Biomedical subjects

S Jelić

Publications and source records attributed to S Jelić.

At least 37 records · Page 2Linked to original sources

PubMed1997

Androgen level variations, clinical response to LHRH agonists and changes in the quality of life subscales in metastatic prostate cancer--speculations about possible role of the monoamine system.

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result of the change in the level of monoamines in CNS under Zoladex.

Acid Phosphatase↗

PubMed1996

Pilot study of enhancement of cisplatin activity by high dose cytarabine in advanced gastric and colorectal (G3/G4) cancer.

The response rate of advanced gastric cancer to cisplatin monotherapy averages 20% and in colorectal cancer no activity of cisplatin monotherapy has been detected in initial studies. Cytarabine is ineffective in gastric cancer and displays borderline activity in colorectal cancer. In vitro studies on cell lines from human digestive cancers have demonstrated a dose and timing dependent enhancing effect of cytarabine on cisplatin antitumor activity. The aim of the present study was to investigate whether this enhancing activity can also be demonstrated in vivo. We have treated 37 patients with advanced gastrointestinal cancer (21 gastric and 16 colorectal), poorly differentiated G3-G4. The treatment included-Day 1: cytarabine 500 mg/m2 0 h and 12 h, cisplatin 15 mg/m2 6 h and 18 h. Day 2-4:cisplatin 30 mg/m2. Cycles were repeated every 4 weeks. Thirty four patients were evaluable for objective response. The overall response rate was 16.7% (CR 2/18, PR 1/18, SD 5/18, PD 10/18) for patients with gastric cancer and 25% (CR 1/16, PR 3/16, SD 7/16, PD 5/16) for patients with colorectal cancer. Grade 4 anemia (WHO criteria) occurred in 1/37 and thrombocytopenia in 1/37 patients. These patients had previous adjuvant chemotherapy. Vomiting grade 3 occurred in 4/37 and hepatotoxicity grade 3 in 1/37 patients. There were no toxic deaths. Our study did not demonstrate any enhancement of cisplatin activity by high dose cytarabine in advanced gastric cancer. There appears to be an enhancing activity on colorectal cancer although true synergism can not be ruled out since cytarabine has a borderline activity in this type of human cancer.

Aged↗

PubMed1996

[A pilot study of high-dose zorubicin in advanced stages of soft tissue sarcoma in adults].

High-dose anthracyclines, doxorubicin 75 mg/m2 and epirubicin 150-180 mg/m2, are the most active drugs in the treatment of advanced soft tissue sarcoma. These dosages are associated with significant hematological toxicity for both drugs and a high risk of cardiotoxicity for doxorubicin. The aim of this pilot study was to investigate the activity of zorubicin in advanced soft tissue sarcoma, with a dosage supposed to be equihematotoxic to epirubicin 180 mg/m2. Twenty of 21 patients who had been included in the study were evaluable for response, 15 males and five females, median age 41 (range 20-67) years. All patients received zorubicin 600 mg/m2 per cycle divided in 3 days, the intercycle interval being 4 weeks. The cardiac function was monitored by determinations of left ventricular ejection fraction before each cycle. Therapeutic response was the following: 2/20 patients (10%) complete response, 6/20 (30%) partial response, 6/20 (30%) stable disease and 6/20 (30%) progressive disease, the overall response rate being 8/20 (40%). Complete responses were observed in a patient with undifferentiated sarcoma of the mediastinum and in a patient with unresectable angiosarcoma of subcutaneous tissues. The major toxicity was hematological, with granulocytopenia grade 4 occurring in 42/66 cycles, and the nadir on day 10 of the treatment cycle. Nine of 66 cycles were complicated by febrile neutropenia and stomatitis of any grade was recorded in only 1/66 cycles. No cumulative cardiotoxicity was observed up to a total cumulative zorubicin dose of 3,000 mg/m2.

Adult↗

PubMed1995

Cardioprotection with ICRF-187 (Cardioxane) in patients with advanced breast cancer having cardiac risk factors for doxorubicin cardiotoxicity, treated with the FDC regimen.

A study of cardioprotection with ICRF-187 (Cardioxane, Eurocetus) has been performed in 35 patients with metastatic breast cancer treated with the FDC regimen (5-fluorouracil 500 mg/m2 i.v., day 1; doxorubicin 50 mg/m2 i.v., day 1; cyclophosphamide 500 mg/m2 i.v., day 1). All patients had one or more cardiac risk factors for doxorubicin cardiotoxicity including 24 who had previously received left-chest-wall irradiation. Cardioxane was applied at a dosage of 1000 mg/m2 as a 15-min infusion in Ringer lactate solution 30 min before doxorubicin administration. Cardiological monitoring included left-ventricular ejection fraction (LVEF) determination by echocardiography before treatment and before each cycle following the cumulative doxorubicin dose of 200 mg/m2. Of the 35 patients, 34 were evaluable fore response, and the overall response rate was 19/34 (56%) with 3/34 complete responses and 16/34 partial responses. Statistical analysis of LVEF values in relation to increasing cumulative doxorubicin doses with Wilcoxon's test of equivalent pairs and Friedman's test has demonstrated that no cardiotoxicity was detected up to a cumulative doxorubicin dose of between 800 mg/m2 and 1000 mg/m2, except for 2 patients in whom a decrease of 20% in relation to the LVEF pretreatment level was demonstrated following a cumulative drug dose of 250 mg/m2. Thus Cardioxane provides an effective cardioprotection even in breast cancer patients with cardiac risk factors for doxorubicin cardiotoxicity treated with the FDC regimen.

Adult↗

PubMed1995

Salivary immunoglobulins in cancer patients with chemotherapy-related oral mucosa damage.

In 40 patients with neoplastic disorders treated with chemotherapy containing anthracyclines or 5-fluorouracil, objective changes of the oral mucosa were registered in 22 patients (55%). Serum IgG and IgA levels and the mean serum IgG/IgA ratio were normal. On the contrary, the mean IgG/IgA salivary ratio was 1.27 (normally below 1.0) due to an increased salivary concentration of IgG (mean 0.095 g/l), but also due to a decreased IgA concentration (mean 0.075 g/l); the IgG/IgA ratio in saliva was higher in patients with objective changes of the oral mucosa (1.53). Values of the periodontal indices were compatible with the diagnosis of a manifest periodontal disease, which tended to be more severe than in control groups. A positive correlation between the gingival index and concentration of IgG in saliva, a non-linear correlation between the gingival index and salivary IgA and a positive linear correlation between serum IgA concentration and intensity of periodontal attachment level recession, indicate local and systemic immune responses to periodontal tissue alterations and dental plaque components. The IgA related local humoral immune response is, however, operating at a lower concentration level than in healthy individuals.

Adult↗

PubMed1995

Reactivity of monoclonal antibodies OK-CLL (anti-CD5) with peripheral blood cells of patients with B cell lymphoproliferative disorders.

Reactivity of OK-CLL monoclonal antibodies that can identify CD5 antigen on peripheral blood mononuclear cells, was investigated in 172 patients with B cell chronic lymphocytic leukemia (B-CLL) in clinical stages RAI O-I and RAI II-IV and in patients with non-Hodgkin's lymphomas, classified according to the Working formulation into high and low grade histologic type. The OK-CLL reactivity with B-CLLs in the initial (RAI O-I), as well as in advanced stages of disease (RAI II-IV) was significantly higher than in controls. Peripheral blood cells of lymphoma patients, regardless of histological type, showed a much lower values of the CD5 positive population than chronic lymphocytic leukemia (CLL) patients, and a non significant discrepancy between the number of cells stained with anti-CD5 and those stained with other T cell markers. In spite of the showed considerable decrease of CD5 positive cells in CLL patients during therapy, elevated number of this population compared to normal individuals, after chemotherapy, was found. However, in lymphoma patients of both types of malignancies, CD5 positive population increased concomitantly with therapy. These results may suggest that analysis of CD5 antigen expression on peripheral blood cells of patients with B cell lymphoproliferative malignancies may have diagnostic, or, in correlation with some relevant clinical parameters, a potential predictive value in the treatment of those patients.

Adult↗

PubMed1994

A pilot study to assess the efficacy of salmon calcitonin in the relief of neuropathic pain caused by extraskeletal metastases.

Although the pain-relieving activity of salmon calcitonin has been mainly demonstrated for painful bone metastases it has been postulated that the drug possesses a central analgesic activity which is independent of the opiate receptor system. Thus, 16 patients with neuropathic cancer pain due to radicular compression by extraskeletal metastases, and without the possibility of any specific anticancer treatment, entered the study. Of the 16, 11 were pretreated with opiate-type analgesics. Salmon calcitonin was applied once daily at a dose of 200 IU in 500 ml 0.9% NaCl infused over 1 h. The total duration of the treatment was 20 days. The pain-relieving effect was classified as very good, good, moderate and bad; in 10 patients it was described as bad, in 2 as moderate in 2 as good and in 2 as very good. The drug failed in 9/11 opiate-pretreated patients. It is suggested that salmon calcitonin pain-relieving activity might depend on the tumor type, previous pain-relieving drug intake and site of metastatic disease.

Administration, Intranasal↗

PubMed1994

[Effect of interferon alpha on immunologic parameters in patients with carcinoma of the renal parenchyma].

A wide range of immunological abnormalities have been described in renal-cell carcinoma (RCC). The only constant one was the decrease of CD4/CD8 ratio, reversible following radical nephrectomy in the absence of metastases. Alpha-interferon was administered with variable benefit to patients with metastatic RCC. The aim of this study was to document whether the treatment of patients with metastatic RCC, with unpurified human alpha-interferon, induced any change in the number and functional properties of peripheral blood T lymphocytes and monocytes. Fifteen patients were included in the study; all were treated with IFN 2,000,000 IJ/24h x 15 days, with an intercycle interval of 15 days during at least 4 cycles. The immunological analyses included the percentage and absolute number of E-rosette forming cells, CD3+, CD4+, CD8+ and CD4/CD8 ratio as well as the percentage and absolute number of monocytes and their phagocytic index toward the yeast particles. The analyses were done before the treatment and after the 4th cycle of the IFN therapy and compared toward the same analyses done in 22 healthy controls. Following IFN treatment two significant changes were noted: a decrease in CD4/CD8 ratio (mean 1.050 fall for 19% to 44%, mean 27.25% from the initial value) as well as a marked decrease in monocyte phagocytic index (p < 0.005). These data point to either disease-related or treatment-related decrease in the phagocytic properties of monocytes and the decrease of CD4/CD8 ratio.

CD4-CD8 Ratio↗

PubMed1994

[The effect of interferon alfa-2b therapy on titers of isohemagglutinins and anti-Forssman antibodies in patients with malignant melanoma].

According to experimental data, administration of interferon in mice before contact with antigen reduced antibody response, while its presence after antigen load enhanced them. The aim of this study was to detect possible immunomodulatory effects of unpurified human alpha-interferon on izohemagglutinin (IZO), and anti-Forssman antibody (AFA) serum levels during a treatment in patients with malignant melanoma. Fifty-two patients treated with the same chemotherapy regimen (ADM-VCR-CPM-DTIC-PCB) entered the study; 30 received INF 1.000.000 U/24 h x 10 during each cycle, intercycle interval 4 weeks. Twenty-two did not receive interferon. Initial IZO titers were 1/4-1/256, median 1/64, and for AFA 0-1/14, median 1/7. Following 4 cycles, values for IZO titers were: in the IFN group 1/32-1/262.144, median 1/128; in the non-IFN group range 1/8-1/512, median 1/32. The values for AFA titers were: in the INF group 0-1/442, median between 1/28 and 1/56; in control group 0-1/112, median 1/14. The difference between both median values for the INF group and initial median values was statistically significant. Initial elevation of titers was reversed during a few cycles with both A and B substances and the Forssman antigen, immunisation of humans is permanent. It would be of interest to ascertain effects of interferons on antibody response to others antigens, especially bacterial and viral, during aggressive chemotherapy. In any case, both experimentally observed phenomena seem to occur in vivo during interferon treatment of metastatic melanoma.

Antibodies↗

PubMed1994

[Therapeutic possibilities of recombinant interferon alfa-2b (Intron A) in non-AIDS Kaposi sarcomas and angiosarcomas].

Data concerning treatment of vascular neoplasia with biological response modifiers are still scanty, but encouraging results have been observed with alpha-2b interferon in AIDS related Kaposi sarcoma. In this study five treatment naive patients with Kaposi sarcoma and four heavily pretreated patients with angiosarcoma with still evolutive disease were treated with Etopozid 120 mg/m2/24h, days 1, 3 and 5, and recombinant alpha-2b interferon 6.000.000 U/24h, days 1-15, the intercycle interval being 21-28 days. All patients were negative for anti-HIV 1, anti-HIV 2 and anti-HTLV 1 antibodies; one patient had a high titer of IgG anti-chlamydia antibodies amounting to 1/4.194.304. This group differed from similar HIV 1 positive patients by having a normal CD4/CD8 ratio. In the Kaposi sarcoma group 1/5 achieved a complete response lasting 24+ months and 3/5 achieved a good partial response lasting 5+, 12+ and 35+ months. In the angiosarcoma group 1/4 patient achieved a complete response but relapsed after 18 months and one patient experienced stable disease lasting for 15+ months. These findings could be understood in two different ways. Since an infective etiology has been proposed for Kaposi sarcoma, the positive effect of alpha-2b interferon could be related to its "antiinfective" effects observed in viral disorders. However, similar activity in angiosarcoma points to the possibility that the positive effect of alpha-2b interferon in this group of disorders is related to interfering effects of the drug with factors implicated in neoplastic angiogenesis.

Adult↗

PubMed1994

Non-IPSID small intestinal lymphoma: evidence for disseminated disease at presentation.

During the period 1984-1989 the authors have observed 20 patients with non-IPSID small intestinal lymphomas, 11 males and 9 females. In 11 patients the first symptoms were abdominal cramps requiring laparotomy, in 4 ileus, and in 5 perforation with peritonitis. Resection of the involved part of the intestine was performed in 17 patients. Lymphoma tissue was present in 4 of 5 retrogradely examined resection lines on macroscopically normal small intestine. According to Working Formulation, 3 patients had low grade, 3 intermediate grade and 14 high grade histology. Affection of extra intestinal/mesenteric structures was found in 18 of 20 patients, with a total of 36 other lymphoma localizations. 8 of 20 had affection of the nasopharynx and/or Waldeyer's ring. According to the Crowther's classification 55% of patients were in Stage IV, 35% in Stage III and 10% in Stage Ib. All patients were treated with chemotherapy, 13 with ProMACE regimen and 7 with CHOP-type regimens. Ten of twenty patients are alive and in complete remission for over 5 years (7 of 11 of Stage IV and 3 of 9 of Stage Ib/III; 8 of 14 with high grade and 2 of 6 with intermediate/low grade histology). Our results point to the fact that in non-IPSID lymphoma of the small intestine, lymphoma involvement of the intestinal wall might be present beyond obvious lymphoma lesions. Most patients with apparently primary small intestinal lymphoma have a widespread disease. Thus, local forms of treatment such as surgery, and/or radiotherapy can not be expected to be curative in the majority of patients. Data from this study suggest that following initial surgery the chemotherapy is the treatment of choice for these patients.

Adult↗

PubMed1990

High-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A chemotherapy regimen with epirubicin (60 mg/m2, days 1, 2 and 3) and cisplatin (30 mg/m2, days 2, 3, 4 and 5) was started for 35 patients with advanced soft tissue sarcoma (28 males and 7 females; median age, 50 years). All patients were chemotherapy-naive and with an expected survival of more than 2 months. All patients were evaluable for activity and toxicity. The intercycle interval was 4 weeks. Median number of cycles applied was 4 (range, 2-8). The overall response rate was 20/35 (57.1%). A complete response (CR) was achieved in 7/35 patients (20%), lasting for 26+, 26+, 13+, 13+, 9+, 9+ and 5 months; 13/35 patients (37.1%) entered a partial remission (PR), 9/35 patients (25.7%) had stable disease (SD), and 6/35 (17.1%) had progressive disease (PD). In non-responders (SD + PD), the median survival was 4 months; the median survival of responders (CR + PR) was 9+ months (the median has not yet been reached). Hematologic toxicity of grade 4 was present at least in one cycle for hemoglobin in 6/35 patients, for leukocytes in 22/35, and for platelets in 13/35. No hemorrhagic syndrome was observed. The leukopenia was usually of short duration (nadir on days 10-12). Febrile episodes were present in 18 patients during the nadir of leukopenia. No other significant toxicity was noted (apart from grade III alopecia in all patients), and specifically, there was neither acute nor cumulative cardiotoxicity.

Adult↗

PubMed1988

EDTA clearance in monitoring cisplatin dose escalation in patients with bulky metastatic germ cell tumors of the testis.

A fast cisplatin clearance may reduce exposure time of tumor cells to the drug, and thus impair the expected effects of dose escalation. This hypothesis was tested in 23 patients with bulky metastatic germ cell tumors of the testis, treated with etoposide, bleomycin and high-dose cisplatin (60 mg/m2/24 h x 4). The daily dose was retrospectively calculated in mg/l EDTA clearance/24 h. A daily dose of 60 mg/m2 of cisplatin in a person with a body surface of 1.7 m2 and EDTA clearance of 100 ml/min was equivalent to 0.69 mg cisplatin/l EDTA clearance/24 h. In the whole group, 10 patients had complete remission (CR), 10 partial response (PR) and 3 progressive disease (PD). The mean daily cisplatin dose (mean) in the whole group was 0.86 mg/l EDTA clearance/24 h (range 0.35-2.00). For patients with CR, mean +/- SD was 1.00 +/- 0.46, for those with PR 0.80 +/- 0.44, and for those with PD only 0.61 +/- 0.07. A cisplatin dose over 0.86 mg/l EDTA clearance/24 h x 4 was obtained in 6/10 patients with CR versus 2/13 patients with PR + PD. Patients with PD received a significantly lower cisplatin dose than the whole group (0.61 versus 0.86 mg cisplatin/l EDTA clearance/24 h x 4.) The difference between the average toxicity grade after cisplatin dose over and below 0.69 mg/l EDTA clearance/24 h x 4 was significant only for leukocytes (WHO grade 2.17 versus 1.36). Thus, the effective escalated dose of cisplatin should preferably be calculated not per m2 body surface but per 1 liter EDTA clearance. The 'ideal' escalated dose might be about 0.86-1.0 mg cisplatin/l EDTA clearance 24 h x 4.

Cisplatin↗

PubMed1987