Adjuvant chemotherapy in the absence of radiation has not, however, been shown to improve local control. Trials addressing this issue accrued patients during the pre-TME era. The NSABP R-01 trial

compared observation vs. adjuvant radiotherapy vs. adjuvant chemotherapy (fluorouracil, semustine, and vincristine) (2). The authors described an improvement in the 5-year disease-free survival and {TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor|TNF alpha inhibitor|TNF-alpha inhibitor| buy TNF-alpha inhibitor|TNF-alpha inhibitor ic50|TNF-alpha inhibitor price|TNF-alpha inhibitor cost|TNF-alpha inhibitor solubility dmso|TNF-alpha inhibitor purchase|TNF-alpha inhibitor manufacturer|TNF-alpha inhibitor research buy|TNF-alpha inhibitor order|TNF-alpha inhibitor mouse|TNF-alpha inhibitor chemical structure|TNF-alpha inhibitor mw|TNF-alpha inhibitor molecular weight|TNF-alpha inhibitor datasheet|TNF-alpha inhibitor supplier|TNF-alpha inhibitor in vitro|TNF-alpha inhibitor cell line|TNF-alpha inhibitor concentration|TNF-alpha inhibitor nmr|TNF-alpha inhibitor in vivo|TNF-alpha inhibitor clinical trial|TNF-alpha inhibitors|TNF-alpha signaling inhibitor|TNF-alpha pathway inhibitor|TNF-alpha signaling pathway inhibitor|TNF-alpha signaling inhibitors|TNF alpha pathway inhibitors|TNF-alpha signaling pathway inhibitors|TNF-alpha inhibitor library|TNF-alpha activity inhibition|TNF-alpha activity|TNF-alpha inhibition|TNF-alpha inhibitors library|TNF alpha inhibitor libraries|TNF-alpha inhibitor screening library|TNF-alpha high throughput screening|TNF-alpha inhibitors high throughput screening|TNF-alpha phosphorylation|TNF-alpha screening|TNF-alpha assay|TNF-alpha animal study| overall survival Inhibitors,research,lifescience,medical in the chemotherapy arm vs. observation arm, but not local control (Table 6). Table 6 NSABP R-01(2) Similarly, a prospective trial by the Gastrointestinal Tumor Study Group did not show a decrease in local control with the addition of chemotherapy alone to surgery. This trial randomized patients to surgery followed by observation, chemotherapy, radiotherapy or chemoradiotherapy (1),(26),(27). The trial was closed early due Inhibitors,research,lifescience,medical to inferiority of the surgery alone arm and thus the data was not sufficiently powered to distinguish outcomes all four treatment arms. At a median of 80 Inhibitors,research,lifescience,medical months, the locoregional recurrence and overall survival were improved by adjuvant

chemoradiotherapy, but not by either therapy alone (Table 7). Table 7 GITSG 71-75(1),(26),(27) Randomized trials showed that the addition of radiation to chemotherapy improved local control in the pre-TME era, but the benefit of adding radiation to modern chemotherapy following TME is not known (1), (19), (26). The Dutch study of TME with or without short course preoperative radiation therapy proved that the addition Inhibitors,research,lifescience,medical of radiation to TME improves local control, but this trial did not use chemotherapy. It is possible, though not proven, that the lower disease burden afforded by modern surgical techniques may be amenable to local control with chemotherapy, particularly with the use of newer, more active chemotherapy regimens. These advances Inhibitors,research,lifescience,medical may obviate the benefit of adjuvant radiotherapy in some

patients. The most notable advances in chemotherapy for rectal cancer are oxaliplatin and irinotecan. Oxaliplatin is a platinum derivative that acts as an alkylating agent and impairs DNA replication and transcription. A randomized trial by de Gramont et al. showed improvement in response rate in advanced colorectal cancer from 22% with infusional isothipendyl 5FU plus leucovorin to 50.7% with infusional 5FU, leucovorin, and oxaliplatin (FOLFOX), P=0.0001 (28). Irinotecan is a topoisomerase I inhibitor. A randomized trial by Douillard et al. showed improvement in response rate in advanced colorectal cancer from 22% with infusional 5FU plus leucovorin to 35% with infusional 5FU, leucovorin, and irinotecan (FOLFIRI), P<0.005 (29). While response rates are higher with the addition of newer agents to 5FU, it is unknown of these agents can provide equivalent local control compared to radiation.