 The pharmacokinetic profile for decitabine has been well described and offers several possible dosing schedules feasible for clinical practice and combination with other agents. Decitabine is currently being tested in combination with standard cytotoxic agents. It has shown some activity in solid tumors, however, myelosuppression is a common side effect, especially when given concurrently with other myelosuppressive therapy carboplatin Appleton et al., 2007; Plimack et al., 2007. We propose a novel study using decitabine in combination with a non-myelosuppressive targeted biological agent as well as giving it sequentially rather than concurrently to try to maximize the effect of the second drug by dosing it during the demethylation window. In the dose-finding study reported by Appleton et al., they recommended a dose of 90 mgm2 over 6 hours every 28 days, but went up as high as 135 mgm2 and combined this with carboplatin Appleton et al., 2007. We have chosen a dose of 45 mgm2 decitabine every 14 days based on its reported safety and biological equivalence from this study. There was no grade 3 or 4 hematological toxicities observed with 3 patients infused with 45 mgm2 of decitabine followed by 5 AUC carboplatin; there was 1 episode of grade 3 leukopenia and 1 of grade 3 neutropenia in 4 patients infused with 45 mgm2 of decitabine followed by 6 AUC carboplatin Appleton et al., 2007. At the higher dose of 90 mgm2 with 5 AUC carboplatin in 13 patients, 5 episodes of grade 4 leukopenia or neutropenia were observed; in 10 patients with 90 mgm2 and 6 AUC carboplatin, there were 4 episodes of grade 4 leukopenia or neutropenia. The proposed infusion over 2 hours should not create any infusion rate toxicities and will be a schedule patients will tolerate. Daily lower dose infusions used in hematological disorders maybe be efficacious but daily intravenous chemotherapy impacts patients quality of life significantly. Decitabine also has an elimination half-life of 30 minutes, so will clear the body rapidly. The proposed administration of the decitabine twice, at half the dose, in a 28-day period should be better tolerated than the 90 mgm2 combined with carboplatin. The myelosuppressive toxicity which is the main toxicity of decitabine should be less significant as it is not being combined with a second myelosuppressive agent as it was with carboplatin. Low dose decitabine 45 mgm2 has nearly equivalent hypomethylating effects to 90 mgm2 in both blood and buccal cells. The more frequent dosing every 2 weeks versus every 4 weeks should maintain the hypomethylating effect at a lower dose. Additionally, we propose a novel dosing schedule where our second agent, panitumumab, will be given on alternating weeks and targeting the EGFR pathway when it is hypomethylated from the prior decitabine treatment. Our work as well as others, has demonstrated that specific promoter hypomethylation is observed by 8-14 days after the start of treatment and genomic DNA reverts to baseline levels by 28 to 35 days after the start of treatment Appleton et al., 2007; Samlowski et al., 2005, Kantarjian, 2007 23. 