摘要:

The efficacy of combination treatment with actinomycin D (Act D), recombinant human tumor necrosis factor- α (TNF- α), and recombinant murine interferon-γ (IFN-γ) was examined on established MmB16 melanoma in mice. TNF-α alone had marginal effect in vitro on melanoma cells. However, when this cytokine was combined with either Act D or IFN-γ, synergistic cytostatic/ cytotoxic effects were observed. The highest cytotoxicity was demonstrated in cultures of melanoma cells in which all three agents together were added. In mice inoculated with 106 melanoma cells (into the footpad of the hind limb) and treated locally with Act D, TNF- α and IFN-γ, beneficial therapeutic effects were found. When initiated 1 week after tumor cell inoculation, the 7-day treatment with all these agents administered together at daily doses: 0.2 μg (Act D), 1 μg (TNF- α), and 200 U (IFN-γ) resulted in a significant delay of tumor progression in comparison to the therapy that included either Act D alone or TNF- α in combination with IFN-y. Side effects of such a treatment, both local and systemic, were negligible. The results of this study demonstrate that combination of regional chemotherapy (actinomycin D) and immunotherapy (TNF- α /IFN-γ) may display higher efficacy than either treatment alone and may increase therapeutic index without augmenting toxic effects.

ISSN:0030-2414    

DOI:10.1159/000227531

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Cyclophosphamide induces moderate to severe emesis. The severity of emesis is dependent on the dose of cyclophosphamide and on the addition of other cytotoxic drugs. A review of the literature dividing studies according to the dose of cyclophosphamide and the specific cytotoxic combination shows that ondansetron plus dexamethasone provides optimal antiemetic therapy in patients receiving standard or high-dose cyclophosphamide ( ≥450 mg/m2). These studies also show that it is important to give antiemetic therapy to cover the prolonged duration emesis and nausea induced by these regimens, e.g. intravenous CMF/(F)AC/(F)EC. For continuous ‘oral’ (low-dose) CMF chemotherapy, oral ondansetron or oral metoclopramide plus intravenous (or possibly oral) dexamethasone are effective antiemetic ther

ISSN:0030-2414    

DOI:10.1159/000227638

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This retrospective study compares the results obtained in 56 children with medulloblastoma treated with two different protocols at our center between 1975 and 1990. Since 1985 we have been enrolled in the medulloblastoma SIOP II protocol in which we have entered 27 patients. These patients form the SIOP group (SG) and the 29 children treated before 1985, the historical group (HG). When the two groups were compared for age and sex distribution, no differences were found; however, prognostic factors were worse in the HG than in SG: 21 versus 15 T3–T4 and 13 versus 8 high-risk, respectively. The relapse rate was 63% for the HG and 39% for the SG. Five-year disease-free survival was 31% for the HG and 56% for the SG (p = 0.037). Five-year survival was 52 and 70%, respectively (p = 0.055). When SG and HG were compared by stratifying for tumor size, surgical resection and the risk variable, better disease-free survival was obtained in SG than in HG. In a multivariate analysis, the HG and the high-risk proved to be variable independent predictors of poor survival. We observe an increase in survival in our patients with medulloblastom

ISSN:0030-2414    

DOI:10.1159/000227532

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This paper describes the only published study to date which prospectively evaluates the efficacy of a 5-HT3 receptor antagonist over repeated courses of cyclophosphamide chemotherapy. The combination of ondansetron and dexa-methasone was significantly superior to metoclopramide and dexamethasone over 6 courses of chemotherapy given for the treatment of breast cancer. Importantly, patients given ondansetron benefited from a superior quality of life over the six courses of treatment. A Markov chain statistical model has been applied to these data. This model assumes that the results over subsequent courses is dependent on the efficacy of the anti-emetic therapy and the results obtained during the previous course of chemotherapy. This model successfully predicts the actual results obtained in the clinical study. Using this model it is possible to hypothesise on the results obtained following different treatment strategies. These data emphasise that it is important to give optimal anti-emetic therapy from the first course of chemotherapy as this will facilitate good control during subsequent courses.

ISSN:0030-2414    

DOI:10.1159/000227639

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The prognosis of brain glioblastoma is still very poor and the median survival time is generally less than 6 months. At present, no chemotherapy has appeared to influence its prognosis. On the other hand, recent advances in brain tumor biology have suggested that brain tumor growth is at least in part under a neuroendocrine control, mainly realized by opioid peptides and pineal substances. On this basis, we evaluated the influence of a concomitant administration of the pineal hormone melatonin (MLT) in patients with glioblastoma treated with radical or adjuvant radiotherapy (RT). The study included 30 patients with glioblastoma, who were randomized to receive RT alone (60 Gy) or RT plus MLT (20 mg/daily orally) until disease progression. Both the survival curve and the percent of survival at 1 year were significantly higher in patients treated with RT plus MLT than in those receiving RT alone (6/14 vs. 1/16). Moreover, RT or steroid therapy-related toxicities were lower in patients concomitantly treated with MLT. This preliminary study suggests that a radioneuroendocrine approach with RT plus the pineal hormone MLT may prolong the survival time and improve the quality of life of patients affected by glioblastoma.

ISSN:0030-2414    

DOI:10.1159/000227533

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Carboplatin has proven efficacy in the treatment of ovarian cancer and has been proven to be less toxic compared to the parent compound cisplatin. Nevertheless, emesis is still a major problem associated with carboplatin-containing chemotherapy. Several investigators have focussed on the understanding of the pathophysiology and pattern of cisplatin-induced emesis. Data describing both the pathomechanisms and pattern of carboplatin-induced emesis are still lacking. This paper combines data from the literature with our own experience with the pattern and control of carboplatin-induced emesis, and presents data contributing to the understanding of the underlying pathomechanisms. Carboplatin induces a significant increase in urinary 5-HIAA excretion, the main metabolite of serotonin. 5-HIAA excretion levels remain elevated over 3 days following chemotherapy. Carboplatin-induced emesis is observed in about 40% of patients despite anti-emetic prophylaxis with 5-HT3 24 h after chemotherapy) is a major problem associated with carboplatin therapy. Description of the pattern of emesis as ‘prolonged emesis’ seems to be appropriate. 5-HT3 receptor antagonists such as ondansetron seem to be efficacious both in the control of acute and prolonged emesis following carboplatin chemotherapy, but randomly controlled data comparing ondansetron with other anti-emetic regimens have not yet been published. Univariate analysis reveals gender and combination therapy containing carboplatin and cyclophosphamide and/or anthracyclines as risk factors for e

ISSN:0030-2414    

DOI:10.1159/000227640

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

114 patients received a standard and 75 patients an extended resection of ductal pancreatic carcinoma at the Hanover Medical School, Germany, from 1971 until 1993. Standard pancreatic resections were combined with vascular resection and reconstruction in 46 and additional organ resections in 45 cases. Vascular resections affected the mesentericoportal vein in 37, the common hepatic in 10 and the superior mesenteric artery in 7 cases. Pancreas resections were combined with total gastrectomy in 23, partial colectomy in 17, hemihepatectomy in 14, adrenalectomy in 8 and nephrectomy in 5 patients. Curative resections could be accomplished in 86% of patients without and 81% with extended resections. Additional vascular resections neither increased the operative risk nor deteriorated the long-term prognosis after resection. Additional organ resections, however, significantly increased the risk of lethality and impaired the long-term prognosis. Especially resections of synchronous hepatic metastases and colectomies were associated with a poor survival probability.

ISSN:0030-2414    

DOI:10.1159/000227534

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A number of non-cisplatin cytotoxic regimens induce moderate to severe nausea and emesis. Moreover, the majority of these regimens are given to outpatients where an effective, well-tolerated anti-emetic therapy is particularly important to maintain patients’ well-being. This review focuses on the management of nausea and emesis induced by non-cisplatin chemotherapy particularly regimens that do not contain cyclophosphamide or carboplatin, as these are reviewed elsewhere in this volume. For patients receiving highly emetogenic cytotoxic therapy such as dacarbazine, total body irradiation or hemi-body irradiation, a 5-HT3 receptor antagonist plus a corticosteroid may provide optimal control of emesis and nausea. High-dose single-fraction and fractionated radiotherapy to the upper abdomen induces moderate emesis. Traditional anti-emetics prevent emesis in approximately 50% of patients; 5-HT3 receptor antagonists provide a more effective anti-emetic therapy for these patients. Studies evaluating anti-emetics in specific chemotherapy regimens will give clear guidelines for the management of emesis in different patient population

ISSN:0030-2414    

DOI:10.1159/000227641

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Background: The association of 5-fluorouracil (5-FU) and leucovorin is currently the most used combination in the treatment of advanced gastrointestinal neoplasms. Doxifluridine (d-FUR) is a fluoropyrimidine derivative that is converted into 5-FU inside tumor cells, where it is selectively cytotoxic. The oral administration of dFUR has been extensively investigated in colorectal carcinoma, and has been proven to be active and well tolerated. The purpose of this study was to test the effectiveness of the oral combination with dFUR plus l-leucovorin in gastric and pancreatic cancer patients. Methods: A total of 50 cases were treated with l-leucovorin 25 mg, followed 2 h later by d-FUR 1,200 mg/m2 for 5 days; the cycles were repeated every 10 days. The regimen was given for a maximum of 36 cycles or until disease progression. Twenty-six patients had gastric cancer (all of whom were pretreated with polychemothera-py) and 24 had advanced pancreatic carcinoma. Results: Objective responses were obtained in 4 (15%; 95% CI 1–29) patients with gastric cancer, and in 1 (4%) with pancreatic cancer. The median response duration was 4 months. All of the responses were seen in patients previously treated with 5-FU-containing regimens. The median survival in gastric cancer patients was 7 months. Toxicity was moderate: WHO grade III and IV diarrhea was observed in 14% of the cases. Conclusions: This study indicates the efficacy of oral d-FUR plus l-leucovorin as palliative treatment in gastric cancer patients. The results in pancreatic carcinoma are disappointing but are in line with the published data relating to fluoropyrimidines.

ISSN:0030-2414    

DOI:10.1159/000227535

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A survey by Coates and co-workers in 1983 revealed that patients ranked nausea and vomiting as the most distressing side effects of chemotherapy. In the last decade the use of high-dose metoclopramide and, especially, the introduction of the 5-HT3 receptor antagonists, have been major leaps forward in the control of chemotherapy-induced emesis. Nevertheless, since patients still consider nausea and vomiting to be the most distressing side effect of their chemotherapy there is clearly a need for further improvements. Acute emesis, which is the topic of this review, can now be controlled in the majority of patients during their first course of chemotherapy. Future focus should be on better control of emesis during subsequent courses of chemotherapy as well as on better control of delayed emesis.

ISSN:0030-2414    

DOI:10.1159/000227642

出版商:S. Karger AG    

年代:1996

数据来源: Karger