No abstract

PEG+E is effective in the clinical management of constipation in an institutional setting. Furthermore, long-term intensive therapy with PEG+E was not associated with adverse effects on body weight or blood biochemistry values. Although the time periods over which the economic data and the efficacy and safety data were collected did not directly correspond, this study indicates that use of PEG+E in the management of constipation in people with severe intellectual disability may be cost-effective, reducing hospital laxative costs.

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon ␣-2b (IFN-␣2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-␣-2b (3 MU/m 2 /day 1st week and then 5 MU/m 2 /day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.

Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m 2 (6-hr intravenous [IV]) and 3 mg/m 2 IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m 2 (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m 2 with doses ranging from 12-18 mg/m 2 IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m 2 . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m 2 . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.