Tumour response sellckchem Objective tumour response data for all 63 patients are summarised in Table 2. Reductions in AFP were accompanied by imaging evidence of partial response in one patient (2%, 95% CI 0�C9%), stable disease in one patient, and progressive disease in two patients. Table 2 Tumour responses Survival Survival status is shown in Table 3 and Figure 1. After a median follow-up of 12 months, the median survival was 8 months (range 1�C25 months), and five patients remain on treatment 21�C25 months after starting. There was no statistically significant relationship between receptor expression by octreotide scintigraphy and survival duration (P=0.33) (Figure 2). Figure 1 Overall survival. Figure 2 Survival, by baseline octreotide scintigraphy status.

The small graph shows the hazard ratio of the negative group (?) compared with the positive group (+). Table 3 Survival status at March 2003 Treatment was well tolerated. Table 4 shows the main toxicities, including diarrhoea, abdominal cramping, and alterations in blood sugar (chiefly hyperglycaemia). Most toxicities were grade 1 or 2; the only grade 3 or 4 toxicities were diarrhoea, alterations in blood sugar, and anorexia. Diarrhoea is a common symptom in patients with advanced HCC even in the absence of any treatment. Table 4 Toxicity: numbers of patients with each grade as their most severe during their course of treatment Adverse events Most of the adverse events were attributable to chronic liver disease and its complications (Table 5). All deaths were attributable to progressive HCC.

Two adverse events had unrelated causes (incarcerated inguinal hernia and an abscess). Table 5 Serious adverse events Gastrointestinal bleeding With a total follow-up approaching 4000 patient-months, gastrointestinal bleeding occurred in four of 63 patients. In one patient, this was from peptic ulcer disease and in the others was from varices. Pharmacokinetics, receptors, and markers Pharmacokinetic evaluation was performed on 62, 41, 25, and 7 patients at baseline and after 3, 6, and 9 months of treatment, respectively. The mean trough plasma concentration at 3 months was 2205pgml?1 (range 678�C6166pgml?1). After 6 months, the mean concentration of plasma octreotide was 3377pgml?1 (range 956�C14290pgml?1), and after 9 months, 3238pgml?1 (1307�C9926pgml?1).

Evaluation of those patients who remained on the study for 6 months or more showed no evidence GSK-3 of accumulation of octreotide in plasma. Although plasma concentrations fluctuated, they were generally within the range 1000�C3000pgml?1. Serum AFP was elevated in 50 patients (79%). In four of these it fell, individually, from 578 to 2, from 1600 to 2, from 48 to 23, and from 1368 to 56IUml?1. Serum for chromogranin A estimation and pharmacokinetics was available from 59 patients (94%), and tissue was available for IHC analysis of somatostatin receptors from 20 samples from 19 patients (44%); one patient had two tumours.