ISSN:0378-584X    

DOI:10.1159/000218214

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218215

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218319

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: The overall prognosis of node-negative breast cancer patients is better than that of patients with metastatic nodes. Nevertheless, 25–30% of node-negative patients later on develop metastatic cancer. Definition of prognostic factors for better selection of those patients who would benefit from adjuvant systemic therapy is, therefore, of great importance. Patients andMethods: In 194 patients with operable breast cancer and negative lymph node status, the importance of different clinical and histological features with respect to survival was retrospectively and double-blindly investigated. Life table analysis, Cox regression analysis, and multivariate discrimination analysis were used for statistical evaluation. Results: Life table analysis showed the highly significant importance of vascular invasion (blood and lymph vessels) in comparison with grading for 10-year survival. Cox regression analysis showed vascular invasion as the only significant factor for long-terfn survival as did multivariate discrimination analysis which recognized menopause status and the paracortical zone of regional lymph nodes in 2nd and 3rd position of significance. Conclusions: Vascular invasion is a factor of great importance for long-term survival of node-negative breast cancer patients. It should be determined in a clinical study, whether the risk of metastatic cancer in patients with vascular invasion can be diminished by adjuvant systemic therapy and whether the prognosis of these patients can thus be improve

ISSN:0378-584X    

DOI:10.1159/000218216

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: Treatment results in advanced colorectal cancer (CC) remain unsatis-factory and palliative, with 5-fluorouracil with or without calcium folinate being the only drug able to induce clinically acceptable response rates.Patients and Methods: A clinical phase II study is presented with an oral formulationof the phospholipid derivative miltefosine (MIL) in patients with advanced colorec-tal cancer. Patients were stratified according to pretreatment. Only non-pretreatedor pretreated patients who had received 5-fluorouracil with or without calcium folinate were accepted. MIL was given as capsule twice daily at a single dose of 50 mg for the 1st week with dose escalation to 150 mg (50 mg × 3) in the 2nd week and subsequently in case of good tolerability. Nine weeks were considered the minimal duration of treatment.Results: 54 patients were evaluable for toxicity and 44 were evaluable for response. A short-lived partial response was observed in one pretreated female patient with multiple lung lesions, a ‘no change’ status in 14 patients, including 8 nonpretreated patients (42%) and 6 pretreated patients (24%). Side effects were distinct, with loss of appetite, nausea and vomiting up to grade 4 WHO and weight loss of more than 5 kg in 3 months in a considerable number of patients. Furthermore, an increase of leukocyte and platelet counts was observed during the first 2 months of treatment. Conclusion: Oral MIL is considerably toxic and has only marginal therapeutic activity in patients with colorectal ca

ISSN:0378-584X    

DOI:10.1159/000218217

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: Hyperthermic isolated limb perfusion (HILP) is a standardized technique for treatment of malignant melanoma (MM) and soft-tissue sarcoma (SA). Doxorubicin (DOX) has proved to be effective in HILP chemotherapy. DOX levels in the perfusate can be influenced by various factors. Particularly heparin-induced precipitation and adhesion to plastics have been discussed to modify bioavailability of the drug to the treated tumor. Peripheal DOX pharmacokinetics in the perfusate were investigated to clarify if DOX levels are compromised by the artificial conditions during HILP. Data should also contribute to a further improvisation of DOX dosage during the procedure. Material and Methods: DOX pharmacokinetics were analyzed in 7 patients with MM and SA during clinical HILP of the upper/lower extremity after bolus administration of 10 or 20 mg DOX. Influence of high heparin dosage (10/25 IU/ml heparin) on DOX pharmacokinetics and adhesion to plastics was additionally evaluated during experimental perfusate recirculation without patient contact. For the detection and quantification of DOX and metabolites a high-performance liquid chromatography assay was used. Results: All patients had measurable values of DOX during the total perfusion period. Metabolites, particularly the 7-deoxyaglycones, could be detected in low concentrations. DOXol is the major metabolite of DOX in the perfusate. This implicates that an aldo-keto-reductase, which is responsible for this metabolism, must be present in peripheral tissues. Mean half-life of DOX was 27.3 + 5,6 min, mean plasma clearance was 77.8 + 41.6 ml/min. Peripheral DOX metabolism appeared to be 10-fold reduced, when compared with the systemic metabolism. i We conclude that the continuous decrease of the DOX perfusate concentration during clinical HILP seems to be mostly a function of DOX tissue absorption. This is supported by the finding that neither relevant heparin-induced DOX precipitation nor a significant loss due to adhesion to plastics was noted in the experimental setting.

ISSN:0378-584X    

DOI:10.1159/000218218

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: Retinoic acid, the intracellular metabolite of vitamin A, induces differentiation in glioblastoma cultures and recognizes nuclear retinoic acid (RA) receptors in human glial cells. Its degradation can be inhibited by the oral steroid synthesis modulator liarozole or R75251 (5-[(3-chlorophenyl) (lH-imidazole-l-yl)methyl]-lH-benzimidazole HC1). Measured by 3H-thymidine incorporation, liarozole also exhibits an intrinsic attenuating effect on glioblastoma growth in vitro. Patients and Method: Ten patients with primary malignant brain tumors have entered an open oral therapeutic pilot study with 13-cis-retinoic acid (isotre-tinoinINN; Roaccutan® Roche) and the catabolic inhibitor liarozole. Results: Side effects such as cheilitis, conjunctivitis, and desquamation dose-depend-ently correlated with plasma levels and could be regularly used for dose adjustments. The combined therapy produced and maintained elevated plasma concentrations and clinical retinoid effects with fractions of formerly necessary 13-cis-RA doses. In vivo, 75-150 mg liarozole combined with 5-20 mg 13-cis-RA daily increased plasma 13-cis-RA and 4-oxo-13-cis-RA levels more than threefold. Long-term all-trans-RA therapy without liarozole leads to a progressive downregulation of plasma RA levels. Such a decrease may be prevented by combining all-trans-RA with its catabolic inhibitor liarozole (Janssen). Conclusion: First clinical experience recommends liarozole for either 13-cis-or all-trans RA therapy in retinoid-sensitive malignancies such as neuro-ectodermal glioma or acute promyelocytic leukemia

ISSN:0378-584X    

DOI:10.1159/000218219

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: Ciclosporin A (CS-A) is a powerful immunosuppressive agent, isolated from the fungus Tolypocladium inflatum Gams. The value of CS-A in experimental oncology is at present not clear. Studies on xenogeneic tumor transplantation, on the reversal of cytostatic resistance in various tumor models, and on the combination of CS-A with different other cytostatic drugs have been published. Materials and Methods: The 6-day subrenal capsule assay (SRCA) was used. A murine reticulum cell sarcoma was transplanted under the renal capsule of female BlmNMRI mice. Different doses of CS-A (100, 80, 60, 40, and 10 mg/kg) were administered on 6 consecutive days both intraperitoneally and subcutaneously. Tumor size, body weight reduction, and mortality were evaluated.Results: The data demonstrate a significant cytostatic effect of CS-A in the murine reticulum cell sarcoma both after subcutaneous and intraperitoneal administration of CS-A at different doses. A dose-dependent tumor size reduction was found only in the subcutaneously treated animals. The toxicity, measured by body weight reduction, was also significantly higher in the subcutaneously treated animals, but the mortality was higher in the animals treated intraperitoneally with CS-A. Histologic eval-uation showed a reduction of the mitotic activity in all treated versus control groups.Conclusions: The results suggest that CS-A has a cytostatic effect in the murine reticulum cell sarcoma RS-180, transplanted under the subrenal capsule of syngeneic female BlmNMRI mice for 6 days, which is combined with a decrease in tumor size. Histologically, a reduction of mitosis in the groups treated with CS-A was found.

ISSN:0378-584X    

DOI:10.1159/000218220

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: The single-agent activity of the vinca alkaloid vinorelbine (Navel-bine®) in patients with relapsed or refractory nonseminomatous germ cell tumors was evaluated. Patients and Methods: Seven heavily pretreated patients received weekly an infusion (30 min) of vinorelbine at a dose of 30 mg/m2. Results: No responses (complete and partial remissions or no change) were achieved. We observed myelotoxicity with grade 3 leukopenia in 4 patients and grade 3 throm-bocytopenia in 2. No neurotoxicity was noted. Two patients had skin reactions at the site of infusion. Conclusions: Due to slow recruitment of patients, this phase II study has been terminated early. No role for vinorelbine was found in this patient group with an extremely unfavorable prognosis. The use of vinorelbine in combination regimens remains an issue of investigation

ISSN:0378-584X    

DOI:10.1159/000218221

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger

摘要:

Background: Antineoplastic chemotherapy may interfere with a positive hepatitis B surface antigen state in patients with hematologic neoplasias. Exacerbation of hepatitis can cause fatal delay in the treatment of malignant disorders. Introduction of interferon as a newer treatment approach in hepatitis B C as well as in non-Hodgkin lymphomas offers an alternative in this difficult clinical situation. Methods Results: We report on 2 patients with IgA plasmocytoma centro-cytic-centroblastic non-Hodgkin lymphoma in advanced disease stage who experienced exacerbation of hepatitis B while undergoing chemotherapy for their malignant disease. Follow-up of clinical disease biochemical markers of hepatitis including serology tumor marker study are outlined. With interferon therapy virus elimination was successful in the patient with centrocytic-centroblastic non-Hodgkin lymphomaallowing continuation of chemotherapy. Stable remission with minimal residual disease was reached. In case of IgA plasmocytoma a normalization of biochemical markers of hepatitis though persistent hepatitis B viremia was noticed. Also multiple myeloma was progressive under chemotherapy. Conclusions: Subtle serologic screening for hepatitis B virus infection in treatment of malignant hematologic disorders is recommendableprophylactic treatment of hepatitis B surface antigen carriers with interferon has to be considered. Initial control of malignant disease may be a good prognostic factor for successful virus elimination in case of exacerbation of hepatitis.

ISSN:0378-584X    

DOI:10.1159/000218222

出版商:S. Karger GmbH    

年代:1993

数据来源: Karger