A potential side effect of ABT-199 is the induction of tumor lysis syndrome [239], which can be controled by step-wise dose escalation.
Step-wise dose escalation should ameliorate this problem and initial clinical trials of ABT-199 use in the treatment of CLL look promising with many patients displaying responses.
The design was a single blind, across subjects, placebo controlled, group wise dose escalation using doses of 20, 35, 50 and 100 mg β-methyl-6-chloromelatonin.
IκBα increased alveolar IL-10 and KGF concentrations, with a step-wise dose effect seen.
The initial starting dose of docetaxel was 50 mg m−2 (dose level 1), and step-wise dose increases to 60 and 70 mg m−2 were planned for successive patient cohorts (dose levels 2 and 3, respectively).
The 12 PMs and 12 IMs included in the pharmacokinetics study participated in a temporary one-step tamoxifen dose escalation during 2 months.
Since the dose-limiting toxicity in the initial part of the study was febrile neutropenia, this second-step dose escalation was undertaken (Chollet et al, 1998).
The traditional single-step dose escalation with three patients per dose level was then initiated with patient #3 receiving PEG-LD 20 mg m−2, the previous dose level for which patient #2 had no significant toxicities.
It has become the present author's experience that a step-wise escalation of the estrogen dose over 1 2 weeks, and in some cases longer, will ameliorate the toxicity and make the treatment tolerable.
This improvement is a necessary first step in the move towards dose escalation, with the potential for improved cure rates.
We performed the step-wise PEEP escalation process in pigs with healthy lungs, pigs with diseased lung and reduced compliance may affect results.
