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P Viens

Publications and source records attributed to P Viens.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Why use chemotherapy in cancer of the bladder? What are the initial limitations].

Four chemical agents are active, in isolation, against metastatic bladder cancer: cisplatin (nephrotoxicity) (C or Cis), doxorubicin (cardiac toxicity) or adriamycin (A), vinblastine (V) and methotrexate (M). Combinations of these drugs are more effective, with complete response rates of up to 30 to 40%. The current combinations are: CM; Cis cyclophosphamide, A; CMV; MVAC. This last combination appears to be the most effective. Chemotherapy is essentially prescribed for palliative purposes (improvement of symptoms) in metastatic cancers. It may also constitute adjuvant treatment following total cystectomy, in order to decrease the local or distant recurrence rate. Neoadjuvant chemotherapy, before surgery, can reduce the tumour bulk allowing preservation of the bladder. Haematopoietic growth factors are used to reduce the toxicity of chemotherapy and the action of these drugs can also be potentiated by radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Detection of circulating antigens in the diagnosis of acute toxoplasmosis.

Using an enzyme-linked immunosorbent assay, we have found circulating antigens of Toxoplasma gondii in three models of murine toxoplasmosis: mice infected with trophozoites of the RH strain (acute toxoplasmosis), the Beverley strain (subacute toxoplasmosis), and the T626 strain (chronic toxoplasmosis). Circulating antigens were detected 48 hr after infection in the mice infected with the RH strain, and all mice had antigenemia by the fourth day. In those infected with the Beverley strain, circulating antigens were detected from the second day after inoculation until the end of the study, with a peak (71% of the infected mice) on day 10. Of those infected with the T626 strain, 40% had antigenemia at 13 days after infection. The detection of circulating antigens in serum is directly related to the presence of toxoplasmosis in the acute phase in the three models studied and, therefore, may prove very useful in the rapid diagnosis of this disease.

Acute Disease↗
PubMed1994

Bone marrow transplantation in 63 adult patients with acute lymphoblastic leukemia in first complete remission.

Over a 10 year period, we transplanted 63 patients with acute lymphoblastic leukaemia (ALL) who had achieved first complete remission (CR). All were > 15 years old and 45 (71%) had at least one poor prognostic factor. Twenty-nine patients with a suitable sibling underwent autologous bone marrow transplantation (BMT). Beginning in 1984, patients without a donor received an allogeneic BMT (34 patients). Preparation consisted of cyclophosphamide (CY)/TBI (78%) or melphalan (Mel)/TBI (22%); marrow was treated in vitro in 31 patients (allogeneic: 7; autologous: 24). Kaplan-Meier estimates of the probability at 6 years of relapse, survival and DFS were 41% (allogeneic: 10%, autologous: 65%, p < 0.05), 44% (allogeneic: 62%, autologous: 26%, p = NS) and 42% (allogeneic: 62%, autologous: 27%, p < 0.06), respectively. This report confirms that allogeneic BMT permits long-term remissions giving high levels of survival when performed shortly after entering first CR while autologous BMT, when performed in the same setting, is less successful at preventing relapse. This study also confirms the high sensitivity of ALL to the graft-versus-leukemia effect provided by allogeneic BMT. Chemoradiotherapy dose intensification delivered at autologous BMT is not sufficient to prevent relapses. Autologous BMT must therefore be augmented by other approaches of which immunotherapy may be one.

Adolescent↗
PubMed1993

[Hematopoietic growth factors].

Haematopoietic growth factors are a family of genetically determined low molecular weight glycoproteins which regulate the proliferation and differentiation of haemopoietic cells through specific membrane receptors. GCSF and GMCSF reduce the morbidity from infections associated with the neutropenia induced by chemotherapy of onco-haematological neoplasia; EPQ totally corrects not only the anaemia of patients with chronic renal failure, but also 50 percent of anaemias related to chemotherapy; finally, the activity of IL 3 on platelet production seems to control the thrombocytopenia which restricts the use of therapeutics.

Erythropoietin↗
PubMed1993

High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of carboplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study.

25 patients with poor-prognosis malignancies were treated with a combination of fixed-dose etoposide (1750 mg/m2), cyclophosphamide (6400 mg/m2) and escalating doses of carboplatin (from 800 to 1600 mg/m2) followed by autologous bone marrow transplantation (ABMT). The median duration of granulocytopenia (< 500/mm3) and thrombocytopenia (< 20,000/mm3) was 23 days and 20.5 days, respectively. The main non-haematological toxicity was gastro-intestinal, with moderate to severe diarrhoea in 15 patients. No significant renal toxicity was observed. 2 patients died early due to toxicity. The overall response rate was 58% including 42% having complete responses. 4 of the 25 patients are alive with no evidence of disease at 22, 27, 40 and 43 months after ABMT. The encouraging antitumoral activity of this regimen makes it a good candidate for intensified chemotherapy in patients with various malignancies. Toxicity is acceptable and may be reduced in the near future with the widespread use of haematopoietic growth factors.

Adolescent↗
PubMed1993

Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies.

Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Simultaneous radiotherapy and chemotherapy in the treatment of advanced cancer of the cervix uteri].

The pelvis is a major site of failure in patients with advanced carcinoma of the cervix. Attempting to improve local disease control, 40 patients were treated between February 1988 and July 1992 with concurrent chemoradiation (CCR). Thirty three patients (group A) with bulky cervical tumors (> 5 cm) received this CCR as the first part of their treatment (stages IB: 4; IIB with distal parametrial involvement: 14; IV: 15). CCR was followed by brachytherapy and a parametrial boost if indicated, then by surgery. CCR was also given, as a postoperative treatment, in seven patients (group B) with a bulky nodal involvement on a previous hysterectomy with lymphadenectomy performed for an early stage. CCR was a pelvic radiation therapy (RT): 45 Gy/25 F/33 d (two fractions per day in the last 14 patients) and a chemotherapy delivering: CDDP 60 mg/m2 on days 1 and 21, followed by 5-FU 600 mg/m2 i.v. continuous infusion for 96 hours (respectively 40 and 400 mg/m2 in the 16 last patients). Median follow-up is 35 months (range 10-63 m). Acute toxicities were grade 3-4 diarrhea in 16 patients and another patient died from a septic episode without leucopenia after CCR. Five post-operative complications required a second surgical procedure. Among these five patients, one died and two other developed small bowel late complications. No post-operative or late complication were observed in patients treated with a bi-fractionated RT. Sites of failure were: pelvic: four; metastases: five, both: three. Thirty months survival and DFS rates were 67.5% and 58.4% in the whole series and respectively 64% and 52.5% in stages IB-IIB patients and 63% and 59% in stage IV patients. Surgery is an important factor of the treatment and a CCR with a bi-fractionated RT allows such a surgical procedure. These encouraging results must be confirmed by a prospective study to determine whether a CCR is able to improve local control and survival.

Adult↗
PubMed1993

[High dose chemotherapy with autologous bone marrow transplantation in ovarian adenocarcinoma].

The present treatment of advanced ovarian adenocarcinoma patients is unsatisfactory, with 5-year survival rates of less than 15%. To obtain better results, one possibility is the use of therapeutic intensification with autologous bone marrow support. In effect, there is a known dose-response relationship in ovarian carcinoma, especially with alkylating agents. To date, a 69% response rate has been achieved with this kind of treatment in 39 patients refractory to standard therapy. However, responses are of short duration, with a median range of 6-7 months. Therapeutic intensification has been used in over 100 patients, as consolidation therapy, following first-line chemotherapy. For these patients, projected 3-year overall survival and disease-free survival rates are 30-50% and 20-40% respectively. These results compare favorably to those of standard therapy. Early deaths are more frequent in refractory patients (18%). Complete hematological recovery usually occurred within 3-4 weeks. Extra-hematological toxicity is related to previous treatment and to cytotoxic drugs used during intensification. These preliminary results, limited to a small series of patients, are sufficiently promising to continue and extend these trials.

Adenocarcinoma↗
PubMed1993

Results of a prospective study with comparison of clinical, endosonographic, computed tomography, magnetic resonance imaging and pathologic staging of advanced gynecologic carcinoma and recurrence.

Between January 1988 and April 1991, 57 patients with advanced gynecologic carcinoma were preoperatively evaluated by gynecologic examination and endosonography (ESG) using general anesthesia. Abdominopelvic computed tomography (CT) was performed in 49 patients and magnetic resonance imaging (MRI) in 21 patients. There were 34 primary tumors and 23 instances of recurrence. Causes of gynecologic carcinoma were 38 carcinomas of the cervix uteri (26 primary and 12 recurrences), eight carcinomas of the ovary (four primary and four recurrences), three recurrences of carcinoma of the endometrium, five sarcomas of the uterus (one primary and four recurrences) and three primary carcinomas of the vagina. All of the patients were operated upon. This perspective study compares the data from clinical and imaging examinations to the data obtained from histologic examination of surgical sections. According to anterior or posterior tumor extension, the accuracy of clinical evaluation and preoperative imaging were studied for the posterior vesical wall and the vesicovaginal septum and the anterior rectal wall and the rectovaginal septum. Histologic examination revealed vesical involvement in 17 patients and of the involvement of vesicovaginal septum in 21 patients. The accuracy of the clinical examination, ESG, cystoscopy, CT and MRI was 83, 88, 87, 75 and 81 percent, respectively, for vesical extension. Cystoscopy was not taken into account for evaluation of extension to the vesicovaginal septum--accuracy was 80, 90, 67 and 86 percent for clinical examination, ESG, CT and MRI. Histologic examination showed involvement in the rectum in 14 patients and involvement in the rectovaginal septum in 19 patients. Rectoscopy was performed 13 times. The accuracy of clinical examination, ESG, CT and MRI was 91, 98, 89 and 71 percent, respectively, for extension to the anterior rectal wall. Rectoscopy was not taken into account for evaluation of extension to the rectovaginal septum--accuracy was 80, 96, 75 and 57 percent for clinical examination, ESG, CT and MRI. Endosonography would seem to be useful to complete examinations for regional extension of advanced gynecologic carcinomas. Its accuracy is superior to that of other examinations. Because it is performed using general anesthesia, there is no discomfort for the patient during this low cost procedure.

Cystoscopy↗
PubMed1992

Pharmacokinetics of mitoxantrone in cancer patients treated by high-dose chemotherapy and autologous bone marrow transplantation.

We have studied the pharmacokinetics of mitoxantrone in cancer patients. Two regimens were used: eight women (10 kinetics) received a 10 min i.v. infusion of 12 mg m-2 of mitoxantrone; seven women (seven kinetics) received high-dose mitoxantrone associated to high-dose alkylating agents and underwent autologous bone marrow transplantation (BMT). High-dose mitoxantrone was administered according to two different protocols. The drug was quantified in plasma with an HPLC assay and pharmacokinetic analysis was performed with the APIS software. Mitoxantrone pharmacokinetics were best described by an open two- (six kinetics) or an open three compartment model (11 kinetics). A large interindivual variability was observed in pharmacokinetic parameters. In the first group of patients, mean +/- s.d. values of clearance, half-life and total distribution volume were 21.41 +/- 14.59 1 h-1, 19.83 +/- 23.95 h, 165.89 +/- 134.75 1 respectively. In the high-dose group, these values were 21.68 +/- 7.30 1 h-1, 50.26 +/- 20.62 h, 413.70 +/- 194.81 1 respectively. Results showed that identification through the open 2-compartment model is certainly related to the small number of late time-points. We therefore think that mitoxantrone pharmacokinetics is generally best described by an open 3-compartment model. Clearance values showed that there was no saturation in mitoxantrone elimination, even at the highest doses. Terminal elimination half-life was probably underestimated because of the lack of late time-points in some kinetics. The half-life is long for patients receiving high-dose mitoxantrone (mean value was 50 h) and it would be hazardous to perform BMT too early after mitoxantrone infusion. Mitoxantrone metabolites were detected in the plasma of five patients receiving high-dose mitoxantrone and in one with hepatic impairment.

Adolescent↗
PubMed1992

Intestinal parasite infection in the Kampuchean refugee population 6 years after resettlement in Canada.

A follow-up prevalence study was done in 1989 of the same Kampuchean refugee population (247 subjects) that had been screened and treated for intestinal parasite infection 6 years earlier. A control group (102 subjects) included Kampuchean refugees who had arrived in Montreal at about the same time. These groups did not differ in age, sex, family size, or number of months spent in refugee camps. Statistically significant prevalence differences were observed in the rescreened group between 1982-1983 (63.7%) and 1989 (21.9%) and between the rescreened group and the control group (39.2%). These differences are largely attributable to the elimination of Ascaris infection and decreases in Giardia and hookworm infections. However, Strongyloides infection decreased only slightly (from 15% to 11%) in the rescreened group, while 12% of the control group was infected. Despite an early screening and treatment program, there remain important health risks in this immigrant population due to long-lived potentially pathogenic parasites.

Adult↗
PubMed1992

Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer.

In this Phase I trial, the feasibility of sequential administration of continuous intravenous recombinant interleukin-2 (rIL-2) at 18 x 10(6) IU/m2/day for 6 days, followed by three daily bolus intravenous recombinant tumor necrosis factor (rTNF) infusions at doses escalating between 10 and 120 micrograms/m2/day, was investigated in 31 patients with metastatic malignancies. Prophylactic use of indomethacin prior to and during rTNF administration was found to significantly reduce toxicity. However, despite prophylactic indomethacin, a maximum tolerated dose of rTNF of 120 micrograms/m2 was reached. The limiting toxicity was hypotension. Predictable flu-like toxicities (i.e., fever/chills, hypotension, gastrointestinal toxicity, edema, malaise) were seen in most patients. These started during the rIL-2 infusion and continued during rTNF administration, particularly in the absence of indomethacin. Hematological, renal, and hepatic toxicities were not dose limiting. These toxicities were all reversible after treatment interruption. Pulmonary toxicity [i.e., anaphylactic-like reactions, bronchospasms, and adult respiratory distress syndrome (ARDS)] was seen in several patients immediately after rTNF infusions, irrespective of the rTNF dose or treatment cycle, and mainly in patients with extensive pulmonary metastases. The combined effect of treatment-related ARDS, lung metastases, and a Guillain-Barré syndrome led to the death of one patient. Two partial responses were seen in this study (i.e., breast and renal cancer). Based on these results, a Phase II trial of rIL-2 followed by rTNF has been initiated in metastatic breast cancer patients.

Adolescent↗
PubMed1992

Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer.

Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.

Adolescent↗
PubMed1991

Influence of mixed chimerism on the results of allogeneic bone marrow transplantation for leukemia.

Serial cytogenetic studies were performed on 60 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total body irradiation (TBI). Forty-three patients were recipients of untreated BMT and 17 were recipients of T-depleted BMT. Donor or host mitoses were identified by examination of sex chromosomes in 54 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Mixed lymphoid chimerism (MLC) was identified in 29 patients and full donor lymphoid chimerism (FDLC) in 29 patients. Complete donor hematopoiesis was recovered in most patients after 12 months, but two T-depleted patients had persistent host cells at 46 and 52 months after the graft. Acute graft-versus-host disease was significantly less frequent in patients with MLC, especially when more than 10% of residual lymphoid cells were detected. The probability of relapse and survival was identical in patients with MLC and FDLC, except in patients with chronic myeloid leukemia where MLC was significantly associated with an increased risk of relapse.

Acute Disease↗
PubMed1991

High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse.

Interleukin-2 (IL-2) is able to induce the regression of metastatic cancers when administered in vivo. IL-2-activated natural killer cells and lymphocytes show, in vitro, activities against leukemic cells. To assess if in vitro observations could have significant clinical relevance, we evaluated the in vivo activity of high-dose recombinant IL-2 (6 to 8 x 10(6) IU/m2/8H intravenous bolus for 5 days) in 10 patients with acute myeloid leukemias (AML) in relapse after chemotherapy (n = 7) or autologous bone marrow transplantation (n = 3). Two patients achieved a complete remission and one had a minimal improvement in his marrow blast cells. Response was observed after one cycle of IL-2 in the two patients achieving a complete remission. These two patients relapsed at 3 and 4 months. These results showing clinical activity of high-dose recombinant IL-2 in AML invite further evaluation of this new form of immunotherapy in other clinical situations, like an adjuvant setting for selected groups of high-risk patients.

Adolescent↗
PubMed1991

Anti-LFA1 monoclonal antibody (25.3) for treatment of steroid-resistant grade III-IV acute graft-versus-host disease.

The in vivo efficacy of 25.3 monoclonal antibody (mAb) directed against human LFA1 molecule was assessed in ten patients with steroid-resistant grade III-IV acute graft-versus-host disease (AGVHD). These patients received non-T-cell-depleted allogeneic bone marrow transplantation for aplastic anemia in two cases and hematologic malignancies in eight cases. Five grafts were fully matched, three were one antigen-mismatched, and two were two antigen-mismatched. Despite GVHD prophylaxis with cyclosporin A and short-term methotrexate, AGVHD occurred after a median of 24 days and clearly progressed under prednisone (median 2 mg/kg), given for a median of 12 days. 25.3 mAb was given at a dosage of 0.1 mg/kg in a 4-h perfusion for five daily doses without any clinical or biological side effects. Thirty percent of the patients experienced a reduction in the overall grading with two complete responses. Partial response in at least one involved organ (mostly skin) occurred in 80% of the patients. However, seven out of the eight responding patients experienced a new episode of AGVHD. This observation, which confirms that inhibiting a functional molecule is as efficient as a cytolytic therapy, offers an alternative strategy to antithymocyte globulin (ATG) and cytotoxic mAb in controlling steroid-resistant GVHD.

Acute Disease↗