Unresolved diarrhoea was further treated with opiates and infusion therapy during hospitalisation, as needed. On the basis of clinical selleck inhibitor and preclinical data, a nutritional supplement was used that demonstrated a potential beneficial effect on the gut mucosa and bowel function; use of the supplement showed promising results in patients with CID (Gibson, 1998; Belluzzi et al, 2000; Bjorck et al, 2000; Daniele et al, 2001; Juntunen et al, 2001). The nutritional supplement was administered once daily in a 250-ml serving that contained omega-3 fatty acids (0.5g docosahexaenoic acid and 1g eicosapentaenoic acid), short-chain fructo- (5g) and galactooligosaccharides (5g), high-quality egg protein with anti-secretory factor (3g) and probiotic Bifidobacterium lactis (2g) and glutamine (5�C10g).

The administration of nutritional supplement was started 7 days before and continued daily upon initiation of patupilone treatment during the entire course of therapy. Safety and response assessments Routine clinical and laboratory assessments were conducted at baseline, before each treatment and at the end of study visit. Electrocardiograms were performed at baseline and at the end of treatment. AEs were recorded and graded using the NCI-CTC v2.0, and they were assessed by the investigator for any relationship with patupilone treatment. Objective measurement of tumour mass was assessed in accordance with Response Evaluation Criteria in Solid Tumours v1.0 at baseline and thereafter every 8 weeks. Complete (CR) and partial responses (PR) were to be confirmed at least 4 weeks after the initial declaration of response.

Efficacy variables included best overall response and time to progression (TTP). Pharmacokinetic assessments In the 20MI arm, blood samples were collected during cycles 1 and 4 before drug administration, at the end of infusion and 0.5, 1, 2, 4, 8, 24, 168, 336 and 504h post-infusion start. For the CI-1D arm, samples were collected during cycle 1 before drug administration, at 4, 8 and 24h (during infusion) and 24.17, 24.33, 24.67, 25, 26, 28, 32, 48, 72, 168, 336 and 504h post-infusion start. For the 16HI-5D arm, blood samples were collected during cycle 1 before drug administration, at 16, 24, 40, 48, 64, 72, 88, 96 and 112h (during infusion) and 112.17, 112.33, 112.67, 113, 114, 116, 120, 144, 168, 336 and 504h post-infusion start. Patupilone concentrations in blood were analysed by liquid chromatography-tandem Dacomitinib mass spectrometry with a detection limit of 0.1ngml�C1 (Forster et al, 2007). Pharmacokinetics (PK) of patupilone was determined using a non-compartmental analysis method (Win-Nonlin; Pharsight, Mountain View, CA, USA), and the area under the concentration�Ctime curve (AUC) was calculated by linear trapezoidal method.