Biomedical subjects
H Rainer
Publications and source records attributed to H Rainer.
[Mitoxantrone in the primary treatment of metastasizing breast cancer].
25 females (57.7 +/- 11.1 years) and 1 male (71 years) with histologically verified metastasizing breast cancer were submitted to mitoxantrone therapy. Secondary tumours were found in following organ systems: bone: 19 cases; lung: 13 cases; liver: 6 cases; skin: 5 cases; locoregional and nodal: 5 cases; brain: 1 case. All patients showed normal bone marrow and heart function before commencement of treatment. Mitoxantrone was given in form of a 30-minute infusion at a dosage of 14 mg/m2. In 4 patients dosage was increased to 20 mg/m2. Treatment cycles were repeated every 3 weeks according to peripheral blood counts. All patients were cardiologically monitored throughout the study by means of electrocardiogram, systolic time interval measurement and radionuclide angiography. The mean observation period was 169 +/- 98 days. The response of the patients was as follows: 1 complete remission, 5 partial remissions, 4 unchanged disease and 16 progressive disease. Side effects were normally mild; only nausea, leucopenia and moderate hair loss were of clinical relevance. Cardiac decompensation was not observed. No significant electrocardiographic alterations were found throughout the study. Results of systolic time interval measurements (PEPI, PEP:LVET) and radionuclide angiography (LVEF) gave evidence of moderate depression of heart function. In view of the optimal benefit/risk ratio of mitoxantrone this drug could be used in combined modality treatment schedules in metastasizing breast cancer.
Mitoxantrone for the treatment of advanced breast cancer: single-agent therapy in previously untreated patients.
Mitoxantrone (dihydroxyanthracenedione) is a substituted anthraquinone with a similar spectrum of activity to adriamycin in experimental tumours. One hundred and thirty-four patients with advanced breast cancer and no prior chemotherapy for advanced disease were treated with mitoxantrone (14 mg/m2 i.v. q 3 weeks), of whom 99 are presently evaluable for response and all for toxicity. Six patients achieved a complete response and 29 a partial response, the overall response rate being 35% (95% confidence limits, 25-45%). Median time to treatment failure was greater than 46 weeks. Mitoxantrone was well tolerated, myelosuppression being the dose-limiting toxicity. The most frequent nonhaematological toxicities were nausea and vomiting (40%), but these were rarely severe. Total alopecia occurred in only 6 patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative mitoxantrone doses of 174-256 mg/m2. Mitoxantrone offers comparable efficacy and less acute toxicity than the most active currently available single agents in advanced breast cancer.
[Chemotherapy of small cell bronchial carcinoma].
Many cytotoxic agents exhibit response in oat cell lung cancer. According to response rates those substances my be divided into 3 subgroups. Combination of chemotherapeutic drugs is considerable more active as compared to single agent therapy. Actuarial survival was significantly improved by chemotherapy and is related to dosages and the absolute number of cytotoxics used. Sequential chemotherapy with sequential administration of non-cross resistant schemes seems to be the optimal therapeutic strategy at present time. A ten-fold increase of survival has been shown including a small percentage of long term survivors. It seems likely to assume that those therapies combined in an optimal manner without dose-reductions during induction therapy will further improve survival and percentage of long term survivors.
A prospective study of relationships between benign gastric ulcer, Candida, and medical treatment.
Results of a multicenter prospective study on the relationships between benign gastric ulcer, Candida, and medical treatment is reported. In a group of 66 patients, mycetes were seen in six cases (9.1%). Candida-contaminated ulcers were diagnosed solely by histological examination, with periodic acid-Schiff staining being more effective than hematoxylin and eosin staining. All contaminated ulcers were healed by treatment either with cimetidine alone, or combined cimetidine-carbenoxolone, without antimycotics. No cases of Candida-contaminated ulcers were seen after 6 wk of treatment. The finding of contamination was more common in older patients. Under the conditions of our study, Candida-contamination of benign gastric ulcers does not affect the rate of healing, does not need specific treatment, and has no particular endoscopic features. Cimetidine or carbenoxolone treatment was not associated with persistence of the fungus.
Mitoxantrone as first-line chemotherapy for advanced breast cancer: results of a European collaborative study.
A total of 134 patients with advanced breast cancer and no prior chemotherapy for advanced disease were treated with mitoxantrone, 14 mg/m2 intravenously every 3 weeks. Of these, 99 could be evaluated for response and all for toxicity. Six patients achieved a complete response and 29 a partial response, the overall response rate being 35% (95% confidence limits 25% to 45%). The median time to treatment failure was greater than 46 weeks. Mitoxantrone was well tolerated. Nausea and vomiting occurred in 40% of patients, but these were seldom severe. Total alopecia occurred in only six patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative doses of 174 to 256 mg/m2. Mitoxantrone offers comparable efficacy and less acute toxicity than the most active single agents currently used in the treatment of advanced breast cancer.
[Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study].
From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.
Prekallikrein, HMW-kininogen and factor XII in various disease states.
The behaviour of prekallikrein (PKK), factor XII, high molecular weight kininogen (HMWK) and kallikrein-inhibitor (KK-I) in 367 patients with various diseases is described. Malignancies lead to elevation of factor XII and KK-I, and reduction of PKK. The effect is more pronounced in patients with metastases. In renal diseases also one or more of the above mentioned parameters are abnormal. Defects requiring dialysis treatment significantly impair the contact factors. In this group low levels of PKK, Factor XII and HMWK and increased KK-I are common. In chronic renal disease patients, only F XII and KK-I are elevated, whereas PKK and HMWK are normal. Kidney transplantation leads to a rise in KK-I and reduction of PKK and HMWK. The values almost normalize few days after the operation. Factor XII, slightly increased immediately after transplantation, remains high in long term transplant recipients, whereas HMWK falls below normal. In liver disease patients, acute and chronic hepatitis, cirrhosis of the liver and coma, PKK is reduced. In cases with acute hepatitis PKK raises with recovery. Cirrhosis and coma lead to low HMWK and factor XII concentrations. KK-I is mostly affected during acute hepatitis, and is then highly increased. Our results clearly demonstrate that the biologic activity of one or more of contact factors is affected in many diseases.
[Pilot studies with aclacinomycin in patients with breast cancer or gastrointestinal tumors].
Aclacinomycin (ACM), a new anthracycline antibiotic compound, was given intravenously q x 3 to 6 weeks in a dosage of 4 x 60 mg/4 days to 10 patients with metastasizing breast cancer and 5 patients with gastric carcinoma. Breast cancer patients, prior to ACM had extensive cytotoxic and hormonal treatments, gastric cancer patients received ACM as a first chemotherapeutic tumor treatment. No life-threatening hematologic toxicities could be noticed. All patients experienced moderate to severe gastrointestinal toxicities. No patient had considerable hair loss. 4 patients showed clinical signs of cardiac dysfunction: 1 ECG changes, 4 developed edema of lower extremities, 2 developed pericardial effusion. Moreover, 1 patient developed significant elevation of the pulmonary capillary wedge pressure (PCW) and prolongation of the systolic time intervals indicating pulmonary congestion grade I to II (Braunwald). No significant increase in heart volume was registered. Clear signs of cardiotoxicity could be demonstrated in patients pretreated with adriamycin exclusively. In animal experience, ACM had been reported as less cardiotoxic as compared to adriamycin. Present studies seem to indicate ACM being considerably cardiotoxic at relatively low cumulative dosages. Among the 15 patients there was one with metastatic breast cancer pretreated with adriamycin and resistant to that drug in whom partial remission was achieved. The other patients did not objectively respond to ACM therapy. 3 out of 5 patients with gastric cancer had stabilisation of the disease but no objective response.
Clinical and experimental aspects of hormone receptors in breast carcinoma patients.
Estrogen (ER) and progesterone (PgR) receptor contents were determined in 214 patients with primary mammary carcinoma. Premenopausal and postmenopausal females (43 and 48%, respectively) were found to be ER and PgR positive. ER levels between 100 and 500 fmol/mg protein were observed in 37% postmenopausal and 14% premenopausal patients, respectively. ER distribution between lymph node-positive and -negative patients did not differ significantly. Subjects without detectable ER had recurrences earlier than did subjects with ER. On the other hand, no differences in recurrence rates were noted when PgR-positive and -negative patients were compared. In addition, the determination of ER did not permit selection of patients for adjuvant cytotoxic chemotherapy. Furthermore, the action of tamoxifen was investigated in the rat pituitary as a model system. Tamoxifen was found to act as antiestrogen at the level of transcription by inhibiting the accumulation of estrogen-stimulated preprolactin mRNA. Combined data suggest that patients with positive lymph nodes and positive receptors may benefit from combined endocrine plus cytotoxic adjuvant chemotherapy.
The value of prognostic parameters for the stratification of advanced breast cancer patients.
One hundred seventy-five patients with metastatic breast cancer, treated with a combination chemotherapy (Cooper regimen), were analyzed retrospectively to identify the value of the traditional prognostic parameters (disease-free interval; menopausal status; dominant site of metastatic lesion) for the stratification of patients before randomization. Response rate and survival time were not significantly affected by the disease-free interval and menopausal status. A significant difference was detected among the three categories of dominant disease (locoregional; osseous; visceral). However, an estimate of total extent of disease (according to Swenerton) was found to be the most important factor for predicting response and survival time after combination cytotoxic treatment. The differences between the dominant size of metastatic disease are mainly influenced by different size of metastatic spread. Therefore, there is found a significant correlation between the different types of dominant lesions and total extent of disease. In conclusion, the particular sites of metastatic spread seem to be of less importance than overall extent of disease in predicting the outcome. A critical evaluation of the three traditional stratification parameters and introduction of a semiquantitative estimation of total tumor burden as a new stratification parameter seems to be necessary when planning and comparing future trials.
Plasmapheresis in patients with advanced malignant disease: a pilot study.
Plasmapheresis has been performed in 16 patients with advanced malignant disease (12 malignant melanoma, 2 breast cancer, 2 colon cancer). Up to 3,000 ml of plasma (range 1,650-3,000 ml) have been replaced by one single plasma exchange. Side effects observed in about 50% of the patients were mainly nausea and chills. Serum proteins including acute phase reactants were monitored before and 2, 4, and 7 days after plasma exchange. A transient change of these proteins was observed in the first days, but, later on, pretreatment values were always retained. Peripheral blood lymphocyte blastogenic response to mitogens was increased in 5 out of 9 patients 7 days after plasma exchange. In 7 out of 9 patients pretreatment serum was found inhibitory to autologous lymphocyte reactivity to mitogens. Furthermore, plasmapheresis was found to decrease significantly the blocking effect of patients' sera on normal donor lymphocyte reactivity. Plasmapheresis was found tolerable in all patients treated, but without any clinical efficacy. Further studies are warranted to establish the therapeutic value of plasma exchange in patients with advanced malignancies.
Effectiveness of postoperative adjuvant therapy with cytotoxic chemotherapy (cytosine arabinoside, mitomycin C, 5-fluorouracil) or immunotherapy (neuraminidase-modified allogeneic cells) in the prevention of recurrence of Duke's B and C colon cancer.
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[Developments in the serological diagnosis of malignant diseases].
The present study gives an evaluation of carcinoembryonic antigen (CEA), macrophage electrophoretic mobility test (MEM), sialyltransferase, galactosyltransferase isoenzyme (SGT), ribonuclease and reverse transcriptase as diagnostic aids in malignant diseases. CEA and sialyltransferase are of certain value in the monitoring of cancer, as their values in the serum may rise before progression of disease or relapse. Both tests are not reliable parameters in the early diagnosis of malignancy. Our results with regard to the MEM test have not proved in any way useful in the diagnosis of cancer. Our preliminary results appear to indicate that, provided further simplification of the method can be achieved, SGT isoenzyme determination seems to be a better means of diagnosing cancer. In view of inherent-methodological difficulties reverse transcriptase has, at present, no clinical application in the diagnosis of cancer.
[Oestrogen receptors and prognosis in breast cancer].
The determination of oestrogen receptors seems to be of prognostic value in the radically-operated breast cancer patient. Patients with negative receptor values exhibit early recurrence in a significantly higher percentage of cases than those with positive values. The prognostic implications of oestrogen receptor determination seem to be even higher than an assessment of axillary lymph node involvement. In metastatic breast carcinoma a correlation exists between response to hormonal therapy and receptor assay. The clinical implications for therapeutic management are discussed.
[Phase 2 study with cis-dichlorodiaminoplatinum (II) in advanced solid tumors].
cis-Dichlorodiammineplatinum(II) was administered in 23 patients with far advanced solid malignancies using a dose schedule of 50 mg/m2 every 3 weeks. All patients previously had progressive disease using conventional cytotoxic therapies. More than 50% of the patients had been pretreated with at least four different drugs, 9 patients had additionally been irradiated. IN 4 patients there was objective tumor regression (duration 1-4 months); in 7 patients tumor progression could be stopped for at least 1 month; 12 patients did not respond. By sufficient fluid administration combined with electrolyte substitution, furosemide and mannitol, no severe toxic side effects were encountered.
[Prognostic factors in the drug therapy of metastasizing breast cancer].
175 patients with metastatic breast cancer, treated with chemotherapy, were analyzed retrospectively to identify the characteristics of prognostic importance in predicting response to chemotherapy and survival from onset of the chemotherapy. The most significant factors were the sites of metastatic disease and an estimate of the total extent of disease.
[Specific immunotherapy in metastasizing breast cancer combined with chemotherapy. A prospective randomized study].
40 patients with metastasized mamma carcinoma were immunized with T-antigen, in addition to cytostatic therapy. A second group of 40 patients received cytostatics only. No improvement of remission rates could be obtained by additional immunotherapy with T-antigen.