Three different treatment schedules have been explored in phase-I trials (Table 1).
In fact, such approaches are being explored in phase III trials.
In addition there is a dramatic lack of new antimicrobial agents being explored in phase 2 or 3 clinical trials, especially for Gram-negative organisms, and development of an antimicrobial with a genuinely novel mechanism of action is estimated to take years [2].
Based on preclinical models, dual inhibition of both IGF1R - with either monoclonal antibodies or tyrosine kinase inhibitors - and mTOR results in a superior antiproliferative effect over each single strategy [ 5], and this combination is now being explored in phase I/II trials in patients with breast cancer.
In addition there is a dramatic lack of new antimicrobial agents being explored in phase 2 or 3 clinical trials, especially for Gram-negative organisms, and development of an antimicrobial with a genuinely novel mechanism of action is estimated to take years [ 2].
This group of patients could possibly benefit of more individualised treatments, such as selective COX-2 inhibitors, which are already approved for treatment of familial colorectal adenomatous polyposis, and started to be explored in Phase I II studies (Snyderman, 2001).
Given the schedule dependency observed preclinically, three regimens were explored in phase I studies: (1) 0.2–5.2 mg m−2 daily for 5 days every 3 weeks (McDonald et al, 1998); (2) 10 40 mg m−2 weekly for 4 weeks repeated every 6 weeks (Rinaldi et al, 1995); and (3) 50–700 mg m−2 every 3 weeks (Rinaldi et al, 1999).
Table 1 Model parameters and their range of values that were explored in Phase-I of simulation experiments Parameter Values explored Description num-agents 1000, 2500, 5000, 7500, 10,000 The number of agents in the model love-radar 1, 2, 3 The diameter of an agent's ego network through which potential partners are sought.
This has extensively been explored in several phase I and II studies.
The combination of erlotinib and bevacizumab has already been explored in a phase II study (Friberg et al, 2006), with two responses seen in 13 patients.
