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M Untch

Publications and source records attributed to M Untch.

At least 55 records · Page 3Linked to original sources
PubMed1997

Preliminary results of a phase II study of epirubicin and paclitaxel as first-line treatment in patients with metastatic breast cancer.

Preliminary results of this ongoing phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus epirubicin administered as first-line treatment to women with metastatic breast cancer indicate encouraging response rates and no severe toxicity. Among the 57 patients admitted to this study, 52% had received prior adjuvant chemotherapy (85% with cyclophosphamide/methotrexate/5-fluorouracil), 46% had received radiotherapy, and 30% had received both forms of therapy; 63% of patients were postmenopausal, mainly with poorly differentiated tumors, and 80% presented with > or = 2 metastatic sites. Epirubicin 60 mg/m2 was administered intravenously as a 1-hour infusion followed by paclitaxel 175 mg/m2 infused over 3 hours. Standard premedication was given. Granulocyte colony-stimulating factor support was not used. Neutropenia was evident in 72% of cycles but was not severe. Instances of anemia and thrombocytopenia were rare. Alopecia was universal. All nonhematologic toxicity observed was mild or moderate (peripheral neuropathy, myalgia, nausea, vomiting World Health Organization toxicity grade < 2). At this time, 41 patients are currently evaluable for response, complete and partial remission are evident in seven and 21 patients, respectively. The overall response rate so far is 68%. An additional 12 patients show evidence of stable disease, and one has shown disease progression. Paclitaxel is considered a promising new drug in the adjuvant treatment of patients with metastatic breast cancer. Combining it with epirubicin allows safe administration with no evidence of severe cardiotoxicity. The incidence of adverse cardiac events was much lower than that observed with combinations of paclitaxel and doxorubicin.

Adolescent↗
PubMed1997

Paclitaxel and epirubicin as first-line therapy for patients with metastatic breast cancer.

Paclitaxel (Taxol), has aroused considerable interest for its high single-agent activity in breast cancer and novel mechanism of action. Epirubicin (Farmorubicin), the 4'epimer of doxorubicin (Adriamycin), also has high activity in breast cancer, with the advantage of a lower rate of toxic side effects-especially cardiac effects-compared with its parent compound. The combination of paclitaxel and doxorubicin has yielded response rates between 63% and 94% in phase I/II studies, but authors reported severe cardiac toxic events. The goal for the current study was to evaluate the combination of paclitaxel and epirubicin, focusing mainly on cardiac toxicity. Of a total of 85 patients entered, 68 patients with metastatic breast cancer were evaluable. Nearly 20% had primary metastatic breast cancer with large tumors. Half had received adjuvant chemotherapy. Study medication in Group A consisted of 60 mg/m2 epirubicin given over 1 hour, followed by paclitaxel 175 mg/m2 as a 3-hour IV infusion. In Group B, 90 mg/m2 epirubicin was combined with 175 mg/m2 paclitaxel, delivered as for Group A. The main toxicity in both groups was neutropenia. In Group A, the paclitaxel dose could be escalated to 200 mg/m2 in 15 patients and to 225 mg/m2 in 7 patients; dose reduction due to severe neutropenia was necessary in 11 patients. No cardiac adverse events were reported in Group A. In Group B, only one patient could be escalated to 200 mg/m2 but three patients required a dose reduction. In this group, one patient had a decrease of left ventricular ejection fraction of more than 10% without any clinical signs. Of 43 patients in Group A and 25 in Group B, the response rate was 67% in Group A and 68% in Group B. The duration of response was 8.2 months in both groups. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 or 90 mg/m2 can be safely administered. The response data were encouraging and further evaluation is warranted.

Antibiotics, Antineoplastic↗
PubMed1997

Phase II study of paclitaxel and epirubicin as first-line therapy in patients with metastatic breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane used in routine clinical practice, has aroused considerable interest for its high single-agent activity against breast cancer and for its novel mechanism of action. Epirubicin, the 4' epimer of doxorubicin, is another agent with a high activity against breast cancer and is known for its lower rate of toxic side effects, especially toxic cardiac events, compared with its mother compound. The combination of paclitaxel and doxorubicin yielded response rates between 63% and 93% in phase I/II studies. In these studies, however, the investigators reported severe cardiac toxic events. The rationale for the current study was therefore to evaluate the combination of paclitaxel/epirubicin, focusing mainly on cardiac toxicity. In two groups, 85 patients with metastatic breast cancer entered the study. Approximately 20% of the patients had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication in group A consisted of epirubicin 60 mg/m2 given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2-blockers. In group B, epirubicin 90 mg/m2 was combined with paclitaxel 175 mg/m2, given in the same manner as in group A. Dose escalation to 225 mg/m2 paclitaxel was planned in both groups. The main toxicity in both groups was neutropenia (73% World Health Organization grade 3/4 in group A and 93% in group B). Other hematologic side effects were rare. No febrile neutropenia was reported in group A, but two episodes occurred in group B. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grades 1 and 2). Alopecia was universal. In group A, the paclitaxel dose could be escalated to 200 mg/m2 in 15 patients and to 225 mg/m2 in seven patients. Dose reduction due to severe neutropenia was necessary in 11 patients. No cardiac events were reported in group A. In group B, the paclitaxel dose could be escalated to 200 mg/m2 in only one patient, and no patient reached 225 mg/m2. Three patients needed a dose reduction. In this group, one patient had a greater than 10% decrease in the left ventricular ejection fraction with no clinical signs. In group A, 43 patients were evaluable for response; in group B, 25 patients were evaluable. Thirteen patients were out of protocol with only bone metastasis, and two patients had more than one prior chemotherapy for metastatic disease. The response rate was identical in both groups, with five complete remissions and 24 partial remissions in group A and three complete responses and 14 partial remissions in group B. The duration of response was 8.2 months in both groups. The median cumulative epirubicin dose was 420 mg/m2 in group A and 630 mg/m2 in group B. The combination of paclitaxel 175 mg/m2 and epirubicin 60 or 90 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of this combination-line treatment of metastatic breast cancer is warranted.

Adult↗
PubMed1996

Comparative analyses of bone marrow micrometastases in breast and gastric cancer.

This study is a comparative analysis of the prevalence, absolute number and aggregation status of bone marrow micro-metastases (BMM) between breast (n=234) and gastric (n=102) cancer patients based on a standardized number of 1 X 10(6) bone marrow-derived cells per patient. Additionally, expression of the epithelial cell adhesion molecule E-cadherin was analyzed on disseminated tumor cells. A positive BMM status was demonstrated in 88/234 breast and 45/102 gastric cancer patients. The presence of CK18+ cells positively correlated with parameters of advanced tumor progression in breast, but not in gastric cancer. Interestingly, 25.2% of the node-negative patients already had micrometastatic cells in the bone marrow at diagnosis. Regarding the absolute number of CK18+ cells and the frequency of CK18+ cell clusters, no significant difference was found between the 2 tumor types. However, clusters consisting of more than 10 CK18+ cells (type II clusters) were present exclusively in breast cancer patients. Additionally, co-expression of CK18 and E-cadherin was detectable in 15/21 micrometastases-positive breast but in only 1/9 gastric cancer patients. While prevalence of micrometastatic cells in bone marrow is discussed as an early indicator for systemic disease, aggregation status and a certain antigen profile might be indicative for site-specific differences in the manifestation pattern of solid metastases.

Bone Marrow Neoplasms↗
PubMed1996

[Dynamic MR mammography: is the course of signal intensification suitable for the differentiation of different forms of mastopathy?].

PURPOSE: The capacity of dynamic contrast-enhanced MR mammography to distinguish between different forms and grades of mastopathy according to Prechtel's classification was evaluated in a retrospective study. PATIENTS AND METHODS: MR mammograms of 51 patients with histologically proven mastopathy were retrospectively evaluated in areas subsequently biopsied. RESULTS: Mean values of regressive and hyperplastic types of mastopathy differed significantly no significant differences were found between proliferating and non-proliferating mastopathies or Prechtel grades I-III mastopathy when MRI data obtained with a FLASH 3 D sequence (TR = 8.4 ms, TE = 3 ms, flip angle = 30 degrees at 1.0 T) were compared one minute, three, 5 and 8 minutes after i.v. bolus administration of contrast media (Gd-DTPA, 0.1 mmol/kg body weight). CONCLUSION: Our data indicate that dynamic contrast-enhanced MR mammography does not allow the differentiation of proliferating and non-proliferating mastopathy according to the Prechtel classification. Dynamic MR mammography assessment of breast cancer risk does not seem to be feasible.

Breast↗
PubMed1996

[Technics for the preoperative marking of nonpalpable breast lesions in MRT].

We describe a method of localizing suspicious breast lesions only visible by MRI that does not require additional hardware and can be carried out on any MRI-scanner suited for MR-mammography. We have performed a total of 48 localizations with different techniques: 28 charcoal/Gd-DTPA, 18 with wires and two skin markings. All localizations have been successful; wire localizations provided the best results, since the position of the wire could be corrected under MR-guidance. Until suitable localization- and biopsy coils become available the methods employed by us provide a satisfactory alternative which allows radiologists who perform diagnostic MR-mammography with techniques to carry out precise pre-operative localisations of breast lesions.

Breast↗
PubMed1996

Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity.

Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from a newly developed tumor chemosensitivity assay (TCA) have been correlated prospectively with patient response. In this study, we have used heterogeneity data for standard regimens obtained from 116 breast TCAs to set sensitivity/resistance thresholds which were then used to interpret the results from those with known clinical responses. Assay evaluability was 97% in surgical biopsies. Clinical follow-up of stage III/ IV assessable disease was obtained from 27 breast tumors which were successfully tested for chemosensitivity, including 13 needle biopsies. The ATP-TCA assay predicted response correctly in 22 out of 29 (76%) tumors with clinically evaluable disease, suggesting that it is capable of predicting outcome in individual patients. Assays were performed in seven patients before and after chemotherapy using residual or recurrent tumor tissue. Four cases with initial sensitivity showed a decrease in sensitivity within 6 months of starting chemotherapy, while two others without clinical resistance were still sensitive by TCA. All nine courses of therapy given on the basis of TCA sensitivity resulted in partial or complete responses. Controlled trials of TCA-directed treatment against standardized empirical therapy should be conducted before this technology is widely adopted to assess its impact on rates of response, survival and the cost of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Interim Analysis of a Phase II study of epirubicin and paclitaxel as first-line therapy in patients with metastatic breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to be used routinely in clinical practice, has aroused considerable interest for its high single-agent activity in breast cancer and its novel mechanism of action. The 4' epimer of doxorubicin, epirubicin is an agent with high activity against breast cancer but a lower rate of toxic side effects, especially cardiotoxic events, than its parent compound. Although the paclitaxel/doxorubicin combination has yielded response rates between 63% and 94% in phase I/II studies, some severe cardiotoxic events were reported. The rationale for our study was to evaluate the paclitaxel/epirubicin combination, focusing mainly on cardiotoxicity. In all, 57 patients with metastatic breast cancer entered the study, 28% of whom had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication consisted of 60 mg/m2 epirubicin given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2 antagonists. The main toxicity was neutropenia (World Health Organization toxicity index grade 3/4, 72%). Other hematologic side effects were rare and no febrile neutropenia was reported. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grade 1 and 2). All patients had alopecia. The paclitaxel dose was escalated to 200 mg/m2 in eight patients, four of whom received a further escalation to 225 mg/m2. Severe neutropenia necessitated dose reductions in eight patients. No cardiac adverse events were reported. Of 41 patients evaluable for response, seven had complete remissions and 21 had partial remissions (68%). An additional 12 patients (29%) had stable disease. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of the role of this combination in the first-line treatment of metastatic breast cancer is warranted.

Adult↗
PubMed1995

Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma.

An ATP luminescence assay (TCA 100) was used to measure chemotherapeutic drug sensitivity and resistance of dissociated tumor cells cultured for 6 days in serum-free medium and 96-well polypropylene microplates. Studies were performed with surgical, needle biopsy, pleural, or ascitic fluid specimens using 10,000-20,000 cells/well. ATP measurements were used to determine tumor growth inhibition. Single agent and drug combinations were evaluated using the area under the curve and 50% inhibitory concentration (IC50) results for a series of test drug concentrations. The ATP luminometry method had high sensitivity, linearity, and precision for measuring the activity of single agents and drug combinations. Assay reproducibility was high with intraassay and interassay coefficients of variation of 10-15% for percentage of tumor growth inhibition, 5-10% for area under curve, and 15-20% for IC50 results. Good correlation (r = 0.93) between the area under the curve, and IC50 results was observed. Cytological studies with 124 specimens demonstrated selective growth of malignant cells in the serum-free culture system. Studies with malignant and benign specimens also showed selective growth of malignant cells in the serum-free medium used for assay. The assay had a success rate of 87% based on criteria for specimen histopathology, magnitude of cell growth, and dose-response drug activity. Cisplatin results for ovarian carcinoma are presented for 81 specimens from 70 untreated patients and 33 specimens from 30 refractory patients. A model for interpretation of these results based on the correlation of clinical response with the area under the curve and IC50 results indicates that the assay has > 90% accuracy for cisplatin resistance of ovarian carcinoma. Additional studies are in progress to evaluate the clinical efficacy of this assay.

Adenosine Triphosphate↗
PubMed1995

DNA cell-cycle analysis of cervical cancer by flow cytometry using simultaneous cytokeratin labelling for identification of tumour cells.

DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumour tissue of 53 cervical carcinomas. Epithelial cells were labelled by a fluorescein-isothiocyanate-conjugated cytokeratin antibody (CK6, CK18) to study the influence of contaminating stromal and inflammatory cells on results of cell-cycle analysis of tumour cells. Without identification of cytokeratin-positive cells 30/53 (57%) tumours were found to be DNA-aneuploid compared to 43/53 (81%) after gating for cytokeratin. Only 7 of 15 DNA-multiploid tumours could be detected without cytokeratin staining. In addition, cytokeratin-negative cells, which are found in all tumours, can be used as an internal standard for the calculation of ploidy and for quality control (coefficient of variation, linearity) of each individual sample. Cell-cycle analysis revealed significantly higher S-phase and G2M-phase fractions in cytokeratin-gated compared to ungated samples (13.1% versus 10.0% and 8.0% versus 5.4%; P < 0.001). This difference was more pronounced in DNA-diploid than DNA-aneuploid tumours. In conclusion, about 30% of DNA-aneuploid tumours could only be detected after cytokeratin labelling of epithelial cells. Owing to the identification of cytokeratin-positive cells the influence of non-tumoural cell elements on cell-cycle analysis was reduced markedly. Therefore, in cervical cancer, cytokeratin labelling can optimize both the determination of DNA ploidy and cell-cycle analysis.

Cell Cycle↗
PubMed1995

In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.

This is the first report on the ATP cell viability assay as a chemosensitivity test system for gestational trophoblastic neoplasms (GTN). We obtained chemosensitivity profiles in two established trophoblastic cell lines and four fresh tumors. Ten drugs were tested in vitro in the two cell lines JAR and JEG-3. The IC50 values of the 10 chemotherapeutic agents tested were very similar for both cell lines. The three most active drugs in these cell lines were VP-16, paclitaxel and vincristine. This is the first report on the activity of paclitaxel in trophoblastic cell lines. We furthermore evaluated this assay for chemosensitivity testing in four fresh malignant GTN tumors: one placental site trophoblastic tumor, one chorocarcinoma and two invasive moles. The placental site trophoblastic tumor specimen revealed to be rather chemoresistant in vitro whereas the other three tumors were chemosensitive. From our cell line data we conclude that the ATP cell viability assay is a practicable assay for chemosensitivity testing of GTN cell lines and gives repeatable results. However, the value of this assay for fresh GTN chemosensitivity testing needs to be defined.

Adenosine Triphosphate↗
PubMed1995

[The synergistic effect of delta-aminolevulinic acid and photodynamic laser therapy based on an in vitro model of the ATP tumor chemosensitivity test].

Photodynamic laser therapy (PDT) is under prospective clinical evaluation in gynecology. We used the ATP tumorchemosensitivity assay to detect the efficacy of delta-aminolevulinic acid (ALA) in combination with PDT. Two invasive cervical cancer cell lines were used, C33 and SIHA. The cell-damaging effect was quantified by measuring the intracellular ATP content. The 50% inhibitory concentration of ALA was 760 microM in the cell line C33 and 500 microM in the cell line SIHA. The combination of ALA incubation and PDT was synergistic in both cell lines. After in vitro experiments with this method, the combination is now used in a clinical phase II study. PDT after topical ALA application promises to become a possible alternative for the treatment of preinvasive and invasive malignancies in gynecology.

Adenosine Triphosphate↗
PubMed1995

[Use of photodynamic laser therapy in gynecology].

OBJECTIVE: Dysplasia of the vulva and uterine cervix are often multicentric, tend to recur and have mostly to be treated by surgical procedures. The photodynamic laser therapy (PDT) may be an alternative, which selectively destroys neoplastic tissue after topical delta-aminolevulinic acid (ALA) used as a photosensitizer. METHODS: We measured the distribution of fluorescence in dysplastic and nondysplastic tissue after topical application of ALA in 27 patients with dysplasia. In 3 vulvar and 2 cervical dysplasias, PDT was performed. RESULTS: We could show a selective enrichment of endogenous porphyrins in dysplastic tissues, whereas benign tissue showed no fluorescence. The fluorescence was limited to the mucosa. The heterogeneous fluorescence pattern was influenced by the duration of ALA application. In the treated patients, cytological and clinical parameters showed improvement after use of PDT. The longest recurrence-free interval from treatment up to date is 15 months (range 3-15 months). CONCLUSIONS: After first results of penetration studies and clinical follow-up, PDT after topical ALA application seems to be a good alternative to surgical procedures in dysplastic changes of the genital tract.

Adult↗
PubMed1994

Evaluation of paclitaxel (taxol), cisplatin, and the combination paclitaxel-cisplatin in ovarian cancer in vitro with the ATP cell viability assay.

This study evaluates the in vitro sensitivities of 42 ovarian cancer specimens to the new anticancer agent Paclitaxel (taxol, Tx), cisplatin (DDP), and the combination Tx-DDP with the adenosine triphosphate cell viability assay (ATP-CVA). In vitro response is defined by > or = 50% ATP decrease compared to untreated controls 6-7 days after drug treatment with 20% of the peak plasma concentration (PPC). Response rates were 12% to Tx, 19% to DDP, and 27% to Tx + DDP. The mean IC50's of Tx, DDP, and the combination Tx-DDP were (2.6x, 1.0x, and 0.38x PPC, respectively). The mean inhibition of cell viability was significantly greater with drug combinations compared to single drugs. In 7/11 tumors synergistic effects and in 2/11 additive effects were found between Tx and DDP. We conclude that based on ATP-CVA in vitro results, Tx-DDP shows significantly better activity compared to each of the single drugs in ovarian cancer.

Adenosine Triphosphate↗
PubMed1994

Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up.

We examined bone marrow aspirates from 100 metastasis-free primary breast cancer patients. In 38/100 patients (38%), tumour cells were detected in the marrow using an immunocytochemical technique with a cocktail of two monoclonal antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38 (39%) tumour cell-positive patients have since relapsed, but only 9/62 (15%) tumour cell-negative patients. The median interval between tumour cell detection and relapse was 11.4 months. No statistically significant correlation existed between tumour cell presence and 'established' prognostic factors. However, relapse-free survival was significantly shorter in tumour cell-positive patients. Multivariate analysis showed tumour cell presence as a strong, significant prognostic factor for relapse-free as well as overall survival. We conclude that screening for tumour cells in bone marrow of primary breast cancer patients identifies high-risk patients for early relapse. In particular, patients with node-negative tumours who have tumour cells in their bone marrow may require subsequent systemic therapy.

Adult↗
PubMed1994

Comparison of paclitaxel and docetaxel (Taxotere) in gynecologic and breast cancer cell lines with the ATP-cell viability assay.

The in vitro effects of paclitaxel (Tx) and docetaxel (Taxotere, Txt) are compared in this study using the adenosine triphosphate cell viability assay (ATP-CVA) in 14 cancer cell lines. Eleven cell lines were sensitive and three were partially sensitive to paclitaxel. Nine cell lines were sensitive, three were partially sensitive and two were resistant to docetaxel. Mean IC50s were 3.7-660 ng/ml paclitaxel and 5.4-540 ng/ml docetaxel. In five sensitive cancer cell lines docetaxel was more active than paclitaxel, and in six sensitive cell lines paclitaxel was more active than docetaxel on a concentration basis. Two cell lines were sensitive to paclitaxel and resistant to docetaxel. In one cell line the two compounds had similar activities. In the ATP-CVA, paclitaxel and docetaxel are very active and are partially non-cross-resistant.

Adenocarcinoma↗
PubMed1994

Contrast-enhanced MR imaging of the breast: comparison of two different doses of gadopentetate dimeglumine.

PURPOSE: To optimize detection and diagnosis of breast lesions with contrast-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: A three-dimensional fast low-angle shot pulse sequence was used for a group comparison consisting of 76 high-dose (0.16 mmol gadopentetate dimeglumine per kilogram of body weight) and 76 low-dose (0.1 mmol/kg) examinations. Intraindividual comparisons were possible in a subgroup of 20 patients. RESULTS: Enhancement with the high dose was about 1.5 times higher for benign and malignant tissues. With the lower dose, no false-positive findings could be avoided and definition of a threshold that excluded false-negative findings was problematic. Conspicuity of malignant lesions was much improved with the higher dose (a good to excellent rating in 81% vs 26% with the lower dose). Three small foci were visible only with the higher dose. CONCLUSION: The higher dose of contrast material allowed much better results. Dose comparison studies are also recommended for other techniques.

Breast↗