Purpose: Cetuximab in combination with chemotherapy is a standard-of-care first-line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX) has never before been proven in a controlled and randomized phase III trial. To our knowledge, the TAILOR trial ( ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter, phase III study of the addition of cetuximab to first-line FOLFOX prospectively choosing a RAS wt population and thus providing confirmative data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone. Patients and Methods: TAILOR is an open-label, randomized (1:1), multicenter, phase III trial in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt ( KRAS/ NRAS, exons 2 to 4) mCRC. The primary end point of TAILOR was progression-free survival time; secondary end points included overall survival time, overall response rate, and safety and tolerability. Results: In the modified intent-to-treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4 significantly improved the primary end point of progression-free survival time compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004; median, 9.2 v 7.4 months, respectively), as well as the secondary end points of overall survival time (current assessment after 300 events: hazard ratio, 0.76; 95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v 39.5%, respectively). Treatment was well tolerated, and there were no new or unexpected safety findings. Conclusion: The TAILOR study met all of its objectives and relevant clinical end points, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS wt mCRC.

Pancreatic cancer is characterized by aggressive and highly metastatic phenotypes. This disease exhibits a poor patient prognosis and is considered a challenge due to the limited treatment options encountered in clinical practice. Previous studies have shown that ruscogenin, a saponin found in the root of Ophiopogon japonicus, exerts a wide range of biological functions including anticancer activity. In the present study, the effects of ruscogenin were investigated on pancreatic cancer cells and the potential molecular mechanism of this compound was explored. Cell viability was assessed using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Cell death was measured by trypan blue staining and by flow cytometry. The number of iron oxide nanoparticles was measured using Prussian blue staining. Reactive oxygen species (ROS) production was assessed using flow cytometry with dihydroethidium staining. Protein expression of the associated genes was assayed by western blotting. Furthermore, in vivo experiments were conducted to confirm the antitumor effects and assay the potential toxicity of ruscogenin in a nude mouse xenograft model. The results indicated that ruscogenin significantly repressed cell viability and induced cell death of pancreatic cancer cells in vitro in a dose‑ and time‑dependent manner. Furthermore, ruscogenin increased the concentration of intracellular ferrous irons and the production of ROS. This effect was inhibited by deferoxamine (DFO). Ruscogenin induced ferroptosis by regulating the levels of transferrin and ferroportin. These two proteins were involved in ruscogenin‑induced pancreatic cancer cell death. Finally, in vivo experiments demonstrated the antitumor effect of ruscogenin on pancreatic cancer xenografts in the absence of apparent toxicity. Taken collectively, the data demonstrated that ruscogenin exhibited anticancer effects in pancreatic cancer cells by inducing ferroptosis. The findings suggested that this compound may be further developed as a promising anticancer candidate for the treatment of pancreatic cancer.