Vincristine,doxorubicin and mitomycin (VAM) in patients with advanced breast cancer previously treated with cyclophosphamide,methotrexate and fluorouracil (CMF)

Cancer Chemotherapy and Pharmacology - Thirty-six evaluable patients with advanced breast cancer who had failed prior CMF therapy [15 (42%) as adjuvant treatment and 21 (58%) for advanced disease]...     

Pharmacokinetics of vincristine in the cerebrospinal fluid of humans

Using a sensitive radioimmunoassay, concentrations of vincristine and its products were determined in cerebrospinal fluid (CSF) and corresponding blood samples from four patients with lymphoma and two patients with leukemia who had received i.v. bolus injection of 2 mg vincristine. Serial samples of CSF were withdrawn from a CSF reservoir in two patients during a 24-hr period following injection. The first time point after injection at which measurable levels of vincristine were detected in the CSF was 30 min; the concentrations were within the lower range of sensitivity of the assay and were 20- to 30-fold lower than were corresponding serum samples. Despite a prolonged terminal half-life of vincristine in the serum (14.4 to 37.5 hr) following i.v. bolus injection, concentrations of vincristine in the CSF ranged between undetectable within the limits of the assay and 1.1 X 10(-9) M during the 24-hr period of observation. The highest CSF concentration of vincristine (2.6 X 10(-9) M) has been observed in a patient receiving cranial irradiation for active meningeal lymphoma. No measurable levels of vincristine or its products were detected in spot samples of CSF from three patients. Penetration of vincristine and its products into the CSF of humans after i.v. bolus injection appears to be very poor and may account for the uncommon occurrence of central neurotoxicity following its clinical use.     

Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.

Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.     

Body composition during nutritional repletion of severely undernourished men.

Body composition was studied in severely undernourished adult male inhabitants of a rural area of Colombia to evaluate the extent and the time course of the changes occurring upon nutritional repletion. During a 45-day basal period on a low (26g/day) protein diet containing adequate calories, body fat depots increased significantly (mean +/- SD = +3.02 +/- 2.9 kg), and there was a significant decrease in cell hydration from 81.8 to 76.4% (-5.4 +/- 9.1%). Upon protein repletion (100 g/day), cell hydration decreased significantly to 71.4%, while body cell mass increased markedly (9.0 +/- 1.1 kg). During protein repletion, muscle cell mass increased significantly (+5.5 +/- 0.6 kg) and rapidly, while the increase in nonmuscle cells (+3.5 +/- 3.8 kg) and specifically in red cell mass lagged behind. With repletion, the changes in the absolute values for plasma volume (+0.4 +/- 0.13 liters) were significant, but those in extracellular fluid volume (-0.7 +/- 1.9 liters) were not. Thus, the major compositional changes observed occurred in the body fat and the body cell mass components; these occurred independently of each other.     

Assessment of Risks of Brodifacoum to Non-target Birds and Mammals in New Zealand

The risks to non-target birds and other wildlife from the use of vertebrate pesticides, including anticoagulant rodenticides, are determined to a significant extent by species' intrinsic susceptibility, and the toxicokinetics of the compounds used. Brodifacoum is highly toxic to birds and mammals. The acute toxicity of brodifacoum to birds in New Zealand varies from <1 mg/kg in pukeko (Porphyrio p. melanotus), the native swamp hen, to >20 mg/kg in the paradise shelduck (Tadorna variegata). Like other second-generation anticoagulants brodifacoum is strongly bound to vitamin K epoxide reductase and will persist, apparently for at least 6 months, in organs and tissue containing this enzyme, e.g., liver, kidney, and pancreas. The unique toxicokinetics of this class of compound exacerbates the risk of primary and secondary poisoning of non-target species. Vertebrate pest control programmes in New Zealand using bait containing brodifacoum have resulted in the primary and secondary poisoning and sub-lethal contamination of non-target species. These include native raptors, such as the Australasian harrier (Circus approximans) and morepork (Ninox novaeseelandiae), other native birds such as the pukeko, weka (Gallirallus australis), southern black-backed gull (Larus dominicanus), and kiwi (Apteryx spp.), and introduced mammals, including game animals. There are increasing numbers of reports worldwide of wildlife contamination and toxicosis after the use of second-generation anticoagulants. All pest control activities require careful risk-benefit assessment in view of their potential to cause adverse environmental impact. Monitoring of wildlife for pesticide residues will provide data that can be used to reduce the risk of anticoagulant bioaccumulation and mortality in non-target species.