Cancer patients receiving cytotoxic chemotherapy often become anaemic and may require blood transfusions. A large-scale audit of patients with a variety of solid tumours receiving chemotherapy at 28 specialist centers throughout the UK was undertaken to quantify the problem. Data were available from 2719 patients receiving 3206 courses of cytotoxic chemotherapy for tumours of the breast (878), ovary (856), lung (772) or testis (213). Their mean age was 55 years (range 16–87). Overall, 33% of patients required at least one blood transfusion but the proportion varied from 19% for breast cancer to 43% for lung. Sixteen per cent of patients required more than one transfusion (7% for breast, 22% in lung). The mean proportion of patients with Hb < 11 g dl−1rose over the course of chemotherapy from 17% before the first cycle, to 38% by the sixth, despite transfusion in 33% of patients. Of the patients receiving transfusions, 25% required an inpatient admission and overnight stay. The most common symptoms reported at the time of transfusion were lethargy, tiredness and breathlessness. Further research is needed to evaluate the role of blood transfusions in patients receiving cytotoxic chemotherapy. © 2000 Cancer Research Campaign

Nolatrexed can be safely administered to patients at a dose of 800 mg/m2/d over 5 days by continuous intravenous infusion and this schedule is associated with antitumor effects. The phase II evaluation of nolatrexed is ongoing.

Summary The aim of this phase study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-'min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated with paclitaxel followed by a 30-min infusion of carboplatin. Paclitaxel dose was escalated from 150 mg m-2 to 225 mg m-2 in cohorts of three patients. Carboplatin dose was based on renal function. Pharmacokinetic studies were performed in nine patients (at least two at each dose level). A total of 66 courses were evaluable for assessment. Grade 3 or 4 neutropenia was seen in 70% of the courses, however hospitalization was not required. Grade 3 or 4 thrombocytopenia occurred in 24% of the courses. Alopecia, myalgia and peripheral neuropathy were common but rarely severe. The pharmacokinetics of paclitaxel was non-linear and did not appear to be influenced by co-administration of carboplatin. The AUC of carboplatin was 7.0±1.4 mg ml-' min, indicating that there was no pharmacokinetic interaction. The combination of carboplatin and paclitaxel may be administered as first-line treatment for advanced ovarian cancer. Although myelosuppression is the dose-limiting toxicity of the component drugs, the severity of thrombocytopenia was less than anticipated. The results of this study, with only a small number of patients, need to be confirmed in future investigations.

Lometrexol is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Extensive experimental and limited clinical data have shown that lometrexol has activity against tumours which are refractory to other drugs, notably methotrexate. However, the initial clinical development of lometrexol was curtailed because of severe and cumulative antiproliferative toxicities. Preclinical murine studies demonstrated that the toxicity of lometrexol can be prevented by low dose folic acid administration, i.e. for 7 days prior to and 7 days following a single bolus dose. This observation prompted a Phase I clinical study of lometrexol given with folic acid supplementation which has confirmed that the toxicity of lometrexol can be markedly reduced by folic acid supplementation. Thrombocytopenia and mucositis were the major toxicities. There was no clear relationship between clinical toxicity and the extent of plasma folate elevation. Associated studies demonstrated that lometrexol plasma pharmacokinetics were not altered by folic acid administration indicating that supplementation is unlikely to reduce toxicity by enhancing lometrexol plasma clearance. The work described in this report has identified for the first time a clinically acceptable schedule for the administration of a GARFT inhibitor. This information will facilitate the future evaluation of this class of compounds in cancer therapy.

No abstract