Immunoreactivity of patient with colorectal cancer metastasis after immunisation with anti-idiotypes.
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Biomedical subjects
Publications and source records attributed to H Samonigg.
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In a phase II study, 77 patients with metastatic breast cancer were treated with pirarubicin, 70 mg/m2 iv every 3 weeks. Most of them had received prior hormonal (n = 39) and/or chemotherapeutic drug treatment for advanced disease, including anthracycline-containing regimens in 17. After a median of 5.5 treatment cycles (range 1-14), objective tumor response was seen in 22/71 (31%) evaluable patients (4CR, 18 PR). Stable disease occurred in 34 (48%) patients, whereas the tumor progressed in 15 (21%). Significant hematologic toxicity (WHO grade III-IV) requiring interval and/or dose adjustments was observed in 41 (58%) patients. Other treatment-related side effects were generally mild, and included alopecia in 52 (73%), nausea and/or emesis in 50 (70%), and stomatitis and diarrhea in 3 patients each. There was no treatment-related death, nor was there any evidence of cardiac toxicity thus far. In summary, the early results of this trial suggest that pirarubicin is an active and rather well tolerated drug in pretreated patients with advanced breast cancer.
In a phase II study, 35 patients with advanced breast cancer were treated with 4'-O-tetrahydropyranyl-doxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3-15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%-75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21 - 77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III-IV) and thrombocytopenia (9 patients, WHO grade II-IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II-III. Other treatment-related side effects included alopecia (WHO grade II-III) in 26 patients and stomatitis and diarrhea (WHO grade I-III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700-1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.
This study was performed to evaluate the acute effects of two anthracycline derivatives, doxorubicin and 4'O-tetrahydropyranyl-doxorubicin [(THP)-doxorubicin], on the conduction intervals, heart rate and refractoriness of isolated spontaneously beating guinea-pig hearts using a high-resolution ECG recording technique (SST-ECG). Doxorubicin as well as (THP)-doxorubicin were added to the perfusate in increasing concentrations of 0.1, 1 and 10 microM. Doxorubicin did not significantly alter the heart rate or conduction intervals. Only the rate-dependent QT interval was significantly shortened under the influence of 10 microM doxorubicin. In contrast, 10 microM (THP)-doxorubicin led to a significant reduction in the heart rate (-13% +/- 3%; P less than 0.01, n = 7) and to a prolongation of atrioventricular conduction time (24% +/- 10%; P less than 0.05, n = 7). The rate-dependent repolarization period (QT interval) was only insignificantly shortened in the presence of 10 microM (THP)-doxorubicin. The maximal following frequencies of each part of the conduction system were not changed by 10 microM doxorubicin. In the presence of (THP)-doxorubicin, the maximal following frequency of the ventricular myocardium was increased by as much as 36% +/- 8% (P less than 0.01, n = 7), indicating a shortening of the effective refractory period of the ventricular myocardium (V-ERP). These results show that the activation of (THP)-doxorubicin resembles the effects of Ca-antagonistic compounds on the heart (i.e. decrease in the spontaneous sinus rate and prolongation of the AV-nodal conduction interval). Changes in the QT interval exerted by doxorubicin and the shortening of the ventricular effective refractory period by (THP)-doxorubicin may indicate an alteration of the K(+)-conductance of the membrane. As the acute electrophysiological effects of doxorubicin and (THP)-doxorubicin are modest and occur only at excessive concentrations (10 microM), a direct influence on the generation of arrhythmias in healthy hearts is unlikely.
Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.
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.
Twenty-four patients with metastatic thyroid cancer were treated with aclarubicin intravenously at a dose of 25-30 mg/m2 daily for 4 days and treatment was repeated every 3 weeks. None of the patients had previously received chemotherapy. Twenty-three patients received two or more treatment cycles and were evaluated for their response. One complete remission and four partial remissions were noted (objective remission rate 22%). Mean survival time was 57 weeks. Side-effects were evaluated in 24 patients with 18 patients receiving prophylactic antiemetic therapy. Nausea was observed in 18 (75%) and vomiting occurred in three patients (13%). In 15 patients (63%) there was mild myelosuppression. We conclude that aclarubicin alone represents an effective therapy in patients with metastatic thyroid cancer and that side-effects are minor.
The serum enzyme pattern, consisting of GOT, GPT, lactate dehydrogenase, gamma glutamyl transpeptidase and alkaline phosphatase, was investigated in 128 patients with sonographically verified liver metastases. Gamma glutamyl transpeptidase and alkaline phosphatase turned out to be the most sensitive enzymes, being elevated in 89% and 88%, respectively. The GOT was elevated in 45% GPT in 37.5% and lactate dehydrogenase in 56% of all cases. The enzyme elevation did not correlate with the degree of liver involvement. In conclusion, pathological serum enzyme patterns are useful for the detection and follow up of liver metastases. Normal serum enzyme levels do not rule out the presence of liver metastases.
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Increasing knowledge in pathophysiology of hormone-related malignant tumors of breast combined with successful development and application of endocrine-active drugs makes hormone-therapy more important in treatment of metastatic breast cancer. Basic connections, indications and clinical relevant treatments are briefly demonstrated.
25 patients with a malign neoplasia were treated with cytostatics. The endogenous creatinine clearance as a parameter of the kidney function was checked. Patients who had no side-effects, did not show important changes in kidney function immediately and 10 days after the treatment. Patients who had hyperemesis and diarrhoea showed an impairment, patients with a hyperkinetic reaction improvement of kidney function. General hyperhydration during a cytostatic treatment is not necessary, it can even be dangerous for patients with a hyperkinetic reaction.
Since 1973 several methods were described in the literature to prevent Doxorubicin induced alopecia. Besides the application of pressure scalp hypothermia gained increasing importance. Various modifications of scalp hypothermia were developed which are expensive and not easy in the handling so far. We are introducing a method in which a pneumatic cap is used for the application of ice on the scalp. With this method which is comperatively cheap and easy to be handled we got a protective effect against doxorubicin-induced hair loss which was at least as efficient as the current results with other methods referred in the literature.
In clinical oncology emergency situations are either manifestations of the underlying disease or effects of the treatment. The successful treatment of emergency situations is not only important in diseases in which cure is possible. It contributes also essentially to an optimal palliation for not curable disease states in oncology. Some special examples from the point of view of internal medicine are briefly discussed.
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Only between 0.5 and 1.2% of all breast cancers are found in men. Over the past 20 years 17 male breast cancers were treated in the University Clinic of Graz/Austria. Seven of these cases had localized disease and primary surgical treatment was performed; three out of the seven are still alive and show disease-free intervals of 2, 6 and 10 years, respectively. The metastatic cases were treated by various combinations of surgical treatment, radiotherapy, hormonal treatment and chemotherapy. Our results confirm the numerous communications in the literature that the therapeutic approach to male breast cancer is not essentially different to the management of female breast cancer at potentially curable stages. Primary orchidectomy still holds a dominant position in metastatic stages. Nevertheless, hormonal treatment with anti-oestrogens achieved an overall response rate of nearly 50%, which is comparable to the results with primary orchidectomy. Hence, this treatment is becoming of increasing importance as the primary form of treatment in hormone-sensitive metastatic male breast cancer.
The clinical usefulness of tumor scanning methods is discussed under the practical considerations of tumor screening, determination of tumor size and noninvasive tumor staging as well as diagnostic follow-up after therapy. Scintigraphy as a primary diagnostic tool is mainly restricted to suspicious enlargements of the thyroid gland whereas scintigraphy with 67Ga-citrate in Hodgkin's disease and bone scintigraphy with 99mTc-phosphates in tumors with tendencies to early bone metastases are widely used non-invasive diagnostic means for the evaluation of tumor propagation. Post therapy conversion of positive findings is of less predictive value than than persistence of a positive scan. Some results of the literature are discussed with our own experiences.