Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors

Purpose

Omacetaxine mepesuccinate is a first-in-class cephalotaxine demonstrating clinical activity in chronic myeloid leukemia. A subcutaneous (SC) formulation demonstrated efficacy and safety in phase 1/2 trials in patients previously treated with ≥1 tyrosine kinase inhibitor. This study assessed pharmacokinetics and safety of SC omacetaxine in patients with advanced cancers.

Methods

Omacetaxine 1.25 mg/m² SC was administered BID, days 1–14 every 28 days for 2 cycles, until disease progression or unacceptable toxicity. Blood and urine were collected to measure omacetaxine concentrations and inactive metabolites. Adverse events, including QT interval prolongation, were recorded. Tumor response was assessed at cycle 2 completion.

Results

Pharmacokinetic parameters were estimated from cycle 1, day 1 data in 21 patients with solid tumors or hematologic malignancies and cycle 1, day 11 data in 10 patients. Omacetaxine was rapidly absorbed, with mean peak plasma concentrations observed within 1 h, and widely distributed, as evidenced by an apparent volume of distribution of 126.8 L/m². Plasma concentration versus time data demonstrated biexponential decay; mean steady-state terminal half-life was 7 h. Concentrations of inactive metabolites 4′-DMHHT and cephalotaxine were approximately 10 % of omacetaxine and undetectable in most patients, respectively. Urinary excretion of unchanged omacetaxine accounted for <15 % of the dose. Grade 3/4 drug-related adverse events included thrombocytopenia (48 %) and neutropenia (33 %). Two grade 2 increases in QTc interval (>470 ms) were observed and were not correlated with omacetaxine plasma concentration. No objective responses were observed.

Conclusions

Omacetaxine is well absorbed after SC administration. Therapeutic plasma concentrations were achieved with 1.25 mg/m² BID, supporting clinical development of this dose and schedule.     

Impact of opening an acute palliative care unit on administrative outcomes for a general oncology ward

BACKGROUND.

Acute palliative care units (APCUs) are gaining popularity in tertiary care centers. In this study, the authors examined the impact of opening an APCU on administrative outcomes for a general oncology ward (GOW) at a comprehensive cancer center.

METHODS.

The GOW database was reviewed for 3 periods: June 2000 through May 2002 (before the APCU opened), June 2002 through May 2004 (transitional period, including APCU opening in a temporary location), and June 2004 through May 2006 (after opening of the APCU). Data were extracted on demographics, reasons for admission, admission type, waiting time for admission, length of stay (LOS), overstay (>2 days over expected LOS), death rate, and discharge destination. Linear regression analysis and the Cochran‐Armitage test were used for data analysis.

RESULTS.

There were 5340 admissions: The median patient age was 60 years, and 55% of patients were women. The most common primary cancers were head and neck (22%), gynecologic (21%), gastrointestinal (13%), and lung (12%). There were significant trends on the GOW in decreased admissions for palliative care (12.2%, 9.6%, and 7.9%, respectively, for the 3 periods; P < .0001), fewer inpatient deaths (11.4%, 8.6%, and 6.1%, respectively; P < .0001), and fewer patients with prolonged waits for a bed on a palliative care unit (3.4%, 3%, and 1.7%, respectively; P = .002). Admissions increased for interventions (10.4%, 17.3%, and 22.5%, respectively, for the 3 periods; P < .0001) and for chemotherapy (6.8%, 6.6%, and 9.7%, respectively; P = .001).

CONCLUSIONS.

After the opening of an APCU at the authors' cancer center, the GOW experienced a decrease in administrative endpoints related to palliative and end‐of‐life care and an increase in endpoints related to cancer‐directed interventions. Prospective studies with clinical endpoints will be required to determine whether this specialization of inpatient care improves quality of life, quality of death, and psychosocial well being. Cancer 2008. © 2008 American Cancer Society.     

A preliminary study of sex-related differences in prolactin responses to dopamine blockade and insulin hypoglycemia and in penfluridol plasma levels in schizophrenic patients

Twelve healthy chronic schizophrenic patients were treated with the long-acting oral dopamine (DA) receptor blocker penfluridol (100 mg orally) for 6 weeks. Plasma prolactin (PRL) levels were measured during insulin-tolerance tests (ITT) performed at the end of the drug-free period (7-10 days) and during weeks 1 and 6 of penfluridol treatment. Simultaneous PRL and penfluridol plasma levels were determined just prior to, and at 8, 72 and 120 h after penfluridol administration during weeks 1, 5, and 6. During penfluridol treatment women (N = 4) had a greater increase in their maximal PRL increments after ITT as compared to the men (N = 8). Analyses of (peak) plasma penfluridol and PRL concentrations 8 h after penfluridol administration revealed a trend towards lower plasma penfluridol levels during weeks 5 and 6 and significantly higher PRL levels in women compared to men during weeks 1 (P less than 0.01), 5 (P less than 0.02), and 6 (P less than 0.02). The consistent sex-related differences in the PRL responses to DA blockade, and to insulin-induced hypoglycemia and in the penfluridol plasma levels in our study support the view that sex-related changes need to be considered not only in the hormonal responses to various pharmacological agents, but also in the assessment of the plasma levels of these drugs.     

Determinants of quality of life in patients with advanced cancer

Purpose  

Improving health-related quality of life (HRQL) is the main goal of palliative care and an important outcome for oncology trials. This study examines medical and sociodemographic determinants of HRQL in outpatients with advanced cancer.     

Pulse polio immunization in district Panipat: A process evaluation

Objective  

To evaluate all steps of pulse polio immunization on special sub national immunization day.     

Impact of mass supplementation of Vitamin A

Objective To study the impact of mass supplementation of Vitamin A solution on morbidity due to diarrhea, Acute respiratory infection (ARI) and xerophthalmia. Methods The two rounds of age specific mass distribution of Vitamin A solution were undertaken during January 2000 and December 2000 respectively covering 27642 (98.7%) and 31762 (88.0%) children respectively out of total beneficiaries in two round of PPI in Chandigarh. A random sample of 276 children from intervention area and 252 children from control area in the age group of 1–5 yr were followed up on monthly basis for morbidity pattern for a period of nine mth. The morbidity pattern for intervention and control area children was compared to see the impact of mass supplementation of Vitamin A solution. Results The average annual episodes of diarrhea in intervention children were lower (3.9 per yr) as compared to control children (5.2 per yr) although difference was not statistically significant (P>0.05) except in initial month. The average annual episodes of ARI in intervention children were lower (5.1 per yr) as compared to Control children (6.0 per yr) although difference was not significant (P>0.05) except in initial first mth. There was significant decline in vitamin A deficiency (VAD) as no case of Bitot’s spot was found in intervention children as compared to control children where the prevalence of Bitot’s spot ranged from 4.3–5.08% during different visits. The mortality rate was found to be higher in control children with a death rate of 8 per 1000 children during the study period as compared to intervention children where no death was recorded. Conclusion It is concluded that mass supplementation of vitamin A led to significant reduction in xerophthalmia and decline in mortality in the intervention area as compared to control area.