A mechanistic interpretation of the substantially lower toxicity of citicoline compared with that of choline is lacking to date.
Selective serotonin reuptake inhibitors (SSRIs) have provided an improved tolerability profile compared to the TCAs through lower rates of adverse events, and substantially lower toxicity in overdose [ 4].
It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity.
More recently, Feany and colleagues reported that although single- or double-phosphorylation mutants did not appreciably alter toxicity compared with wild-type tau, one mutant consisting of five altered residues [Ser202/Thr205 (AT212 T212 (part of AT100) and T231/S235] did not exhibit substantially lower toxicity compared with wild-type tau (26).
However, the photochemical enhancement of scFvMEL/rGel toxicity was substantially lower when the immunotoxin was delivered directly after the light exposure of the A-375 cells (Figure S4).
In this concept, toxicity is substantially lower than with postoperative radiochemotherapy, and significant downstaging can be achieved with radiochemotherapy prior to surgery.
However, its toxicity is substantially lower than that for drugs with proven benefit in colorectal cancer such as fluoropyrimidines and oxaliplatin, whose side effects include neutropenia, increased risk of infection, nausea and vomiting, fatigue, alopecia and potential fertility loss.
The incidence of neurological toxicity was substantially lower than that reported in a recent phase I trial (Schmid et al, 2010), perhaps because patients in the previous study were more heavily pretreated (median of previous regimens 3 vs 1) and more likely to have had received previous neurotoxic agents, including taxanes, vinca alkyloids, and platinum compounds.
In comparison with cisplatin, oxaliplatin exhibits a favourable toxicity profile with a substantially lower rate of nephrotoxicity, ototoxicity, and myelosuppression (Extra et al, 1990; Misset et al, 2001; Louvet et al, 2002; Al-Batran et al, 2004; Suh et al, 2005; Park et al, 2006).
Some clinicians equate this with impending toxicity despite information which demonstrates that serum levels where neurological depression is seen (4 – 7 mEq/L) are substantially lower than serum levels that are associated with the toxicity-related side effects of absent patellar reflexes (>10 mEq/L), respiratory depression (>13 mEq/L) or cardiac (25 mEq/L) dysfunction [ 46].
Therefore properties different from the affinity must account for the high efficiency of morpholino oligos, however, also the toxicity of these molecules peaks at substantially lower concentrations compared to the mixed PNAs (see Figure 4E).
