients, 25 were evaluable for response and 36 for toxicity. Patients received UFT at 300 mg/m(2)/day for 28 days, every 35 days and leucovorin at 90 mg/day on an identical schedule. Overall response rate was 10.5% (95% confidence interval (CI): 3.7-22.5%) in intent-to-treat analysis and 16% (95% CI: 5.7-33%) in evaluable patients. Grade 3-4 common toxicity criteria (CTC) toxicities were diarrhoea (28%; 10/36), nausea (11%; 4/36), vomiting (8%; 3/36) and asthenia (11%; 4/36). 23 patients in 44% (42/96) of the courses had to skip days of treatment due to toxicity or to non-compliance. In conclusion, UFT+leucovorin has a definitive, but low, efficacy in advanced gastric cancer patients. Toxicities were mainly gastrointestinal and treatment needs to be withheld if grade 2 diarrhoea occurs.

Administration, Oral↗
PubMed2000

In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates.

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.

Antigen-Presenting Cells↗
PubMed2000

Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy.

PURPOSE: Depressive symptomatology is frequently associated with interleukin (IL)-2 and interferon alfa-2b (INFalpha-2b) therapy in cancer patients. The objective of the present study was to evaluate the depressive and anxiety symptoms induced by IL-2 and/or INFalpha-2b in cancer patients during the first days of cytokine immunotherapy. PATIENTS AND METHODS: The study included 48 patients with renal cell carcinoma or melanoma. Patients were treated either with subcutaneous IL-2, alone (n = 20) or in combination with INFalpha-2b (n = 6); or with INFalpha-2b alone, administered subcutaneously at a low dose (n = 8) or intravenously at a high dose (n = 14). Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS), and anxiety symptoms were evaluated using the Covi scale. Evaluations were performed just before initiation of treatment (day 1) and on days 3 and 5 of treatment. RESULTS: Patients treated with IL-2 alone or in association with INFalpha-2b had significantly higher MADRS scores after 5 days of cytokine therapy, and patients who received both cytokines had increased scores on day 3. In contrast, patients treated with INFalpha-2b alone did not have varying MADRS scores during the course of treatment. Cytokine therapy had no effect on anxiety, except in patients treated with IL-2 in combination with INFalpha-2b. In these patients, the enhancement in anxiety scores that was observed on day 5 was mainly attributable to increased somatic complaints. CONCLUSION: IL-2 and INFalpha-2b have differential effects on mood, and IL-2 therapy induces depressive symptoms early in treatment.

Adult↗
PubMed2000

[Does surgery promote the development of metastasis in melanoma?].

Surgery, which is currently the only curative treatment for malignant melanoma, is suspected, in particular presentations, to induce adverse effects such as an increase of metastasis spread. A literature review was performed in order to examine the alleged causes of such phenomena. A medline search covering the 1985-1999 period was performed first. The chosen articles and the study of the references of each of them produced additional articles. The hypothesis is based on the alleged existence of tumor dormancy as micrometastates at an early stage of the disease. Surgery could induce metastasis spread directly by increasing the rate of circulating tumor cells and indirectly above all by disturbing complex mechanisms of tumor regulation such as the balance between activating and inhibiting factors of tumor angiogenesis. Surgery itself as well as the surgical stress could also make easier metastasis spread owing to antitumor immune mechanisms disturbance. Currently, there is no adequate evidence to induce a modified approach in the management of cutaneous melanoma. Surgery remains the mainstay of treatment. However, basic research on angiogenesis and immunity must be carried on.

Humans↗
PubMed1999

Taxane-induced glaucoma.

We report a case of glaucoma induced by doxetaxel therapy for metastatic breast cancer. The disorder recurred during treatment with paclitaxel.

Adult↗