The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 microm. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. alpha-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10(-11)) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n = 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of alpha-fetoprotein levels.
DC Bead is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R (2) > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro-in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.
To assess the impact of the diagnosis and modern treatment of childhood cancer on achievement of adult goals, the authors evaluated employment, health and life insurance coverage, marriage, divorce, and reproduction in 227 former pediatric cancer patients. Each area was evaluated in relation to a common set of disease and demographic factors that included age at follow-up, age at diagnosis, gender, marital status, history of disease recurrence, and diagnosis. Patients were younger than 20 years of age at diagnosis, and their diagnoses were made between January 1,1960, and December 31,1984. The median age at diagnosis was 11.4 years, and the median age at follow-up was 26.6 years. The percentage of unemployed male respondents did not differ from population norms. The percentage of unemployed female respondents, however, was slightly higher than that of the United States population. Approximately 11% of the survivors reported some form of employment-related discrimination, a level significantly lower than that of prior reports. Company-offered health insurance was provided to 92.4% of full-time and 90.0°/o of part-time employed respondents. Life insurance was purchased by 60% of full-time employed men and 55% of women. These percentages were lower than those reported for the United States population. Twenty-four percent of those with life insurance had difficulty obtaining it. Fifty-eight percent of the subjects were married or lived as married. The percentages of married men and women were significantly lower than United States norms. Twenty percent of those who were married or lived as married have divorced or separated or no longer live as married. Women aged 20 to 24 years were less likely to marry, and women aged 35 to 44 years had a significantly higher frequency of divorce than similarly aged United States women. In general, the history of childhood cancer did not influence the decision to marry or live as married but was occasionally (20°/0] important in the decision to dissolve a marital relationship. Many former patients indicated that their diagnosis and treatment for childhood cancer influenced their decision to have children. The current study suggests that most former pediatric cancer patients achieve adult life goals. Additional research is necessary to define those populations at greatest risk of failure to achieve these goals.
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