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Biomedical subjects

T Philip

Publications and source records attributed to T Philip.

At least 19 recordsLinked to original sources
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

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

OBJECTIVE: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. MATERIALS AND METHODS: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design. RESULTS: Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Adult↗
PubMed2000

Induction chemotherapy in metastatic neuroblastoma--does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC).

The purpose of this study was to determine, from a review of published data, whether in stage 4 neuroblastoma in children over 1 year of age, the dose or scheduling of induction chemotherapy influenced the response rate in distant metastases. Publications relating to induction chemotherapy since the introduction of cisplatin/epipodophyllotoxin combinations were identified using Medline, Current Contents and personal reference lists. Thirteen publications were identified which described 17 regimens involving 948 children. The doses and the scheduling of the various regimens were compared with a standard regimen OPEC (vincristine, cisplatin, teniposide, cyclophosphamide). These were correlated with the reported response rates in the bone marrow. Due to a lack of standardisation in the nature of restaging investigations, timing of restaging and definitions of response it was difficult to compare all studies. The complete response rate at distant metastases ranged from less than 40% to over 90%. For individual drugs; the comparative doses given in each course ranged up to 4.2 g/m(2) for cyclophosphamide, 280 mg/m(2) for cisplatin, 600 mg/m(2) for etoposide and 4.5 mg/m(2) for vincristine. There was no evidence of any positive correlation between response rate in the marrow and either the dose of any individual drug or the schedule used. In contrast to a previous study which included a number of older studies where disease assessment was even more variable, this analysis has failed to show any justification for the routine use of very intensive induction regimens in this disease. Such an approach should only be taken in the context of randomised trials in which timing and methods of reassessment can be standardised. Until such studies demonstrate superiority either in terms of response rate or progression-free survival lower morbidity regimens should remain the standard therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Multivariable analysis of prognostic factors for toxicity and survival for patients enrolled in phase I clinical trials.

BACKGROUND: Patients with advanced solid tumors may be included in phase I clinical trials. In such studies, the benefit expected is generally lower than the likelihood of toxicity and may even be non-existent if the patient's life expectancy is too short. This study was performed to identify prognostic variables for toxicity and survival in patients who participate in phase I clinical trials. PATIENTS AND METHODS: One hundred fifty-four patients treated on a phase I clinical trial in our institute were evaluated retrospectively. Univariable and multivariable analyses of patients' characteristics were undertaken to determine their effects on the probability of grade 3 and 4 toxicity and on survival. RESULTS: Grade 3 or 4 toxicity was experienced by 56 patients (36%): dosage level at entry (P < 0.001) and age over 65 years (P = 0.03) were independently associated with the risk of toxicity. Median overall survival was 5 months. The multivariable analysis identified performance status 2 or 3 (P < 0.001) and lactate dehydrogenase levels greater than 600 UI (P < 0.001) as independent adverse prognostic variables for overall survival. Using these two parameters, we determined a prognostic index which allowed us to discriminate three risk groups of patients with an observed median survival of 8.5, 4.5 and 1.5 months, respectively. CONCLUSIONS: Subgroups with different survival expectancy can be identified among patients who are eligible for phase I clinical trials. If confirmed, the proposed prognostic model may be useful for therapeutic decision making in palliative oncology.

Adult↗
PubMed2000

First, build the foundations: practical considerations in general practitioner-mental health service liaison.

The co-working relationship between general practitioners and local mental health services lies at the heart of the success of recent changes in mental health care. These changes have seen large-scale deinstitutionalisation, a shift to primary and community care, and a government policy of prevention and partnerships. This article outlines a liaison project developed jointly by the South-East New South Wales Division of General Practice and the Southern Area Mental Health Service to address these issues. We describe the development of a protocol of basic standards which were practical, pragmatic and possible and, when fully established, would be the foundation of effective, efficient and efficacious shared care in mental health.

Australia↗
PubMed2000

LMCE3 treatment strategy: results in 99 consecutively diagnosed stage 4 neuroblastomas in children older than 1 year at diagnosis.

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P =.004). In the multivariate analysis, only age younger than 3 years at diagnosis (P =.0085) and achievement of complete or very good partial remission after NB87 and surgery (P =.00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P =.005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Economic impact of harmonizing medical practices: compliance with clinical practice guidelines in the follow-up of breast cancer in a French Comprehensive Cancer Center.

PURPOSE: The introduction of clinical practice guidelines (CPGs) and the increasing desire to harmonize clinical practices draw attention to the economic impact of these trends. In 1994, CPGs were introduced in a French Comprehensive Cancer Center (Centre Régional Léon Bérard, Lyon). We evaluated the application of these CPGs in addition to the consequences of harmonizing clinical practices with respect to the distribution of resources by specifically analyzing the posttherapeutic follow-up of patients with localized breast cancer. METHODS: A before-and-after analysis of the records of patients who received posttherapeutic follow-up for localized breast cancer as of either 1993 or 1995 was performed. Two hundred records were chosen at random, 100 from 1993 and 100 from 1995. Follow-up was continued for as long as possible and CPG compliance was studied for each year of the follow-up periods. RESULTS: Follow-up that was not CPG-compliant required a significantly greater amount of resources. This difference was due to neither consultations nor mammographies, but was due to other examinations that were systematically performed without any warning signs to justify them. Depending on the follow-up year, noncompliant follow-up cost the Social Security from 2.2 to 3.6 times more than compliant follow-up. A noticeable change in medical practices was observed after the introduction of CPGs in 1994. This was confirmed by a sharp decrease in mean Social Security expenditure per patient of more than one third between 1993 and 1995, regardless of the follow-up year considered. CONCLUSION: In the follow-up of patients with localized breast cancer, a large decrease in costs has been observed along with the evolution of medical practices toward CPG compliance. This finding is probably generalizable to other settings, but there is nothing that proves that it is applicable to other treatment strategies.

Aged↗
PubMed2000

A prospective study of the LMB regimen for diffuse large cell non Hodgkin's lymphoma in adults.

Although the CHOP regimen remains a standard first line chemotherapy for diffuse large cell lymphoma (DLCL) in adults, a majority of these patients will still experience disease progression after the completion of this treatment. The LMB protocol is an intensive chemotherapy regimen which yields high survival rates in Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL) in children, as well as in primary cerebral DLCL (PCL) of adults. Here, we report the long term results of this regimen in a prospective series of 22 adult patients with DLCL excluding PCL. Fifteen male and 7 female patients with a median age of 30 years (range: 20-55) were treated prospectively between 1988 and 1993. 16 (72%) patients had an age adjusted International Pronostic Index (IPI) > or = 1. The median duration of the treatment was 15 weeks (range 13-19). Nineteen of the 22 patients (87%) experienced an objective response (14 complete, and 5 partial responses) at the end of the protocol. The predominant toxicity was myelosuppression: 89% of the COPADEM courses were followed by grade IV neutropenia and 5% with grade IV infection. One patient died (4%) of treatment related toxicity. With a median follow-up of 94 months and a minimum follow-up of 65 months, 8-year overall and progression-free survival are 73% and 67% respectively. The 8 year overall survival were 100%, 78% and 42% in patients with an IPI 0, 1, and 2-3 respectively. This short intensive regimen yields promising long term survival rates in this monocentric prospective study and may deserve to be tested in a larger multicentric prospective study comparing it to the CHOP regimen.

Adult↗
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

[A study based on national DRG data to evaluate work load and practice relating to cancer patients in not-for-profit hospitals].

BACKGROUND: In France there is no reliable information describing the organisation of hospital care for patients with cancer. The present study attempts to clarify this issue taking advantage of an information source that has up to now been unused, namely the national PMSI (Information System Medical program) data base. METHODS: A quantitative study has been carried out regarding cancer management in France using information filed with the PMSI which compiles data related to hospital admissions in all institutions with more than 100 beds and subject to a defined global budget. The "cancer" component of hospital activity was extracted using a specific algorithm which utilized the diagnostic and intervention codes included in the admission summaries. By using the unit of activity as defined by the ISA (Activity Synthetic Index) and the scale of relative cost according to the GHM (Homogeneous Group of patients) it was possible to analyse the information in terms of a balance sheet. RESULTS: The study provided information regarding the costs and methods of management, including therapeutic strategies, for each type of hospital establishment. It is shown that with one death out of six, cancer covers a quarter of all hospital stays, and one sixth of annual hospital expenses. This accounts for 16.2% of ISA ie approximately 29 billion francs (4.6 billion dollars) for the public and semipublic sectors. Surgery, which accounted for 32% of expenditures, appeared to be the most expensive intervention, ahead of chemotherapy (16.3%) and radiotherapy (9.1%). Each type of hospital organisation (university, cancer centre, district hospital) had their own relative figures. CONCLUSION: Through this study the current situation regarding cancer care in hospital has been documented. It has also demonstrated the value of the PMSI data base as a source of information for large scale quantitative studies of health care economics. However, the PMSI does not yet provide details regarding infrastructure or succession of hospital stay. Ultimately, this analysis does not provide any information on the quality or efficacy of care but does define a typological system for health care organisations which could provide information on distribution of resources.

Costs and Cost Analysis↗
PubMed2000

[Huriet law: application in a regional cancer centre (Centre Léon-Bérard, Lyon)].

Clinical research is one of the main activities in cancer centres and is submitted in France to a specific law (named "loi Huriet") which includes good clinical practices. We are now conducting a general program of quality evaluation and improvement in the regional cancer centre of Lyon (centre Léon-Bérard). Part of this program is an audit of the application of the Huriet law. Since no instrument exist for measuring this application, we have created a specific one, that attribute notation according to the different aspects of the law. Results show a good level of conformity but sometime non sufficient. There is no difference between the two studied years. Quality changes according to promoters (private or academic) and monitoring. Written procedures and specific training for the different actors are required to improve quality of clinical research with focus on the patient interest.

Cancer Care Facilities↗
PubMed1999

Assessment of osteosarcoma response to neoadjuvant chemotherapy: comparative usefulness of dynamic gadolinium-enhanced spin-echo magnetic resonance imaging and technetium-99m skeletal angioscintigraphy.

The aim of this work was to study and compare the usefulness of dynamic contrast-enhanced spin-echo MR imaging with high temporal resolution hydroxymethylene diphosphonate technetium-99 m skeletal angioscintigraphy in predicting the osteosarcoma histological response to neoadjuvant chemotherapy. Twelve patients with resectable osteosarcoma were prospectively monitored with dynamic MR imaging and skeletal scintigraphy before start of neoadjuvant chemotherapy, after two cycles of therapy and before surgery. Neoplasm signal intensity and activity intensity were plotted against time, and slopes were calculated for percentage increase over baseline values in the first minute. Stability and increase in slope values during or after chemotherapy were defined as a "radiological non-response". Changes in slopes were compared with the "histological response" (Huvos grading). At midpoint of the chemotherapy, these two imaging modalities failed in predicting final histological response. After the completion of the chemotherapy, these imaging modalities allowed the prediction of histological response with the same accuracy (91 %). In this series, dynamic MR imaging and technetium skeletal scintigraphy provide similar results regarding the prediction of final histological response during neoadjuvant chemotherapy; these results cannot be used to modify the therapeutic protocol at midpoint of chemotherapy; these imaging tools predict accurately the histological response at the end of chemotherapy. These latter results may permit anticipation of the adjuvant chemotherapy strategy during decalcification procedures in resected osteosarcoma and thus to monitor chemotherapy in non-surgical osteosarcoma.

Adolescent↗
PubMed1999

Analysis of the eligibility of published economic evaluations for transfer to a given health care system. Methodological approach and application to the French health care system.

CONTEXT: Economic evaluations are costly and cannot always be carried out locally. Therefore, decision-makers may wish to use studies already performed in other settings. OBJECTIVE: To define a method for assessing the eligibility of published economic evaluations for transfer to a given health care system and apply it to the french health care system in the clinical situation of adjuvant therapy for women with breast cancer. METHODS: (1) Literature search in six databases from 1982 to 1996; (2) critical appraisal of articles based on four inclusion criteria; and (3) assessment of the eligibility of the studies for transfer based on five indicators. RESULTS: We identified 26 published economic evaluations concerning adjuvant therapy in women with breast cancer. Six (23%) met all four criteria used to select studies, but none of these studies were eligible for transfer to the french health care system. The main reason was that cost data was not reported in a transparent way. CONCLUSIONS: To improve the transferability of economic evaluations, we recommend that requirements for data provision in publications be standardized and international collaboration strengthened.

Bibliometrics↗
PubMed1999

High-dose methotrexate and HELP [Holoxan (ifosfamide), eldesine (vindesine), platinum]--doxorubicin in non-metastatic osteosarcoma of the extremity: a French multicentre pilot study. Fédération Nationale des Centres de Lutte contre le Cancer and Société Française d'Oncologie Pédiatrique.

UNLABELLED: This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery. PATIENTS AND METHODS: Sixty-two patients (39 males, 23 females: median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)-doxorubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP-doxorubicin. RESULTS: Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery; histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30-80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome. CONCLUSIONS: This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.

Adolescent↗