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L Mitrović

Publications and source records attributed to L Mitrović.

15 recordsLinked to original sources
PubMed2001

Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.

This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving cisplatin 120 mg/m(2), mitomycin C 8 mg/m(2) and vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving carboplatin 500 mg/m(2) with the same doses of mitomycin C and vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and tumor histological grade (I+II vs. III). In the cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the carboplatin arm. The advantage for patients receiving carboplatin instead of cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the carboplatin than in the cisplatin arm (P=0.012). Thus, substitution of cisplatin by carboplatin in the combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.

Adult↗
PubMed2001

Tumor 'flare' hypercalcemia--an additional indication for bisphosphonates?

The most serious, potentially life-threatening manifestation of 'flare' is hypercalcemia, registered in 4-5% of breast cancer patients with bone metastases, usually during the first few weeks of tamoxifen treatment. There are no specific treatment recommendations for flare hypercalcemia, except tamoxifen withdrawal. There are no reports on the use of bisphosphonates in the treatment of flare hypercalcemia. Among 87 hypercalcemic patients with metastatic breast cancer observed during a 7-year period, 10 patients had tamoxifen-induced hypercalcemia. Diagnosis of flare hypercalcemia was based on the normal pretreatment values of serum calcium and the development of hypercalcemia within a maximum of 6 weeks of hormonal drug initiation. The median time from hormonal drug initiation to flare hypercalcemia was 14 days, the median duration 8.5 days, and the median calcium level was 3.09 mmol/l (range 2.79-4.46 mmol/l). All patients were treated with hydration, and 7 patients with calcium levels above 3.0 mmol/l were also treated with disodium pamidronate in various single doses (30-90 mg/24 h). Normocalcemia was achieved in all patients, and tamoxifen was continued without relapse of hypercalcemia. Median survival was 177 days (range 12-570 days). It seems that the use of bisphosphonates in the treatment of flare hypercalcemia could allow safe readministration of tamoxifen and prevent premature and unjustified tamoxifen discontinuation. Flare hypercalcemia might represent one more indication for the use of bisphosphonates.

Adult↗
PubMed2000

Patient statement of satisfaction with antiemetic treatment is related to quality of life.

The aim of our study was to explore the possible relationship between patient satisfaction with antiemetic treatment and quality of life (QoL). The study sample consisted of 136 chemotherapy-naive patients with breast cancer, with Karnofsky index 90% to 100%, scheduled to receive their first cycle of, mainly adjuvant, 5-fluorouracil/doxorubicin/cyclophosphamide chemotherapy. Two antiemetic regimens were used for the prevention of acute emesis. No antiemetic prophylaxis was given for delayed emesis. QoL was assessed using the Rotterdam Symptom Checklist (RSCL). The RSCL was completed before chemotherapy (day 1) and on day 5. Statement of satisfaction was given on day 5. The change in RSCL scores between day 5 and day 1 was calculated and compared in three subgroups of patients: those very satisfied (n = 55), satisfied (n = 65), and unsatisfied with antiemetic treatment (n = 16). Patient statement of satisfaction was related to psychological distress (p = 0.002), physical symptom distress (p = 0.002), and activity level (p = 0.002). It was also related to the control of nausea (p < 0.01) and vomiting (p < 0.0001). We suggest that patient statement of satisfaction with antiemetic treatment could be an outcome measure for response assessment in antiemetic trials.

Adult↗
PubMed1999

Expression of epidermal growth factor receptor in breast cancer, from early stages to advanced disease.

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.

Aged↗
PubMed1998

Cathepsin D: association between TN-stage and steroid receptor status of breast carcinoma.

PURPOSE: To assess whether the expression of estrogen-induced protease, cathepsin D, might facilitate biological subgrouping of patients with breast carcinomas, and accordingly, its potential applicability in clinical oncology. PATIENTS AND METHODS: This study includes 70 patients with histologically confirmed breast carcinoma. Pathological findings were classified according to tumor size (T) and the presence or absence of metastases in regional lymph nodes (N). Steroid hormone receptor (SR) density as well as cathepsin D concentrations were assayed in the cytosol of breast carcinomas in accordance with the recommendation of the EORTC. RESULTS AND DISCUSSION: Statistically significant direct correlations were observed between cathepsin D expression and axillary node status as well as SR status. However, it is important to point out that in spite of these statistically significant findings, there were no biologically significant associations due to a wide range of individual cathepsin D values. Baseline levels of cathepsin D expression were found in patients with SR-negative status and node-negative tumors as well as in patients with SR-negative status and tumors of </=2 cm. Accordingly, a clinical significance of cathepsin D expression may be assumed.

Biomarkers, Tumor↗
PubMed1998

Evaluation of the nutritional status and tumor characteristics in premenopausal and postmenopausal breast cancer patients.

Evaluation of the nutritional status, fat tissue distribution, and tumor characteristics was carried out in patients with primary breast cancer. The patients were classified into two groups according to their menopause: premenopausal and postmenopausal. Breast cancer prevalence was considerably higher in postmenopausal patients (61%). The patients' nutritional status was shown through the body mass index. Based on this indicator, the patients were characterized as nonobese and obese. In the premenopausal group, there was no significant difference between these categories, whereas the number of obese patients was significantly higher (80%) in the postmenopausal group. The analysis of tumor parameters as related to menopause and body size did not yield any significant differences. However, the estrogen receptor content was significantly higher in postmenopausal patients (p < 0.0001). Distribution of fat tissue of the android type was higher in obese postmenopausal women than in premenopausal ones (77%). The investigation showed that the breast cancer incidence odds are 3.5 times higher in obese postmenopausal than in premenopausal patients.

Adult↗
PubMed1997

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.

Adolescent↗
PubMed1995

Treatment of tumour-induced hypercalcaemia in advanced breast cancer patients with three different doses of disodium pamidronate adapted to the initial level of calcaemia.

A group of 38 female patients with advanced breast cancer experiencing the first occurrence of tumour-induced hypercalcaemia (TIH), mostly with osteolytic progressive bone metastases, were included in a prospective calcaemia-adapted study using three different doses of pamidronate (30 mg, 45 mg and 60 mg). Serum calcium normalisation was achieved in 29/38 (76%) patients. Comparison of the response rate in three therapeutic groups confirmed the need for higher doses of pamidronate in moderate TIH. Our study also emphasised the importance of effective anticancer systemic therapy.

Adult↗
PubMedDate not supplied

pS2 in breast carcinoma: association with steroid hormone receptor status.

AIMS AND BACKGROUND: Knowledge of the steroid hormone receptors has proved to be of significant value in breast cancer. In the present study the possible importance of estrogen-regulated pS2 protein was investigated. Our direct purpose was to answer the question whether the expression of pS2 may be a marker of functional heterogeneity with respect to the steroid hormone receptor status. METHODS AND STUDY DESIGN: The study included 152 patients with primary, operable, histologically confirmed breast carcinomas. Histology specimens were reviewed and classified according to type, nodal status, tumor size and grade. Steroid hormone receptors were assayed by biochemical methods according to the procedures recommended by the EORTC. pS2 protein measurement was performed in breast carcinoma cytosols using an immunoradiometric assay. The results were analyzed by non-parametric statistical methods. RESULTS: A statistically significant inverse correlation between pS2 protein expression and histological tumor grade was found. The expression of pS2 protein was confirmed to be correlated with steroid hormone receptor status. However, it is important to point out that in spite of these statistically significant findings there were no significant biological associations due to overlapping individual pS2 protein values. The baseline level of expression of pS2 protein was obtained in histological grade III carcinomas with a negative steroid hormone receptor status. It was shown that the distribution of carcinomas according to the baseline level of pS2 protein expression was heterogeneous among estrogen receptor-positive carcinomas, and strikingly homogeneous among estrogen and progesterone-negative carcinoma. CONCLUSION: Our study suggested that PR and pS2 protein may identify distinct subsets of estrogen receptor-positive breast carcinomas.

Breast Neoplasms↗
PubMedDate not supplied

[Malignant mesothelioma--therapeutic response to various combinations of anthracyclines].

This report deals with results of chemotherapy with different antracycline combination in advanced malignant mesothelioma. Two patients were treated with CYVADIC combination including Adriamycin 40 mg/m2. There was no treatment response and both patients were evaluated as stable disease with median survival 5.5 months and median time to progression 4 months. Four patients were treated with Adriamycin 75 mg/m2 and Cisplatin 120 mg/m2. Two patients achieved a partial response with median survival 8 months and median time to progression 6.5 months. Combination treatment with Epirubicin 180 mg/m2 and Cisplatin 120 mg/m2 was applied to 5 patients, 4 being evaluable for activity. There was one partial response, median survival in this group was 5 months and median time to progression 3.5 months. The Adriamycin dose of 75 mg/m2 and the Epirubicin dose of 180 mg/m2, which were used in our patients are the highest escalated doses, not reported in literature data. Using the meta-analysis of both literature data and our study, which can be considered as a pilot study for dose escalation, there seems to be dose-effect relationship for antracyclin activity in malignant mesothelioma. The meta-analysis registers also slightly better treatment results (response rate 12.6% in 277 patients) with antracyclin containing regimens as compared to combination chemotherapy which does not include antracyclines (response rate 10.3% in 175 patients).

Antibiotics, Antineoplastic↗