Michael J. Barnett

EVA treatment for recurrent or unresponsive Hodgkin's disease

SummaryNineteen patients with recurrent or unresponsive Hodgkins disease who had previously received combination chemotherapy comprising mustine or chlorambucil with vinblastine, prednisolone and procarbazine (MVPP or ChlVPP), were treated with a combination of etoposide, vincristine and adriamycin (EVA). Clinical remission (complete, CR + good partial, GPR) was achieved in eleven of the nineteen patients (58%). The remission rate was similar for patients who had previously responded well to chemotherapy and for those who had previously been poorly responsive. Six patients have relapsed between 3 and 5 months after completion of therapy. The remainder continue in remission, two without further therapy at 7 and 8 months, respectively, and three having had additional radiotherapy while in remission. Myelosuppression was the most important toxicity, but in general this was manageable. These results suggest that EVA may be non-cross-resistant with MVPP and ChlVPP and that it is of potential value in combination chemotherapy for previously untreated patients, even though it is unlikely to be curative when treatment with either MVPP or ChlVPP has failed.

The effect of food on the oral administration of 6-mercaptopurine

SummaryThe effect of food on the bioavailability of 6-mercaptopurine (6-MP) has been investigated. Seven patients were studied on two separate occasions. On the first occasion 6-MP was administered p. o. after an overnight fast and on the second, 15 min after a standard breakfast. 6-MP concentrations were determined by high-performance liquid chromatography. Variable plasma drug levels were observed between individual subjects in the fasting state. The peak levels of 6-MP were lower and took longer to be achieved following administration after a standard breakfast than after an overnight fast. In two subjects levels were undetectable (<20 ng/ml). In view of these observations it is suggested that 6-MP should be administered before food if maximum blood levels are to be achieved.

Treatment of acute leukaemia with m-AMSA in combination with cytosine arabinoside

SummaryA series of 46 patients with acute leukaemia were treated with amsacrine (m-AMSA) and cytosine arabinoside (ara-C). Complete remission (CR) was achieved in 15 of 38 (40%) patients with acute myelogenous leukaemia (AML) and 4 of 8 (50%) patients with acute lymphoblastic leukaemia (ALL). The CR rate was significantly higher (P(0.05) for the younger, previously treated patients with AML (9/16) than for the older previously untreated ones (6/22), because of higher treatment mortality in the latter group.Myelosuppression was prolonged and profound. Major nonhaematological toxicity affected the gastrointestinal tract (nausea, vomiting, mucositis, bleeding and ileus associated with severe diarrhoea). Many patients also developed reversible hepatic dysfunction and two elderly patients died of cardiac arrhythmia.Further trials of this combination are justified in patients with relapsed or resistant leukaemia, but for older patients dose reduction is recommended.

The bioavailability of oral intermediate-dose methotrexate

SummaryThe oral bioavailability of methotrexate is variable and may be dose-dependent. The absorption of ‘interval’ oral methotrexate, which is given between cycles of chemotherapy, is unknown.The bioavailability of oral methotrexate has been studied in eight patients, acting as their own controls, to assess the effect of subdivision of the dose, the formulation, and the timing of the methotrexate within the chemotherapy cycle.The mean bioavailability for all the oral methods of administration was 28.2%±3.7% compared with the same dose given IV. Absorption was uninfluenced by subdivision of the dose, liquid or tablet formulation, or administration on day 1 or day 10 of the chemotherapy cycle.

A phase II study of high-dose cytosine arabinoside in the treatment of acute leukaemia in adults

SummaryTwenty-seven adults with refractory or recurrent acute leukaemia were treated with cytosine arabinoside (ara-C) 2 g/m2 infused over 3 h, every 12 h for 6 days, either alone (regimen A) or with vincristine and prednisolone (regimen B). Complete remission was achieved in 9/18 patients (5/12 regimen A, 4/6 regimen B) with acute lymphoblastic leukaemia (ALL), 1/7 patients (1/5 regimen A) with lymphoid blast crisis of chronic myeloid leukaemia (CML.LBC) and 1/2 patients (1/1 regimen B) with acute undifferentiated leukaemia (AUL). A further 5 patients (4 regimen A, 1 regimen B) with ALL, 4 patients (3 regimen A, 1 regimen B) with CML.LBC and 1 patient (regimen A) with AUL showed evidence of significant response. These results confirm the activity of high-dose ara-C in acute non-myelogenous leukaemia and suggest that it might be used with benefit to intensify the initial treatment of ‘poor-risk’ ALL.

Treatment of myeloblastic sarcoma in the sacral canal with high-dose cytosine arabinoside

SummaryWe report a case of recurrent myeloblastic sarcoma in the sacral canal following local radiotherapy, treated effectively with high-dose cytosine arabinoside.