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J Y Blay

Publications and source records attributed to J Y Blay.

At least 19 recordsLinked to original sources
PubMed2002

Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Adult↗
PubMed2002

Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies.

The treatment of post-transplant lymphomas still needs major improvements in order to put the patient in remission and to retain graft function. Chemotherapy is far too toxic in these patients. A more specific treatment such as anti-B-cell monoclonal antibody is very promising. The cytotoxic effect of antibody relies mainly on complement-induced and antibody-dependent cellular cytotoxicity; apoptosis may also induce tumor cell death. B-cell antigens expressed on the cell surface are the targets of antibody attack; some specificities may be chosen because of their level of expression or because of signaling induced within the cell. Anti-B-cell antibodies can be produced by genetic engineering in order to be humanized or to carry bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal antibodies (mAbs) in transplant patients have been proven with different antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb. In a retrospective analysis of different centers in France, rituximab (anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate in 34 organ and bone-marrow transplant patients. But the conditions of use of antibody must be better defined, particularly with regard to the immunosuppressive therapy, the type of tumor and the dose of antibody. We must also improve our understanding of the in vivo mechanisms of action of antibody to develop more efficient antibody constructs.

Antibodies, Monoclonal↗
PubMed2002

Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

Gemcitabine (2'-deoxy-2'-difluorocytidine monohydrochloride) at a dose of 1250 mg/m(2) was given as a 30-min intravenous (i.v.) infusion on days 1 and 8 in a 3-weekly schedule to 32 patients with advanced soft-tissue sarcoma (STS) failing first-line chemotherapy. One patient was ineligible due to a delay between the previous chemotherapy and the start of treatment. Of the eligible patients, median age was 53 years (range 23-73 years). The predominant histological subtype was leiomyosarcoma in 12 patients (38%). The median number of cycles was three (range 1-8 cycles) with a median total dose of gemcitabine of 6.25 g/m(2) (range 1.25-19.97 g/m(2)). The relative dose intensity of gemcitabine was 96% (range 50-103%). Treatment was tolerated very well with non-complicated haematological toxicity as the most frequently observed side-effect. Only one partial tumour response was documented, giving a response rate of 3.23% (95% Confidence Interval (CI): 0.08-16.2%). The median overall survival was 268 days (95% CI: 129-377) and the median time to progression was 45 days (95% CI: 41-79). These results indicate that gemcitabine given at this dose and schedule is not active as second-line therapy in advanced STS.

Adult↗
PubMed2001

Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate.

PURPOSE: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. METHODS AND MATERIALS: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (> or =1 g/m(2)) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose (<3 g/m(2) vs.> or =3 g/m(2)), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose (<40 Gy vs. > or =40 Gy) was assessed in 70 irradiated complete responders. RESULTS: No difference in overall survival (OS) was detected between mono-CHT and combination CHT (p = 0.38). MTX > or =3 g/m(2) (p = 0.04), thiotepa (p = 0.03), and intrathecal CHT (p = 0.03) improved the OS, and nitrosoureas (p = 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX > or =3 g/m(2), only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of > or =40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. CONCLUSIONS: MTX > or =3 g/m(2) seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders.

Analysis of Variance↗
PubMed2001

Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas.

1-5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineated in a series of 1051 cancer patients receiving a first course of chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996 (CLB-1996 cohort), and then validated in a series of patients treated in the same department in 1997 (CLB-1997), in a prospective cohort of patients with aggressive non-Hodgkin's lymphoma (NHL) (CLB-NHL), and in a prospective cohort of patients with metastatic breast cancer (MBC series) receiving first-line chemotherapy. In the CLB-1996 series, 43 patients (4.1%) experienced early. In univariate analysis, age > 60, PS > 1, lymphocyte (ly) count 1 (hazard ratio 3.9 (95% Cl 2.0-7.5)) and d1-ly count <or= 700 microl(-1) (3.1 (95% Cl 1.6-5.8)) were identified as independent risk factors for ED. The calculated probability of ED was 20% (95% Cl 10-31) in patients with both risk factors, 6% (95% Cl 4-9) for patients with only 1 risk factor, and 1.7% (95% Cl 0.9-3) for patients with none of these 2 risk factors. In the CLB-97, CLB-NHL and MBC validation series, the observed incidences of early death in patients with both risk factors were 19%, 25% and 40% respectively and did not differ significantly from those calculated in the model. In conclusion, poor performance status and lymphopenia identify a subgroup of patients at high risk for early death after chemotherapy.

Adolescent↗
PubMed2001

IL-4 prevents the blockade of dendritic cell differentiation induced by tumor cells.

Malignant cells may escape from the immune response in vivo because of a defective differentiation of professional antigen-presenting cells (APCs), i.e., dendritic cells (DCs). We recently reported that tumor cells release interleukin (IL)-6 and macrophage colony stimulating factor (M-CSF), which inhibit the differentiation of CD34+ cells into DCs and promote their commitment toward monocytic lineage with a poor APC function. The results presented here show that both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional differentiation of CD34+ into DCs. IL-4 was found to act through a rapid blockade of the expression of M-CSF and the IL-6 receptor-transducing chain (gp130), along with a decrease of the secondary production of M-CSF, thereby preventing the loss of granulocyte macrophage colony stimulating factor (GM-CSF) receptor alpha chain expression on differentiating CD34+ cells. Consistent with these observations, the differentiation of DCs from monocytes cultured with GM-CSF and IL-4 was also impaired by RCC CM, but the minimal inhibitory concentrations of RCC CM were 10-fold higher than for CD34+ cells. In these conditions, monocytes cultured with GM-CSF and IL-4 also exhibited profound phenotypic changes (CD14+ D32+ CD86+ HLA-DR+ CD115(low) CD23(low) CD1a-) and a poor APC function. These alterations were overcome in a dose-dependent manner by IL-4 (5-500 IU/ml), although not beyond a 40% final concentration of RCC CM. The capacity of RCC CM to block DC differentiation from monocytes strongly correlated with IL-6 and M-CSF concentrations in medium. Taken together, these results demonstrate that IL-4 and IL-13 reverse the inhibitory effect of tumor cells on DC differentiation.

Antigens, CD↗
PubMed2001

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.

Adult↗
PubMed2001

Complete response of an HIV negative gastric Kaposi's sarcoma (KS) patient with peritoneal carcinomatosis by liposomal daunorubicin treatment.

We report the first case of an HIV negative patient with gastric Kaposi's sarcoma (KS) and peritoneal carcinomatosis in whom a complete response (CR) was obtained after liposomal daunorubicin administration. The patient presented with epigastric pain and hematemesis. Upper gastric endoscopy with multiple biopsies showed gastric involvement by KS. The whole physical examination and the thoraco-abdomino-pelvic CT scans showed no other localization. A total gastrectomy was performed. Histological examination confirmed the diagnosis of KS with involvement of regional lymph nodes and peritoneal lesions. Six cycles of liposomal daunorubicin were given. Post-treatment coelioscopic control was normal. The patient received another six adjuvant cycles of liposomal daunorubicin. The patient is in complete remission six months after the end of treatment. Liposomal daunorubicin is a promising treatment in the non HIV patient with visceral KS.

Adult↗
PubMed2001

Osteosarcoma.

Explore the source record for details and available documents.

Bone Neoplasms↗
PubMed2001

[High-dose chemotherapy in soft tissue sarcomas of adults].

Few cytotoxic agents are active for the treatment of soft tissue sarcomas of adults: drugs active in monotherapy are doxorubicin, ifosfamide, dacarbazine and ET743. In patients with advanced stage soft tissue sarcomas (ASTS), a dose-response relationship has been established for doxorubicin and ifosfamide. Intensive combination chemotherapy regimens at conventional doses (MAID, or AI) yield higher objective response rates than monochemotherapy regimens, ranging between 25% and 44%, but failed improve survival rates as comparted to less intensive regimens. Recently, several phase I or II studies have investigated the use of high dose chemotherapy regimens as consolidation therapy in ASTS in response to conventional regimens. HDCT regimens have been reported to yield response rates ranging between 18% and 66%. Some of these patients with ASTS achieved long term complete remission, in particular in the subgroup of patients in complete remission after conventional chemotherapy in advanced phase. Phase III studies are required to confirm that survival may be improved by HDCT in subgroups of patients with ASTS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Hodgkin's disease: biology can help the physician towards new prognostic factors and new therapeutic approaches].

Hodgkin's disease is a lymphoma pathology characterized, histology wise, by the presence of rare tumoral cells, known as Reed-Sternberg cells, in a polymorph, inflammatory and reactive cell environment. Recent studies in molecular biology have shown that the Reed-Sternberg cell is mainly derived from a post germinal B lymphoid cell. Reed-Sternberg cell is also known to express characteristic molecules of an antigen presenting cell. Paradoxically, Hodgkin's disease shows an intensive inflammatory reaction but activated immune cells are not efficient in this disease. The abnormal survival and proliferation rates of Reed-Sternberg cells are in relation with immune system escape, acquired mechanisms of apoptosis resistance and amplification of activation of NFkappaB in tumoral cells. If these observations allow a better understanding of the presentation and the evolution of this disease, they might lead to the determination of new prognostic factors and of specific therapeutic approaches.

Apoptosis↗
PubMed2000

[Standards, options, and recommendations for the use of hematopoietic growth factors in oncology].

Four hematopoietic growth factors have marketing approval in France: filgrastime (G-CSF), malgraostime (GM-CSF), lenograstime (glycolysated G-CSF) and erythropoietin. A standards, options and recommendations document has not yet been established for erythropoietin which is excluded from this report. Administration of hematopoietic growth factors can be proposed in five clinical situations: primary prophylaxis, secondary prophylaxis, curative care, after myeloablative chemotherapy and hematopoietic stem cell grafting, and finally mobilization of peripheral stem cells. Primary prophylaxis: excepting therapeutic trials, the use of hematopoietic growth factors is recommended for clinical situations where a significant incidence of neutropenia with fever has been reported in randomized trials and in rare cases where there is an increased risk of severe infectious complications. Hematopoietic growth factors are indispensable for increasing the quality of cytapheresis peripheral stem cell harvesting.

Antineoplastic Agents↗
PubMed2000

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults.

PURPOSE: Patients with metastatic or locally advanced, unresectable soft tissue sarcoma (ASTS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDCT) with hematopoietic stem-cell support in this disease is not established. PATIENTS AND METHODS: Between 1988 and 1994, 30 patients with ASTS who responded to a standard chemotherapy regimen were included in a prospective pilot study of HDCT as consolidation therapy using ifosfamide (12 g/m(2)), etoposide (800 mg/m(2)), and cisplatin (200 mg/m(2)) (VIC). RESULTS: The median duration of grade 4 neutropenia and thrombocytopenia was 14 and 10 days, respectively. Nineteen patients (63%) experienced grade 1 or higher renal toxicity. All eight patients in complete remission (CR) before HDCT were still in CR at day 60. Of the 22 patients in partial remission (PR) or with a minor response to conventional chemotherapy, CR, PR, and stable disease were achieved in four (18%), three (13%), and 12 patients (54%), respectively, by day 60, while three patients (14%) progressed. With a median follow-up of 94 months, overall and progression-free survival rates at 5 years after HDCT were 23% and 21%, respectively. Patients in CR before HDCT had a significantly superior 5-year overall survival rate compared with other patients (75% v 5%; P: =.001). CONCLUSION: Despite the toxicity of the VIC regimen, a high survival rate was observed in HDCT-treated patients who were in CR after conventional chemotherapy. A phase III randomized trial is required to establish the role of HDCT in ASTS.

Adolescent↗
PubMed2000

Research controversies in management of oral mucositis.

The management of mucositis is the subject of many controversies, and the optimal treatment is still not known. Several evaluation scoring systems have been described, but no one of these is appropriate to all clinical situations: a simple scale such as that devised by the WHO can be used routinely, and more sophisticated ones can be implemented by trained experimenters working in research. We have considered the impact of each of the treatments currently available on each stage of mucositis. In attempts at prevention, self-care, in the sense of oral hygiene, must remain atraumatic. It is probably advisable to differentiate patients with good previous oral care, in whom tooth brushing is beneficial, from others, in whom the risk of hemorrhage and infection excludes any brushing. Before the dosage of chemotherapy is reduced, the curative or palliative intent of the strategy must be carefully evaluated. In the vascular phase protection of the proliferating cells is attempted by means of vasoconstriction (cryotherapy), cytoprotection (prostaglandin E2 and other antioxidants) or epithelial cell-inhibiting factors such as TGF-B3. Treatments applied in the epithelial phase are directed at increasing the cell proliferation to accelerate epithelial restoration by sucralfate and several growth factors: hematopoietic GF, which has demonstrated a direct effect on the mucosa (GM-CSF), or epithelial growth factors such as keratinocyte GF. In the ulcerative and bacteriological phase attempts are made to attenuate sepsis by means of antiseptics (chlorhexidine), amphotericin B and antiviral agents or antibiotic lozenges. In the healing phase application of the low-energy helium-neon laser has demonstrably been followed by a later time of onset, less pronounced peak severity and shorter duration of oral mucositis. After cancer treatment, oral hygiene, inhibition of oral flora, and pain relief are the main goals. Physiopathogen-specific treatment is the next step, with the emphasis on the inhibition of epithelial cell proliferation during drug exposure and facilitation of epithelial maturation and healing.

Antineoplastic Agents↗