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Biomedical subjects

M Fridrik

Publications and source records attributed to M Fridrik.

At least 19 recordsLinked to original sources
PubMed2003

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Adult↗
PubMed2003

Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Clinical value of FDG PET using coincident gamma cameras in staging and restaging of malignant lymphoma--compared with convenitonal diagnostic methods].

UNLABELLED: AIM of the present retrospective study was to validate the clinical value of F-18-FDG PET imaging in lymphoma patients with a dual head camera modified for coincidence detection. Staging before and after oncological treatment was compared with a conservative diagnostic approach. METHODS: 48 patients (28 non-Hodgkin lymphoma, 20 Hodgkin's disease) received FDG-Hybrid-PET scans. Pretherapeutic staging was realized in 28 patients, 9 of them had control studies after they had completed therapy. Totally 29 persons were examined for post-therapeutic restaging. Computed tomography imaging and lymph node sonography was performed in all cases. Results were validated by clinical follow-up, in three cases a recidive was proven by biopsy. RESULTS: CT and ultrasound detected 77 lesions in 28 patients compared with 100 visualized by PET, but this difference in pretherapeutic staging did not reach significance at p > 0.05 by Fisher's t-test. Hybrid-PET obtained a sensitivity of 93%, a specificity of 79%, a positive of 82% and a negative predictive value of 92% for detection of residual disease. The values for CT + US were 87%, 64%, 72% and 88% respectively. CONCLUSION: FDG Hybrid-PET is as or even more accurate than standard morphologic diagnostic methods for prestaging in malignant lymphoma. Additionally, there is a substantial benefit for therapy monitoring of residual disease using coincidence detection PET with a 3/4-inch crystal gamma camera.

Adult↗
PubMed1999

Biochemical modulation of 5-fluorouracil by leucovorin with or without interferon-alpha-2c in patients with advanced colorectal cancer: final results of a randomised phase III study.

5-Fluorouracil (5-FU) remains the mainstay of treatment for advanced colorectal carcinoma, although response rates are generally less than 20%. Improved therapeutic efficacy has been reported using biochemical modulation of 5-FU by leucovorin (LV) or interferon alpha (IFN), the combination of 5-FU/LV frequently considered as standard therapy in metastatic colorectal cancer. In an attempt to enhance the cytotoxicity of 5-FU, a prospective randomised trial was initiated to compare 5-FU/LV with 5-FU/LV plus IFN. Patients were randomised to receive either LV, 100 mg/m2 intravenously (i.v.), followed by 5-FU, 500 mg/m2 as a 1-h i.v. infusion, daily for 4 days, followed by weekly infusions until week 8, or the same regimen of 5-FU/LV plus IFN-alpha-2c, 30 micrograms subcutaneously (s.c.), three times weekly. Cycles were repeated after a 2-week rest period. Among 269 enrolled patients, 219 were available for response and 243 for toxicity. An objective tumour response was observed in 38 of 107 (36%) and 28 of 112 (25%) patients in the treatment arms with and without IFN, respectively (difference not significant). There was no significant difference between the two groups in response duration (median 8.4 versus 12.1 months), time to treatment failure (median 6.5 versus 4.9 months), or overall survival (median 10.0 versus 12.6 months). However, patients in the IFN arm experienced significantly more haematological and gastrointestinal toxicity and more frequent alopecia. In conclusion, the addition of IFN to 5-FU/LV in the schedules and doses used in the study did not provide any clinical benefit over 5-FU/LV alone and cannot be recommended for routine use in the treatment of advanced colorectal cancer.

Adult↗
PubMed1999

Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients. Austrian Breast Cancer Study Group.

The aim of our study was to evaluate if p53 mutations, especially those in the L2/L3 domains of the p53 gene, add prognostic information for node-positive and steroid receptor positive breast cancer patients. Two hundred and five tumour samples from a randomised clinical trial of 596 lymph node- and steroid receptor positive breast cancer patients were included. All patients had been randomly allocated to receive 20 mg of adjuvant tamoxifen (TAM) daily for 2 years or TAM plus one cycle of low-dose, short-term chemotherapy. For detection of p53 mutations we used in vitro amplification by polymerase chain reaction and consecutively performed temperature gradient gel electrophoresis (PCR-TGGE) and direct sequencing. We found p53 mutations in 42/205 (20%) cases: 16/42 (38%) p53 mutations occurred within the L2/L3 domains of the p53 gene, and 26/42 (62%) outside the L2/L3 domains. p53 mutation served as a statistically significant parameter in predicting disease-free survival in univariate (P = 0.02) and multivariate (P = 0.009) analysis. For overall survival, no significant differences were observed. Patients with tumours that had p53 mutations within the L2/L3 domains of the gene showed no significant difference to those with mutations outside the L2/L3 domains for disease-free survival. For overall survival, mutations in the L2/L3 domains showed a marginally significant difference (P = 0.05) in multivariate analysis, but not in univariate analysis (P = 0.13). We conclude that mutation in the L2/L3 domains of the p53 gene is not an independent prognostic indicator of disease outcome for patients suffering from breast cancer with lymph node metastases and positive steroid receptors.

Adult↗
PubMed1999

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Age Factors↗
PubMed1999

Monitoring of remission status by fluorescence in situ hybridisation in chronic myeloid leukaemia patients treated with interferon-alpha.

Interferon-alpha (IFN-alpha) can be considered as treatment of choice for patients with chronic myeloid leukaemia (CML) in chronic phase. With this treatment major cytogenetic responses can be achieved in 30% to 50% of patients. Regular monitoring of cytogenetic response is essential for the therapeutic management of these patients. As conventional cytogenetics is not always successful, especially under IFN-alpha treatment, molecular cytogenetic methods have been established for the examination of interphase nuclei for the presence of the BCR-ABL fusion gene, the molecular counterpart of the Philadelphia chromosome. To demonstrate the value of these new methods we have analysed interphase nuclei from sequentially cultured bone marrow cells from 14 CML patients who were treated with IFN-alpha and whose bone marrow was investigated regularly during therapy. Dual-colour FISH with a breakpoint spanning BCR-YAC and a flanking cosmid from the ABL region was applied. When compared with conventional cytogenetics the results achieved by FISH were favourable. The most evident advantage of FISH analysis is that in case of failure of conventional cytogenetics a reliable determination of the remission status can be done. Together with other recent studies our results illustrate the advantages and limitations of the interphase FISH method for monitoring CML patients.

Adult↗
PubMed1998

Interferon-alpha for the treatment of elderly patients with chronic myeloid leukaemia.

The present retrospective analysis is based on data of 213 patients with chronic myeloid leukaemia (CML). They were treated with interferon (IFN)alpha-2C (Berofor) at daily doses of 3.5 MU subcutaneously (s.c.), alone or in combination with low-dose ara-C or hydroxyurea, according to four consecutive studies of the Austrian CML Study Group. Comparisons were made between 41 patients aged > or = 60 years and 172 younger patients. The elderly patients (median: 64 years; range: 60-73) showed similar pretreatment characteristics compared with the younger group, but included a higher percentage of Sokal Stage three (51 vs 20%). Median observation periods were similar (38 vs 39 months), whereas the duration of IFNalpha treatment was shorter in the elderly group (median 57 vs 42 weeks). The rate of overall haematological responses (73 vs 78%) and complete haematological response (44 vs 54%), was similar in both cohorts. Differences seen in partial (5 vs 12%) and complete cytogenetic response (10 vs 13%), were not statistically significant, but a tendency in favour of the younger cohort had to be noted. Summing up, in elderly patients acceptable rates of haematological and cytogentic response can be expected after treatment with IFNalpha alone or in combination with LD ara-C or HU.

Adolescent↗
PubMed1998

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

Adult↗
PubMed1998

[Therapy studies of the Austrian Breast Cancer Group (ABC)].

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Antineoplastic Agents, Hormonal↗
PubMed1997

Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: results of the Austrian multi-center phase II study.

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNalpha) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m2, following an initial reduction of WBC to less than 20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in 3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNalpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.

Adolescent↗
PubMed1995

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer.

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m2 combined with either epirubicin 40 mg/m2 or mitoxantrone 10 mg/m2. All drugs were given by intravenous push, treatment cycles were repeated at 3-4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade > or = 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.

Adult↗
PubMed1995

Malabsorption associated with a high-grade-malignant non-Hodgkin's lymphoma, alpha-heavy-chain disease and immunoproliferative small intestinal disease.

We report on a 28 year old Turkish woman, who was admitted to our hospital with the symptoms of malabsorption and protein-loosing enteropathy. Histologically, on duodenal biopsy, a lymphoplasmacellular infiltration of the submucosa with partial to subtotal atrophy of the villi was found. An immunoproliferative small intestinal disease (IPSID) was diagnosed. A short remission whilst on a glutenfree diet and tetracycline therapy, was followed by a laparatomy because of ileus in the small intestine. A high-grade-malignant Non-Hodgkin's Lymphome of B-cell type with intracellular production of alpha-Heavy-Chains (AHCD) was diagnosed histologically. Following chemotherapy with CEOP-IMVP-Dexa (Cyclophosphamide, Epidoxorubicin, Vincristine, Prednisolone, Ifosfamide, VP-16, Dexamethason, Methotrexat) the patient is still in complete remission three years after starting the therapy. We discuss here a case of AHCD in IPSID, the differential diagnosis of protein losing enteropathy and malabsorption, and we also present conservative (diet, medical treatment) and operative therapies.

Adult↗
PubMed1989

Vindesine-epirubicin versus vindesine-mitoxantrone in metastatic breast cancer.

UNLABELLED: The present study was designed to assess the toxicity and efficacy of two chemotherapy protocols in patients with metastatic breast cancer. Starting in December 1985, 230 patients were randomized to receive vindesine (V) (3 mg/m2 i.v.) and mitoxantrone (M) (10 mg/m2 i.v.) or V and epirubicin (E) (40 mg/m2 i.v.) every 3 weeks x 3 and every 4 weeks thereafter. Patients were stratified according to site of disease (visceral, bone or soft tissue dominant) and prior therapy. Patient groups were comparable with respect to menopausal status, age, estrogen receptor status and disease-free interval. About two-thirds of the patients presented with visceral recurrence and 30% with bone lesions: only 8% had soft tissue metastases. RESULTS: We observed a significant difference (p = 0.003) in the frequency of alopecia (WHO grade 3-4, 36% vs. 60% favoring regimen VM); gastrointestinal and hematologic side effects and neurotoxicity were mild and similar for both groups. In 182 evaluable patients there was a 26% response rate (CR + PR. UICC criteria) for VM and 35% for VE (not significant). NC was observed in 37% and 43% of patients treated with VM or VE respectively. There was no significant difference between these two groups with regard to time to progression and survival. The median time of follow-up was 8 months and therefore too short to draw definite conclusions. Both regimens were well tolerated and seem to be equally effective, although the response rate for VM and VE was lower than expected.

Adult↗
PubMed1988

Translocation t(8;16) in acute monocytic leukemia.

A report is given of three new cases of acute monocytic leukemia, FAB M5a, with a t(8;16)(p11;p13). Two cases showed a marked erythrophagocytosis, including one with phagocytosis of normoblasts and granulocytes. Phagocytosis was absent in the third case. The t(8;16) was the only abnormality in two cases, whereas one case showed clonal evolution with partial trisomy 1q and a deletion of part of the short arms of chromosomes 1 and 3. Treatment results and survival were poor in all cases. A complete remission was achieved in two patients, which lasted only for 3 and 6 months, respectively. In one of these cases a central nervous system relapse occurred. Survival was short, lasting between 1 and 9 months. One patient succumbed to interstitial pneumonitis, a complication of allogeneic bone marrow transplantation without evidence for relapsing leukemia.

Adult↗