Conclusion

There is now a wealth of information on phase I trials of P-ODNs in the field of oncology. Using different schedules, safety and tolerability profiles have been demonstrated with MTDs defined. Pharmacokinetic and pharmacody-

namic profiles are encouraging, with plasma levels of intact P-ODNs reaching concentrations predicted to be of therapeutic benefit to patients. Second-generation chemistries are being developed, and GEMĀ®231 (Hybridon) has completed phase II combination studies in cancer. Isis has explored AS-ODNs with 2'-methoxyethyl-modified flanking regions, and ISIS 104838, targeting TNF-a, is currently in phase II studies for the treatment of rheumatoid arthritis and psoriasis, and OGX-1 is in phase I studies for the treatment of cancer. Fine-tuning of antisense chemistries and delivery systems may result in improved therapies for the future with inclusion of AS-ODNs into new and conventional anticancer drug regimens.

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