Biomedical subjects

P Viens

Publications and source records attributed to P Viens.

At least 37 records · Page 2Linked to original sources

PubMed2003

Docetaxel and radiotherapy and pancreatic cancer.

PURPOSE: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of weekly docetaxel delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Thirteen patients with histologically proven locally non-resectable advanced adenocarcinoma of the pancreas were enrolled in this study. Patients received 4 weekly doses of docetaxel by 1-hour intravenous (IV) infusion with 40 Gy of external beam radiation therapy during 4 weeks. Patients who were stabilized or in response, received 2 additional cycles of docetaxel with a 10 Gy boost of radiotherapy. Doses were escalated at 10 mg/m2 increments in successive cohorts of 3 new patients until MTD was observed. RESULTS: Four patients received docetaxel at 20 mg/m2/week, 3 at 25 mg/m2/week, 3 at 30 mg/m2/week, and 3 at 35 mg/m2/week. All patients, except 2, were given the treatment in its integrity. The most common toxicities were nausea, vomiting, asthenia, and abdominal pains. Except for 1 patient, all toxicity was reversible and did not exceed grade 3. Hematologic toxicity was mild and has not required treatment interruption. 28% of the patients had to be rehospitalized. A total of 73 cycles was administered with a mean of 4 cycles per patient (2-6). CONCLUSION: Even the MTD was not reached, dose escalation was stopped at 35 mg/m2/week. This dose is comparable to the ones previously published using docetaxel in combination with radiotherapy in other tumors. Three patients achieved stable disease and 1 patient an objective response. This combination of weekly docetaxel and radiotherapy shows a feasible and well-tolerated regimen, with, nonetheless, a significant rate of rehospitalization, for patients with locally advanced pancreatic cancer.

Adenocarcinoma↗

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

Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation.

The importance of dose intensity has been strongly emphasized in high-risk breast cancer. Overexpression of erb B2 is clearly correlated with an overall poor prognosis which could be limited in patients receiving intensive chemotherapy with alkylating agents and autologous stem cell transplants (SST). Thirty-five patients with high-risk non-metastatic breast cancer (>4 involved lymph nodes), treated with high-dose chemotherapy (HDC) followed by SST were analyzed. All were previously treated by four cycles of standard-dose anthracycline or anthracene dione. Nine had erb B2 overexpression. Minimum follow-up duration was 41 months (median 68 months). At 5 years, the actuarial relapse-free survival is 57.4% and actuarial overall survival 67.4%. Patients with overexpression of erb B2 had significantly lower disease-free survivals (P: 0.021) and overall survivals (P: 0.001). On multivariate analysis, erb B2 overexpression appeared to be the single independent poor prognosis factor for relapse (RR 3.25, range 1.12 to 9.45) and overall (RR 5.28, range 1.74 to 16.03) survival. These results suggest that poor prognosis of erb B2 overexpression is unchanged after HDC with alkylating agents but a possible benefit may exist in these patients with the additional monoclonal antibody, herceptin.

Antineoplastic Agents, Alkylating↗

PubMed2002

Modulations of dose intensity of doxorubicin and cyclophosphamide in association with G-CSF and peripheral blood stem cells in adjuvant chemotherapy for breast cancer: comparative evaluation of completion and safety of three intensive regimens.

The aim of this study was to evaluate and to compare in terms of toxicity the modulations of dose intensity of cyclophosphamide and doxorubicin in adjuvant chemotherapy for high-risk breast cancer. Four cycles of sequential high-dose chemotherapy with doxorubicin and cyclophosphamide (AC), supported with G-CSF and peripheral blood stem cells (PBSC) were administered to 81 women. Three successive cohorts were studied: doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 21 days (group 1), doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 15 days (group 2), and doxorubicin (75 mg/m(2)) + cyclophosphamide (6000 mg/m(2)) every 21 days (group 3). Seventy-five patients received four cycles of treatment with a total of 310 cycles administered. The received dose intensity of doxorubicin was higher in group 2 and that of cyclophosphamide was lower in group 1 than in the other two groups. Hematological and extra-hematological toxicities, as well as the number and duration of hospitalizations for toxicity, were significantly higher in group 3. We conclude that the group 3 regimen is associated with toxicities comparable to autologous transplantation. Increasing dose intensity of doxorubicin and cyclophosphamide is feasible in an outpatient setting and safe in groups 1 and 2 with the support of hematopoietic factor and PBSC.

Adult↗

PubMed2002

Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients.

Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the real clinical efficacy of graft versus cancerous ovarian cells.

Adult↗

PubMed2002

Intensive sequential dose dense chemotherapy with stem cell support as first-line treatment in advanced ovarian carcinoma: a phase II study.

From August 1995 to December 1997, 15 patients with stage III-IV ovarian cancer were treated with outpatient intensive chemotherapy with G-CSF and stem cell support. The first cycle consisted of cyclophophamide IV 6 g/m(2); second, third, fourth and fifth paclitaxel 250 mg/m(2) and the sixth and seventh carboplatin AUC 18. CD34(+) cells were collected after the first cycle and reinfused after completion of cycles 6 and 7. Fourteen patients had stage IIIc and one patient had stage IV disease with liver metastases. All patients underwent laparotomy to maximize tumor debulking. This was optimal in eight patients and suboptimal in seven patients. Second-look surgery was performed in 14 patients. All patients had macroscopic complete responses and 10 patients had complete histologic response. Median follow-up was 48 months (range, 20 to 62). Twelve patients had further progression at a median of 27 months (range, 9 to 42) and nine are alive, three without evidence of disease progression. This pilot study shows that dose-dense chemotherapy with paclitaxel and carboplatin is associated with low toxicity and may improve the outcome of patients with poor prognosis ovarian cancer.

Adult↗

PubMed2001

Quality of life of breast cancer patients receiving high-dose-intensity chemotherapy: impact of length of cycles.

This study was designed to measure treatment side-effects and quality of life (QL) of 47 nonmetastatic breast cancer patients subjected to a dose-intensity increase while receiving a sequential high dose chemotherapy (doxorubicin+cyclophosphamide - 4 cycles). The dose-intensity increase was obtained by shortening the length of cycles from 21 to 14 days. Treatment side-effects were self-assessed in terms of frequency and associated distress in cycles 1 and 3 by using a specific side-effect self-report questionnaire (19 items). Multidimensional QL measurement was performed at inclusion and before the start of cycles 2 and 4, by using the EORTC QLQ-C30. Pain was evaluated by patients on a visual analogue scale at the same times as QL evaluation. Patients' self-ratings indicated that the total number of symptoms, the number of symptoms rated by patients as quite or very distressing, and symptom frequency were comparable whatever the length of cycle. Overall, although underestimating most patients' symptoms, physicians' reports provided similar results. However, analysis of multidimensional QL showed that, in comparison to standard administration of 4 cycles of 21 days, there was a more significant deterioration of the QLQ-C30 global QL score ( P=0.01) at the second cycle of chemotherapy and of the physical functioning score ( P=0.02) at the fourth cycle when the cycle length was reduced. This study, although limited by a small patient cohort, has shown that shortening cycles to increase dose intensity had relatively few consequences on adverse treatment effects but a highly negative impact on patients' quality of life.

Adult↗

PubMed2001

Gene expression profiling of cancer by use of DNA arrays: how far from the clinic?

DNA arrays allow the simultaneous analysis of expression levels for thousands of genes in normal and pathological tissues and hold great promise in molecular medicine, notably in cancer research. The great biological and clinical diversity present in human tumours is poorly characterised by the current classification systems. DNA arrays can provide a better understanding of oncogenesis, leading to improvements in cancer management. First, the identification of new target genes and pathways will allow the development of specific molecular-based anticancer drugs. Secondly, expression profiles will permit tumour classification in more homogeneous diagnostic and prognostic groups, as well as the identification of new clinically and biologically relevant tumour subclasses. Here, we review the technology and present some cancer studies with promising results. Finally, we discuss some of the issues that must be resolved in the near future, so that DNA arrays can fulfil the aims mentioned above.

Gene Expression Profiling↗

PubMed2001

High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT).

PURPOSE: to determine the outcome of epithelial ovarian cancer in patients registered with the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS AND METHODS: A retrospective analysis was performed on 254 patients with advanced or recurrent disease, median age 46 years (14-63) from 39 centres treated between 1982 and 1996. Only 25% of patients were known to have no or microscopic disease after initial surgery; in approximately 20% the disease status was unknown, the remainder had macroscopic disease. RESULTS: One hundred five patients received high-dose chemotherapy in complete or very good partial remission, twenty-seven in second remission and the remainder in the presence of residual disease. Most received melphalan or carboplatin, or a combination (86%) supported by autologous bone marrow or peripheral blood stem cells. The survival of patients treated in remission was significantly better than in other groups (median 33 vs. 14 months; P = 0.0001). The durability of remission was longer after transplantation in first remission than in second remission (median disease-free survival 18 vs. 9 months; P = 0.005). With a median follow-up of 76 months from diagnosis the median disease-free and overall survival in stage III disease transplanted in remission is 42 and 59 months and for stage IV disease 26 and 40 months. CONCLUSIONS: High-dose chemotherapy has a potential benefit for patients in remission. The results support the conduct of randomised studies to determine whether there is a real value from this treatment.

Adolescent↗

PubMed2001

Epirubicin--docetaxel combination in first-line chemotherapy for patients with metastatic breast cancer: final results of a dose-finding and efficacy study.

The aim of the study was to define a regular and tolerable dose of the epirubicin-docetaxel combination in first-line chemotherapy of patients with metastatic breast cancer. Sixty-five women with measurable and/or evaluable disease were treated with epirubicin escalated from 60 to 110 mg/m(2) according to 5 dose levels, in combination with a fixed dose of 75 mg/m(2) docetaxel, every 21 days for 6 cycles, without preventive use of hematopoietic growth factors or antibiotics. Forty-three women received adjuvant chemotherapy, consisting of anthracyline- or anthracenedione-based regimens in 39 cases (60%). Twenty-seven women were treated in the phase I study (3 at epirubicin 60 mg/m(2), and 6 at each subsequent dose level). Dose-limiting toxicity consisted of grade III asthenia and febrile neutropenia (epirubicin 75 mg/m(2)), grade IV thrombopenia and grade III asthenia (epirubicin 90 mg/m(2)), grade IV stomatitis and grade III diarrhea (epirubicin 100 mg/m(2)), and grade III diarrhea (epirubicin 110 mg/m(2)). In the phase II study, an additional 38 women were treated at epirubicin 90 mg/m(2) and epirubicin 100 mg/m(2). During the 349 cycles delivered, grade IV neutropenia occurred in 90%; febrile neutropenia requiring hospitalization occurred in 62 (17.8%) and lasted more than 3 days in 12 (3.4%). Nonhematologic toxicity was acceptable. Three left ventricular ejection fraction depressions occurred and normalized during follow-up. The overall response rate in the 62 evaluable women was 69.4% (range: 58--81%), with a median duration of 7.8 months. After 26 months of follow-up, the median time to progression was 9.1 months and median overall survival was 22.7 months. On the basis of efficacy and toxicity, the recommended dose of the combination is epirubicin 100 mg/m(2) plus docetaxel 75 mg/m(2).

Adult↗

PubMed2001

Detection of epithelial cells in hematopoietic organs of patients with breast cancer. Physiopathological significance and clinical consequences.

Breast cancer is the most frequent neoplastic disease in populations of developed countries. It will affect 1 of every 6 or 7 women during their lifetime. The disease eventually evolves to a metastatic stage, and currently appears to be not curable at that stage. Thus, understanding mechanisms that result in the establishment of tumor at sites distant from the primary location is of the utmost importance. Equally important is the definition of a metastatic state, especially in regard to the detection of micrometastases. Finally, the presence of circulating tumor cells in the peripheral blood of patients who undergo progenitor mobilization, collection and reinfusion may be of clinical significance in the setting of high-dose chemotherapy for breast cancer.

Bone Marrow↗

PubMed2001

Home care of malaria-infected children of less than 5 years of age in a rural area of the Republic of Guinea.

OBJECTIVES: To assess the ability of mothers in a rural area of the Republic of Guinea to identify fever in their children, and to estimate the proportion of children who received antimalarial drugs. METHODS: Children under 5 years of age in 41 villages were selected by a two-step cluster sampling technique. During home visits we examined the children and questioned their mothers about the child's symptoms and treatment. FINDINGS: Of 784 children examined, 23% were febrile and more than half of them also had a positive smear result for Plasmodium. Mothers reported 63% of children with a temperature > or = 37.5 degrees C as sick. Among all children reported as feverish by their mother, 55% had a normal temperature (< 37.5 degrees C). In contrast, a temperature > or = 37.5 degrees C was found in 38% of children identified as sick but afebrile by their mother and in 13% of children considered healthy. Among febrile children, 18% were given chloroquine at home or had consulted at the health centre or a dispensary. CONCLUSION: In areas where malaria is endemic, recognition of fever and its presumptive treatment with antimalarial drugs is an essential part of the strategy of the World Health Organization (WHO) to reduce the morbidity due to this disease. This population study shows that mothers often failed to identify fever in their children and to consult or to provide antimalarial treatment. Without great efforts to improve home care, it is unlikely that the morbidity and mortality due to malaria in young children will be greatly reduced.

Antimalarials↗

PubMed2001

Etiology of urethral discharge in West Africa: the role of Mycoplasma genitalium and Trichomonas vaginalis.

OBJECTIVE: To determine the etiological role of pathogens other than Neisseria gonorrhoeae and Chlamydia trachomatis in urethral discharge in West African men. METHODS: Urethral swabs were obtained from 659 male patients presenting with urethral discharge in 72 primary health care facilities in seven West African countries, and in 339 controls presenting for complaints unrelated to the genitourinary tract. Polymerase chain reaction analysis was used to detect the presence of N. gonorrhoeae, C. trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum. FINDINGS: N. gonorrhoeae, T. vaginalis, C. trachomatis, and M. genitalium--but not U. urealyticum--were found more frequently in men with urethral discharge than in asymptomatic controls, being present in 61.9%, 13.8%, 13.4% and 10.0%, respectively, of cases of urethral discharge. Multiple infections were common. Among patients with gonococcal infection, T. vaginalis was as frequent a coinfection as C. trachomatis. M. genitalium, T. vaginalis, and C. trachomatis caused a similar clinical syndrome to that associated with gonococcal infection, but with a less severe urethral discharge. CONCLUSIONS: M. genitalium and T. vaginalis are important etiological agents of urethral discharge in West Africa. The frequent occurrence of multiple infections with any combination of four pathogens strongly supports the syndromic approach. The optimal use of metronidazole in flowcharts for the syndromic management of urethral discharge needs to be explored in therapeutic trials.

Adult↗

PubMed2001

[Molecular typing of breast cancer: transcriptomics and DNA microarrays].

Breast cancer is the most frequent and deadly cancer of women. Its great heterogeneity makes prognosis and response to current treatments highly variable and difficult to predict. Mammary oncogenesis remains poorly understood. These issues should benefit from recent development of techniques capable of large-scale molecular analyses. The use of cDNA array techniques allows for the simultaneous analysis of the mRNA expression levels of thousands of genes in mammary tumor cell lines and breast tumors. Expression profiles will help classify tumors and provide new prognostic tools and potential therapeutic targets. They will also boost our knowledge of the molecular events responsible for the development and progression of this cancer.

Breast Neoplasms↗

PubMed2001

[High-dose chemotherapy with hematopoietic stem-cell support in breast cancer].

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Adenocarcinoma↗

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

Gene expression profiling of primary breast carcinomas using arrays of candidate genes.

Breast cancer is characterized by an important histoclinical heterogeneity that currently hampers the selection of the most appropriate treatment for each case. This problem could be solved by the identification of new parameters that better predict the natural history of the disease and its sensitivity to treatment. A large-scale molecular characterization of breast cancer could help in this context. Using cDNA arrays, we studied the quantitative mRNA expression levels of 176 candidate genes in 34 primary breast carcinomas along three directions: comparison of tumor samples, correlations of molecular data with conventional histoclinical prognostic features and gene correlations. The study evidenced extensive heterogeneity of breast tumors at the transcriptional level. A hierarchical clustering algorithm identified two molecularly distinct subgroups of tumors characterized by a different clinical outcome after chemotherapy. This outcome could not have been predicted by the commonly used histoclinical parameters. No correlation was found with the age of patients, tumor size, histological type and grade. However, expression of genes was differential in tumors with lymph node metastasis and according to the estrogen receptor status; ERBB2 expression was strongly correlated with the lymph node status (P < 0.0001) and that of GATA3 with the presence of estrogen receptors (P < 0.001). Thus, our results identified new ways to group tumors according to outcome and new potential targets of carcinogenesis. They show that the systematic use of cDNA array testing holds great promise to improve the classification of breast cancer in terms of prognosis and chemosensitivity and to provide new potential therapeutic targets.

Adult↗

PubMed2000

Local and distant failures after limited surgery with positive margins and radiotherapy for node-negative breast cancer.

PURPOSE: To determine the outcome of patients with positive margins after lumpectomy for breast cancer and to address the issue of the relationship between local recurrences and distant metastasis in the absence of chemotherapy. METHODS AND MATERIALS: Among 3697 patients with primary breast cancer, we retrospectively analyzed 152 patients who had undergone conservative surgery with axillary dissection, had infiltrating carcinomas with positive margins, were node-negative, and received radiotherapy without chemotherapy. One-third received hormonal therapy. Endpoints were local failure and distant metastasis. Median follow-up was 72 months. RESULTS: Five- and 10-year recurrence-free survival were 0.80 and 0.71 respectively for local recurrences, and 0.85 and 0.73 respectively for metastasis. Infiltrating carcinoma on the margins was associated with early local relapse as opposed to intraductal carcinoma. Local and distant recurrences had similar patterns of yearly-event probabilities. Hazard of relapsing from metastasis was 2.5 times higher after a local recurrence. In the multivariate analysis, negative estrogen receptors (ER-)(p = 0.0012), histologic multifocality (p = 0.0028), and no hormonal therapy (p = 0.017) predicted local relapses, while ER- (p = 0.004) and pathologic grade (p = 0.009) predicted metastasis. Hormonal therapy did not prevent early local recurrences. CONCLUSION: In this population, reexcision is advisable for local purposes and because the data support the hypothesis that local and distant recurrences are tightly connected.

Adult↗