Anti-cancer drugs
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Methylcholanthrene-induced sarcoma formation in mice was found to be effectively inhibited by the intraperitoneal injection of mistletoe extract (Iscador M). Induction of sarcoma and sarcoma-induced death were inhibited completely at a concentration of 1 mg Iscador/dose. ⋯ Mistletoe extract was also found to inhibit lung metastasis induced by B16F10 melanoma cells in mice. Simultaneous administration of the Viscum album extract inhibited lung nodule formation by 92.0% and produced a 71.3% increase in life span.
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The aim of this study was to analyse whether Viscum album (mistletoe; Isorel) modulates the tumour-host relationship and whether this might be a basic mechanism of the antitumorous activity of the drug. The effects of a single intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of Isorel reduced the size of the tumour and caused abundant tumour necrosis with inflammatory response, oedema and destruction of the malignant tissue. ⋯ Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to the cytotoxic activity of the lymphocytes than the control tumour cells, particularly in the presence of the plasma of mistletoe extract-treated mice. The plasma itself, however, did not show any cytotoxic activity. These results indicate that the antitumour activity of the mistletoe drug is due to a modulation of the tumour-host relationship, mediated by direct cytotoxicity of the drug to tumour cells and/or through a potentiation of immune response by certain, as yet unidentified, growth modifying humoral factors of the host.
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The Viscum album (mistletoe) preparation Isorel is able to destroy tumour cells and to modify immune reactivity against a particular antigen in normal and in tumour-bearing animals. CBA/HZgr mice and methylcholanthrene-induced fibrosarcoma were used in these studies. A single dose of Isorel M (140 mg/kg or 1400 mg/kg body weight) significantly increased the number of plaque forming cells if applied at the time of injection of sheep red blood cells or 1 day earlier. ⋯ However, according to plaque forming cell numbers, a prolonged application of Isorel was significantly immunosuppressive in normal mice and particularly in tumour-bearing mice. It should be mentioned that the doses of Isorel used in this experiment were much higher than generally used in cancer patients. In view of the immunomodulating effects of Isorel, the monitoring of the immune response of the patients treated with mistletoe preparations is to be recommended.
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Forty chemotherapy-naive patients receiving high-dose cisplatin were included in a pilot study of a combination of ondansetron plus metoclopramide as antiemetic therapy. Patients received ondansetron 16 mg plus metoclopramide 0.5 mg/kg in 250 cm3 of normal saline i.v. 15 min before cisplatin administration on day 1; then ondansetron 8 mg was given orally b.i.d. and metoclopramide 0.5 mg/kg was given intramuscularly t.i.d. for 4 days. This combination was given to all patients receiving the first cycle of chemotherapy. ⋯ Although this study was not prospectively carried out in a randomized fashion, the results are not suggestive of a possible positive effect of metoclopramide addition to ondansetron. On the other hand, these results stress the role that corticosteroids may play in the control of delayed emesis. Toxicity was predictable and the frequency of side-effects was in the range reported in other studies with ondansetron.
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Clinical Trial
Phase I and pharmacology study of intoplicine (RP 60475; NSC 645008), novel topoisomerase I and II inhibitor, in cancer patients.
Intoplicine (RP 60475F; NSC 645008) is a novel 7H-benzo[e]pyrido[4,3-b]indole derivative which interacts with both topoisomerases I and II. Because of its high activity in preclinical cancer models, original mechanism of action and acceptable toxicity profile, intoplicine was further evaluated in a phase I and pharmacology study. Thirty-three (33) patients (24 men and nine women) meeting standard phase I eligibility criteria were included: median age was 56 years, performance status 0-1 in 28 patients and 2 in five patients. ⋯ In conclusion, the phase II recommended dose of intoplicine is 270 mg/m2 administered as a 1 h i.v. infusion every 3 weeks. Plasma and blood pharmacokinetics were linear within the dose range studied. Potentially cytotoxic concentrations were reached at clinically achievable doses.