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Biomedical subjects

A Cattan

Publications and source records attributed to A Cattan.

At least 19 recordsLinked to original sources
PubMed1996

Phase I/II trial of autologous activated macrophages in advanced colorectal cancer.

Autologous activated macrophage (AAM) therapy is an adoptive cellular therapy based on ex vivo differentiation and activation of autologous peripheral blood monocytes. This study was undertaken to evaluate the tolerance, efficiency and biological effects of AAMs in chemoresistant progressive colorectal cancers. From January 1993 to May 1995, 15 patients were treated. Mononuclear cells were collected six times by weekly apheresis, cultured for 7 days, and activated with interferon-gamma. AAMs were then separated by elutriation and re-infused intravenously, with a mean total of 7.95 x 10(9) macrophages per patient. Clinical tolerance was good: toxicity consisted only of a World Health Organisation grade 2 fever after 28% of the infusions. Responses were not seen in the 14 evaluable patients, as expected with very bulky tumours: in 11, the tumours continued to progress, but disease was stabilised in 3 patients who experienced progression-free survival for 14, 12 and 12 weeks, respectively.

Aged↗
PubMed1996

A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.

This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.

Adult↗
PubMed1993

Phase II trials of tetrahydropyranyl-adriamycin (Pirarubicin) on renal and colon carcinoma, melanoma, and soft tissue sarcoma.

Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given.

Adult↗
PubMed1993

[Correlations between clinical pharmacodynamics and pharmacokinetics of cisplatin and etoposide].

Currently, the dose of anticancer drugs is adjusted according to patient body surface area, although the best criterion for dose adjustment seems to be the plasma concentration of the drug, since a correlation has been established between plasma concentration and efficacy for several drugs. We report here similar results with etoposide and cisplatinum. The plasma concentration and the area under the curve (AUC) of etoposide and platinum (Pt) were higher in responders compared to non-responders, and etoposide clearance was higher in responders. The etoposide toxicity (assessed by the polymorphonuclear blood count) was higher in responders. There was a good correlation between the Pt concentration and creatininaemia. The AUC for Pt was significantly higher in patients with nausea and vomiting. There was no correlation between the infected dose of either drug and efficacy or toxicity. It is not possible to assign efficacy to either compound since they were injected simultaneously. We conclude that when the plasma etoposide or platinum concentrations are low, tumour response is unlikely.

Carcinoma, Bronchogenic↗
PubMed1993

Efficacy of misoprostol in controlling indomethacin induced fecal blood loss in arthritic patients.

Indomethacin, a nonsteroidal anti-inflammatory drug, may cause gastric mucosal damage as shown by fecal blood loss. A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the effects of 400 mcg b.i.d. misoprostol, a synthetic prostaglandin E1 analog, on intestinal blood loss caused by 50 mg t.i.d. indomethacin. Forty-two arthritic patients, mean age 59 years, received indomethacin for 14 days. Those with baseline blood loss of at least 1.5 ml/day during the first 7 days were randomized to 400 mcg of misoprostol or placebo (days 8 to 14). Fecal blood loss was measured using 51Cr labelled red blood cell technique. Success was defined as a reduction in mean daily blood loss of at least 50% during the treatment period compared to mean daily blood loss during the baseline (pre-treatment) phase. The mean daily blood loss on treatment days 9-15 was not significantly reduced from baseline in either group. These data neither confirm nor deny the effectiveness of misoprostol in reducing fecal blood loss caused by indomethacin. The results may have been confounded by the administration of misoprostol twice daily while indomethacin was administered three times daily. In addition, fecal blood loss as an indicator of gastrointestinal mucosal damage is not a sensitive measure; it is characterized by poor reproducibility and wide fluctuations within individual responses. Inappropriate laboratory techniques may have further reduced the sensitivity and reliability of this procedure.

Arthritis, Rheumatoid↗
PubMed1992

Glutathione S-transferase activity and isoenzyme distribution in ovarian tumour biopsies taken before or after cytotoxic chemotherapy.

A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response rates of these two groups to chemotherapy differ markedly, with patients who have relapsed following initial chemotherapy showing a reduction in response rates to subsequent chemotherapy. Analysis of these data show no statistically significant differences between the glutathione S-transferase activity or isoenzyme distribution in these two groups of patients. Significant differences were observed in the glutathione-S-transferase activities (GST) between tumours and normal ovaries. GST activities in pre-chemotherapy tumours (n = 33, P = 0.01) and post-chemotherapy tumours (n = 20, P = 0.001) where significantly higher than the GST activity in normal ovaries (n = 15). One feature was the expression of the basic isoenzyme which is expressed more in normal ovaries than in tumours. No differences in these parameters were observed in normal peritoneal tissue taken from patients before or after chemotherapy. These data do not support the hypothesis that changes in glutathione S-transferase enzyme activity or isoenzyme expression are major determinants of response to chemotherapy in ovarian tumours.

Adult↗
PubMed1991

Correlation of clinical pharmacokinetic parameters of cisplatin with efficacy and toxicity.

Twenty-two pharmacokinetic studies were carried out in 11 patients receiving cisplatin (20 mg/m2 per d) associated with etoposide (50 mg/m2 per d), as 5-day continuous infusions, every 4 weeks. Blood was withdrawn at 8:30 am from day 1-5. Within 15 min after taking the blood, an aliquot of plasma was filtered for the ultrafilterable platinum (UP) assay. Total platinum (TP) and UP were assayed by flameless atomic absorption. The plasma concentrations and AUC0-120 h of TP were correlated with those of UP (P less than 0.05 to P less than 0.001). TP concentrations increased significantly during the infusion and with each successive course, whereas the increase of plasma concentration of UP during and between courses was not statistically significant. The responders had significantly higher levels of TP (AUC, concentrations) in the first and second courses than the non-responders. No renal toxicity was observed, nevertheless, the AUC0-120 h of TP and UP were positively correlated with the serum creatinine (P less than 0.05). The digestive intolerance (grade 1-3) was significantly correlated with TP concentrations and AUC0-120 h. There was no statistical difference in UP concentrations either between responders and non-responders in any course, nor between toxic and non-toxic courses. Since etoposide was concomitantly administered, we can formulate the conclusion as follows: no "objective" response was observed in the patients with low TP plasma concentrations and AUC0-120 h.

Cisplatin↗
PubMed1990

Pirarubicin in advanced breast cancer: a French cooperative phase II study.

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Adult↗
PubMed1990

Discriminating between protective and enhancing HIV antibodies.

Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Five-day continuous infusion of cisplatin and etoposide in non-small cell lung cancer. A phase II trial.

Cisplatin (CDDP) and etoposide are synergistic in vitro: the aim of this study was to evaluate the efficacy of a continuous infusion (C.I.) of these 2 drugs in inoperable non-small cell lung cancer. Patients were to receive 3 courses of CDDP 20 mg/m2/d in 1 l saline x 5d and etoposide 50 mg/m2/d in 21 saline x 5d--both in C.I.--every 3-4 weeks. Thirty patients have entered the study. Four were inevaluable for response. One patient got complete remission, 15 partial remission, 8 no change and 2 progressive disease. The response rate was 53.3% overall (95% confidence interval: 35-71%), and 61.5% for 26 assessable patients. Toxicity appeared to be acceptable despite 52% transient neutropenia--one patient died during aplasia--and 78% grade 1 to 3 nausea or vomiting. Treatment was stopped in only one case, and modified in 6 others. The high response rate that we observed, supports the idea of potentiation of the antineoplastic effect of CDDP and etoposide by C.I., in non-small cell lung cancer. These results must be confirmed in larger series before definitive conclusions can be drawn.

Adult↗
PubMed1989

Serum levels of CA-50, CA-19.9, CA-125, neuron specific enolase and carcinoembryonic antigen in lung cancer and benign diseases of the lung.

The serum levels of five markers (CA-50, CA-19.9, CA-125, Enolase (NSE) carcinoembryonic antigen (CEA) were studied in 96 lung cancer patients and in 60 patients with benign diseases of the lung: sensitivity was 0.44, 0.41, 0.54, 0.23 and 0.38 respectively; specificity was 0.67, 0.87, 0.47, 0.93 and 0.97 respectively. Serum levels of CA-125 over 20 U/ml were found in 74% of patients with acute pneumonia. A good parallel existed between the clinical evolution of lung cancer and the variations in the serum level of CA-50, CA-19.9 and NSE. Although the pretreatment result was elevated, successive assays of the marker allowed the clinical evolution to be followed. Conflicting results were found with CA-125 and to a lesser extent with CEA. A close correlation existed between the serum levels CA-50 and CA-19.9 in the 2 groups of patients. In the absence of a specific marker for lung cancer, complementary information can be provided by means of a simultaneous determination of CEA, NSE, CA-19.9--or CA-50--and CA-125.

Adolescent↗
PubMed1989

[CA-125 in non-ovarian benign and malignant pathology: study on 380 patients].

CA-125, a serum marker of epithelial ovarian cancer, was studied by a radioimmunometric method: the sensitivity and specificity of the assay was studied in 260 patients with non ovarian carcinomas and 120 patients with non malignant diseases. The ideal threshold value has been discussed. Levels higher than 20 UI/ml (cut-off value) have been found in 53% of cases. Sensitivity falls to 25% if the cut-off value is 65 UI/ml. The serum levels correlated well with the existence of a metastatic disease (P less than 0.001). A second assay allowed to study in 163 cases the correlation between the variations of the serum level and the clinical evolution; a good correlation was found except in case of stable disease. High levels have also been found in patients with benign diseases, most of all in cases of pneumonia and severe liver cirrhosis.

Adolescent↗
PubMed1988

Results of a five-drug combination chemotherapy in non-small cell lung cancer. A phase II trial.

Twenty-six non-small lung cancer patients entered a phase II trial of a 5-drug combination chemotherapy. On day 1, patients received vinblastine, bleomycin, methotrexate, 5-FU, cisplantinum, leucovorin, and a similar sequence with an increased dosage was administered on day 6. Out of 22 fully evaluable patients we observed 1 CR and 7 PR. Hematological toxicity was significant, including 15 cases of neutropenia grade 4 and four grade 3, with one death during aplasia. Our results are disappointing but they are similar to most current reports on drug combinations in advanced non-small cell lung cancer. A better scheduling might improve the efficiency toxicity ratio.

Adult↗
PubMed1987

A new approach to image subtraction in immunoscintigraphy: preliminary results.

Recently proposed image comparison software is applied to immunoscintigraphy. The software performs geometric and gray level registration of two images and generates an image of the statistically significant differences. It permits the comparison of scintigraphic images recorded at different times. It is used to subtract 113mIn and 111Inphytate colloid liver scans and early (blood pool) images from 131I or 111In-monoclonal Ab images and to compare Ab images recorded at different times. Using the procedures made possible by this software, only images recorded using the same radionuclide or using radionuclides of about the same energy are compared. Anti CEA, 19-9 and OC 125 F(ab)2 fragments labeled with 131I or 111In are used in 32 patients with 47 demonstrated recurrences or metastases of colorectal or ovarian cancers. The overall sensitivities of the unprocessed and processed images are 25/47 and 41/47 respectively. The improvement in sensitivity is particularly high in the liver when In labelled Ab are used. This technique improves the contrast of the images, but the interpretation must take into account the components of the non target activity (kidney, bone marrow, colon...) which are not removed by the image subtraction method.

Antibodies, Monoclonal↗
PubMed1987

[Comparative analysis of serum levels of CA-50, CA-125, CA-19.9, enolase and CEA in bronchopulmonary cancer].

A serum assay of CA-50, CA-125, CA-19.9, ENOLASE (NSE) and CEA was performed in 65 patients with primary lung cancer, 63% of whom had visceral metastases, with the following histological distribution: squamous carcinoma (40), adenocarcinoma (9), large cell carcinoma (4), oat cell carcinoma (12). A raised CEA level was detected in 37% of cases, compared with 40.6% for CA-50, 44.6% for CA-19.9 and 40.6% for CA-125 and only 26.6% for NSE. Overall, at least one marker was positive in 83% of cases. Statistical analysis of the different markers (correlation analysis and principal component analysis) demonstrated the existence of a strict correlation between the levels of CA-50, CEA and CA-19.9 (p less than 0.01). ENOLASE was more frequently elevated in oat cell carcinomas (42%) than in non-oat cell carcinomas (30%), but the difference was not significant. In contrast, CA-125 appears to be a good marker for non-oat cell carcinomas (51%) (p less than 0.05). The authors also found a correlation between the presence of a raised level of CA-50 (p less than 0.05), CA-125 (p less than 0.02) and especially CEA (p less than 0.001) and the presence of visceral metastases. The initial survey of disseminated lung cancers should include the assay of at least 4 of these markers in order to obtain a reliable serum tracer in more than 2/3 of cases.

Adenocarcinoma↗