Relationship between hematotoxicity and serum albumin level in the treatment of head and neck cancers with concurrent chemoradiotherapy using cisplatin.

OBJECTIVE: Patients with locally advanced head and neck cancer were treated with concurrent chemoradiotherapy using three courses of cisplatin. However, many patients were unable to complete the scheduled cisplatin treatment due to adverse effects. The objective of this study was to retrospectively elucidate the source of the low completion rate of cisplatin courses. METHODS: Between November 2007 and 28 May 2010, patients with head and neck cancer were treated with curative intent according to the concurrent chemoradiotherapy protocol (66-70 Gy at 2 Gy/day with cisplatin 80 mg/m(2) on Days 1, 22 and 43). Treatment courses, hematological data and other parameters were investigated, and the treatment completion rates and reasons for treatment failure were analyzed. RESULTS: Among the 28 patients, cisplatin was administered during the period of radiotherapy a total of 3 times in 9 (32%) patients, 2 times in 15 (54%) patients and only 1 time in 4 (14%) patients. Multiple regression analysis of the development of neutropenia at 3 weeks after the first cisplatin administration revealed that the serum albumin level was a significant explanatory variable (R(2)= 0.664, ß = 0.517, P< 0.01). Pearson's product-moment correlation coefficient showed a strong correlation between the serum albumin level and the neutrophil count after 3 weeks (r = 0.605, P< 0.01). CONCLUSIONS: The treatment completion rate by this protocol was low in head and neck cancer patients even when the cisplatin dose was reduced to 80 mg/m(2). This tendency was seen in patients with a low serum albumin level.

Analysis of hepatic disposition of native and galactosylated polyethylenimine complexed with plasmid DNA in perfused rat liver.

We studied the intrahepatic disposition characteristics of galactosylated polyethylenimine (Gal-PEI)/plasmid DNA (pDNA) complexes using rat liver perfusion experiment. After intraportal administration, transfection activity in liver of Gal-PEI complexes was approximately 26-fold higher than that of native PEI complexes. To evaluate the relationship between hepatic gene expression and disposition profiles, hepatic disposition of Gal-PEI complexes were pharmacokinetically analyzed by use of perfused rat liver, which enables uptake characteristics intrinsic to the liver to be elucidated. Moment analysis revealed that both complexes exhibited very high single-pass extraction. To characterize each kinetic process in hepatic uptake of Gal-PEI complexes, their outflow profiles were analyzed based on a two-compartment dispersion model. Consequently, the tissue binding affinity of Gal-PEI complexes was 3.0-fold larger than that of native PEI complexes, suggesting the increasing of hepatic binding affinity much enhanced the hepatic gene transfection efficiency. In contrast, galactosylation of PEI did not affected internalization (and/or sequestration) rate.