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O Schlappack

Publications and source records attributed to O Schlappack.

18 recordsLinked to original sources
PubMed1995

Pharmacokinetics of 4'-O-tetrahydropyranyladriamycin given on a weekly schedule in patients with advanced breast cancer.

Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4'-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m2 THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t1/2 alpha), 3.15 min; terminal elimination half-life (t1/2 gamma), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml-1mg-1 m-2, resulting in a mean plasma clearance of 86.9 1h-1 m-2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4'-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadriamycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r = 0.800, P < 0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule.

Adult↗
PubMed1994

[A critical consideration of the combined radiochemotherapy of head and neck tumors].

PURPOSE: Advanced tumors of the head and neck are often treated with combined radiochemotherapy. The chemotherapeutic agents used should be active in this tumor type and its adverse effects should not overlap with those of the radiation treatment. METHODS: Published studies were reviewed and discussed on the basis of these principles. RESULTS: Initially, single agents such as 5-fluorouracil (5-FU) and methotrexate were used in combination with radiotherapy. These combinations caused an improved local tumor control but also an increased mucosal reaction. For mitomycin C it has been shown in a randomized trial that local tumor control was improved without concomitant increased normal tissue toxicity. Also cisplatin and carboplatin were studied in combination with radiotherapy. Unfortunately, there are no results of randomized studies available but these agents do not seem to increase mucosal toxicity. The standard chemotherapy of squamous cell carcinomas of the head and neck is cisplatin and 5-FU. Many studies have been conducted with this chemotherapy in combination with radiotherapy. To this day it has not been shown that the results of an effective radiation treatment or an effective chemotherapy can be improved by these experiments. The explanation for that is that either the chemotherapy or the radiotherapy cannot be given at full dose because the regimen would become too toxic. CONCLUSION: 5-FU containing polychemotherapy regimens should not be combined with radiation any more because it is known that 5-FU increases the mucosal reaction. Agents that could be studied in the future either alone or in combination with cisplatin or carboplatin are etoposide and taxol.

Carcinoma, Squamous Cell↗
PubMed1992

[Differential prognosis of patients with breast cancer with pleuritis carcinomatosa and with pulmonary lymphangiosis carcinomatosa].

The retrospective analysis of 672 consecutive patients with breast cancer revealed malignant pleural effusion and lymphangitic carcinomatosis of the lung to be the sites of first relapse of the disease in only 2% and 1%, respectively. In half of the 10 patients with malignant pleural effusions evaluable for survival, generalization of the disease was recorded at 51 months (range 0-197 months); the corresponding data for patients with lymphangitic carcinomatosis of the lung (n = 7) were 19 months (range 9-44 months). This difference was statistically significant (p < 0.05). The median survival of patients with pleural effusions and with lymphangitic carcinomatosis of the lung was 22 and 8 months, respectively (n.s.).

Adult↗
PubMed1991

Complete remission of metastasised clear cell sarcoma of tendons and aponeuroses.

Clear cell sarcoma of tendons and aponeuroses is a rare disorder which originates from migrated neural crest cells. It tends to local recurrences and dissemination and the prognosis has to be considered as poor. Based on a small series of patients, a wide surgical excision of the primary tumour or amputation are the therapies of choice. Radiotherapy might be of some value as an adjuvant treatment but radiotherapy and chemotherapy are of little value in the treatment of the advanced disease. Because of the lack of treatment alternatives we treated a 40-year-old female patient with disseminated clear cell sarcoma with interferon-alpha 2b (IFN-alpha 2b) perilesionally after several courses of systemic chemotherapy and radiotherapy had failed. After 4 months of therapy the patient came into a complete pathological remission which lasted for 17 months. A relapse of round cell sarcoma on both tumour sites was then noted. This outcome shows that IFN-alpha 2b was able to induce a complete remission in clear cell sarcoma and might have altered the natural course of the disease. IFN-alpha should be studied as adjuvant therapy after surgery of primary clear cell sarcoma and as a first-line palliative treatment in disseminated disease.

Adult↗
PubMed1991

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma].

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Phase I-II study on weekly administration of pirarubicin in patients with metastatic breast cancer.

A phase I-II study of weekly low-dose pirarubicin was performed in 19 patients with advanced breast cancer. The goal was to establish the optimal dose intensity, i.e., the maximal dose applicable at tolerable toxicity within the intended schedule. Each of the four different dose groups used (20, 24, 25, and 27 mg/m2) comprised 4-5 patients. In over 47% of patients, objective remissions were obtained (confidence interval 26%; 71%) including one complete and eight partial remissions; the median duration of remission was 41 weeks (range 16-72), and the median time to reach remission was 12 weeks (range 6-36). Efficacy of treatment was more dependent on prior chemotherapy than on pirarubicin dosage. The weekly i.v. push injection of the drug was easily applicable at an outpatient clinic and well tolerated. WHO grade 3 was the highest toxicity observed for leukopenia (3/19), leukopenia associated with infection (1/19), nausea/vomiting (2/19) and alopecia (6/19). More severe myelosuppression was avoided by interrupting the weekly application until recovery of leukocytes to greater than or equal to 3.5 x 10(3)/mm3. No clinical signs of cardiotoxicity were observed. Generally, mild to moderate signs of cardiac dysfunction acquired during therapy were detected by special cardiac monitoring. Only in 3 of 19 patients was a cumulative dose of more than 550 mg/m2 surpassed. This was accepted as the upper limit for conventional anthracycline therapy. The median cumulative dose applied was 325 mg/m2/week (range 58.2-800.0). Because of maldistribution of prognostic factors, no dose-response relationship could be established. With respect to the total time for which each patient was studied, the dose group of 27 mg/m2 achieved the highest dose intensity with a median of 17.4 mg/m2/week (range 13.5-22.4). Therefore, the dosage of 27 mg/m2/week is recommended to be used in further phase II-III trials of weekly applied pirarubicin.

Adult↗
PubMed1989

Small bowel function after surgery for chronic radiation enteritis.

The retention of the gamma-emitting 75Se-homotaurocholic acid (SeHCAT) after 72 and 168 h was assessed in 10 patients after ileal resection for radiation injury (group I). 6 patients suffering from chronic postirradiation diarrhea (group II) and 6 patients in whom the ileum had been resected for other indications (group III) were also examined. The retention of SeHCAT was abnormally low (less than 50%) in all cases after 72 h and below 20% in 19 out of 21 cases after 168 h. The length of resected small bowel (groups I and III) was inversely related with SeHCAT retention after 72 h (r = 0.63; p = 0.015), but not after 168 h. There was no correlation between the diarrhea score and the extent of bowel resection, SeHCAT retention or xylose absorption. Hydrogen breath test with lactulose revealed a significantly shortened orocecal transit time in group I, compared to groups II and III. Xylose absorption was significantly reduced in patients with positive 5 g xylose-H2 breath test. In groups I and III, however, xylose absorption tended to improve with increasing time interval following resection (r = 0.79; p = 0.003). It is concluded that radiation injury in addition to small-bowel resection contributes significantly to malabsorption and diarrhea in patients after ileal resection for radiation sequelae. The chronic radiation damage seems to act mainly through impaired motility.

Body Weight↗
PubMed1988

[High dosage and intermediate dosage cytosine arabinoside in the treatment of secondary leukemias].

Patients with secondary acute myeloid leukaemia (AML) following treatment with alkylating agents and/or radiation show a poor response to standard induction therapy. Between 1983-1987 8 consecutive patients were treated with high-dose cytosine arabinoside (HD-ARA C; 3 g/sqm twice daily for 6 days) or intermediate-dose cytosine arabinoside (ID-ARA C; 0.5 g/sqm twice daily for 6 days). Complete remission was achieved in 3 patients (HD-ARA C: 2/3l; ID-ARA C: 1/5) and partial remission in 3 patients (ID-ARA C: 3/5). One patient (HD-ARA C) died during prolonged aplasia, one patient (ID-ARA C) proved refractory to treatment. The respective duration of remission in the 3 responsive patients was 3, 7 and 8 months. The probability of survival of the whole group was 50% after 12 months and 25% after 24 months. Our results confirm the efficacy of monotherapy with ARA C in the treatment of secondary AML. Consolidation therapy with ID-ARA C for 4 days seems to prolong remission.

Adult↗
PubMed1988

Toxicity and response to high-dose ifosfamide + mesna as salvage therapy for advanced breast cancer.

Twenty-six cycles of high-dose ifosfamide + mesna (HD-IFO + M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO + M over 24 h appeared to be the best tolerated. One partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.

Adult↗
PubMed1988

[Diagnostic imaging of hemangiopericytomas].

Eight patients with histologically verified hemangiopericytomas were examined by conventional radiographic techniques (plain films, angiography including cavography) as well as by duplex sonography, CT and MRI. These imaging techniques detected solid tumors with cystic compartments. A typical computed tomographic finding was intensive contrast enhancement within the tumor. Duplex sonography revealed blood flow in the periphery of the tumor. In contrast to reports by other authors no tumor calcification was found by plain film radiography.

Abdominal Neoplasms↗
PubMed1987

Surgical therapy of radiation-induced small-bowel lesions. Report of 34 cases with a high share of patients with combined chemotherapy.

Operations on irradiation-injured bowel are rare, bear a high postoperative mortality, and the procedure of choice (resection vs bypass) is still controversial. Thirty-seven operations on small bowel for late effects of irradiation in 16 years were analyzed retrospectively. Fifty-one percent of the operations were performed in the last four years. Ovarian cancer treated by a combination of radiotherapy and chemotherapy was the most frequent underlying disease of 20 patients (58%) followed by carcinoma of the cervix (eight [24%] of the patients). The median latent period between irradiation and surgery was eight months after the combined radiotherapy/chemotherapy, and 12 months after radiotherapy alone. Thirty operations (81%) were done for small-bowel stricture, four for fistula, and three for perforation. Bypass was performed in 17 patients and resection in 16. Complications (fistula, peritonitis, perforation) occurred after 13 operations (35%). All three patients who developed peritonitis died (mortality, 8.1%): two after resection and one after bypass. Suture-associated complications occurred in three (23%) of 13 cases after single-layer and in three (35%) of 17 cases after two-layer anastomoses. Ten patients are still alive two to 76 months (median, 32 months) after operation, six of them free of tumor. All are underweight and suffer from diarrhea (four to 12 stools per day). Pernicious anemia developed in all six patients surviving more than two years.

Adult↗
PubMed1987

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer.

This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n = 22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n = 28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2-54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p less than 0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a "shifting" of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Electron beam therapy in treatment of parotid neoplasm.

In a retrospective analysis, 42 patients with malignant primary tumor of the parotid gland were evaluated considering survival, local recurrence and tolerance of treatment. All patients referred to radiotherapy were treated by electron beam (10-15 MeV) and followed for more than 5 years. Postoperative radiotherapy after radical operation, with no macroscopic disease, was performed in 18 patients, 7 of whom were treated by radical re-operation and radiation of a recurrent parotid neoplasm. In these groups, the local recurrence rate was 4/18 (22%) and 2/7 (29%), the 5-year survival rate was 9/18 (50%) and 5/7 (71%). In 17 patients, radiotherapy started with gross tumor left behind. This group showed a local recurrence rate of 10/17 (59%) and a 5-year survival of 7/17 (41%). Treatment was well tolerated with no major sequelae. Local tumor control and its impact on survival is discussed.

Adult↗
PubMed1986

[Surgical therapy of late radiation sequelae of the gastrointestinal tract].

Fifty-six operations for intestinal complications of radiation therapy were performed in 48 patients at the Second Surgical Clinic, University of Vienna between 1971 and 1985. The lesions were located in the small bowel (n = 32), the colon and rectum (n = 27) and the duodenum (n = 2). The incidence of the operations increased during the fifteen-years-period, 48.2% being performed in the last five years. 96% of the patients were females, the most frequent cause for irradiation was ovarian cancer (39.6%), followed by cervical (27%) and endometrial cancer (16.7%). 20 Patients (39.6%) had also been treated by chemotherapy. Ovarian cancer as underlying disease (56%) and chemotherapy (56%) were more frequent in small bowel lesions, than in other locations. The radiation damage presented as stenoses (n = 38), fistulas (n = 13), perforations (n = 3), one rectal ulcer and one hemorrhagic proctitis. Resection with end-to-end-anastomosis (n = 15) and bypass (n = 14) were the operations most frequently performed on the small bowel, whereas most colonic and rectal lesions were treated by colostomy alone (n = 14). The postoperative course was complicated by fistulas in 7 patients, by peritonitis in 5, by pulmonary embolism in one and duodenal ulcer perforation in another case. Six patients died postoperatively (10.7%), 5 because of peritonitis. After small bowel resection complications occurred in 4 cases, and two (13%) of the patients died. Bypass in small bowel lesions performed as well as resection: 5 complications and one death (7%) occurred. Single layer suture technique performed better than two layer anastomoses. Eighteen operations with single layer anastomoses resulted in 16.7% complications and no death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Evidence against the adenosine-catecholamine antagonism under in vivo conditions.

Experiments were carried out in anaesthetized, thoracotomized dogs. The dose dependent positive inotropic and chronotropic effects of intracoronary (i.cor.) infusions or bolus injections of isoproterenol (ISO) were neither antagonized by adenosine (0.46, 1.0, and 2.91 x 10(-5) mol/l) nor by the adenosine analogue N6-phenylisopropyl-adenosine (PIA, 3.23 x 10(-7) mol/l). The results indicate, that adenosine and PIA do not have any antagonistic effects on isoproterenol induced positive inotropy and chronotropy in the intact dog heart. Consequently it can be assumed that an adenosine-catecholamine antagonism is of no physiological relevance.

Adenosine↗
PubMedDate not supplied

Comparison of the effects of dihydroergotamine and ergonovine on functional changes caused by beta-adrenergic stimulation in normally and underperfused canine myocardium.

We studied the effects of dihydroergotamine (DHE) and ergonovine on myocardial function in normally perfused myocardial areas and in myocardial areas with restricted coronary flow. Regional function at rest and during isoproterenol (ISO)-induced cardiac stimulation was assessed by two pairs of piezoelectric transducers. Constriction of the circumflex branch with a decrease in coronary blood flow from 24.9 +/- 2.6 to 18.1 +/- 2.2 ml/min had little effect on resting regional function. Intravenous bolus injection of ISO (0.5 microgram/kg) prior to constriction induced a marked decrease in end-diastolic segment length and an increase in percentage shortening. Intravenous bolus injection of ISO (0.5 microgram/kg) after constriction of the circumflex branch induced transient regional dysfunction, as shown by a maximum decrease of percentage shortening by 54.4% in the underperfused area. Intravenous infusion of DHE (2 micrograms/kg; 5 min) did not significantly affect resting function and effectively inhibited ISO-induced regional dysfunction. This improvement in regional function during ISO-induced cardiac stimulation can be attributed to the fact that DHE decreased heart rate and left ventricular power, thus reducing myocardial oxygen demand and improving the energetic situation in the underperfused myocardium. In contrast, ergonovine (5 micrograms/kg; 5 min) induced an impairment in regional function in both segments at rest and further aggravated ISO-induced transient dysfunction. The present study confirms the adverse effect of ergonovine on blood flow and regional function in underperfused myocardial areas and demonstrates a beneficial effect of DHE on regional function in underperfused myocardial areas during ISO-induced cardiac stimulation.

Animals↗