Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary end-points, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Involvement of nitric oxide system on anxiolytic-like behaviors induced by cholestasiss

The mechanisms of hepatic encephalopathy are not fully understood. Moreover, there is no comprehensive data concerning the effects of nitric oxide [NO] system on anxiolytic-like behaviors induced by bile duct ligation [BDL]. Male mice weighing 25-30 g were used and anxiety-like behaviors were tested using hole-board task. The data indicated that cholestasis increased the number of head-dipping but did not alter other aspects of behavior, 7 days after BDL, suggesting an anxiolytic-like response. Furthermore, the results showed that intraperitoneal [i.p.] injection of L-arginine [200 and 250 mg/kg] 15 min before testing induced anxiolytic-like behaviors in the normal animals, 4 and 7 days after BDL [considering that the dose of 200 mg in the normal mice is ineffective but is effective in the BDL mice]. On the other hand, injection of L-NAME [35 and 45 mg/kg, i.p.] 15 min before testing induced anxiogenic-like behaviors in the normal animals, 4 and 7 days after BDL [the dose of 35 mg/kg in the normal mice is ineffective but is effective in the BDL mice]. Moreover, injection of ineffective doses of L-NAME [25 and 35 mg/kg, i.p.] 15 min before administration of L-arginine [250 mg/kg, i.p.] and 7 days after BDL, decreased anxiolytic-like behaviors, significantly. Cholestatic mice show anxiolytic-like behaviors suggesting the involvement of the nitric oxide system