Simple Summary Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Either cisplatin or oxaliplatin could be part of the chemotherapy regimen,... Show moreSimple Summary Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Either cisplatin or oxaliplatin could be part of the chemotherapy regimen, of which oxaliplatin is currently most used in the standard treatment. Evidence to choose oxaliplatin over cisplatin in the curative setting is limited. In this study, we compared cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with pre- and postoperative chemotherapy. Adverse events were not different for patients who received cisplatin versus those who received oxaliplatin, nor was compliance with the treatment regimen. We could not detect survival differences between patients treated with cisplatin versus oxaliplatin. Diarrhea more frequently impacted patients treated with oxaliplatin than patients treated with cisplatin. As hydration is not needed for oxaliplatin, it is more practical to use in daily care. In conclusion, both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer. (1) Background: Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Based on studies in patients with metastatic gastric cancer, oxaliplatin has replaced cisplatin in the curative setting as well. However, evidence to prefer oxaliplatin over cisplatin in the curative setting is limited. (2) Methods: We compared patient-related and tumor-related outcomes for cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with perioperative chemotherapy in the CRITICS trial. (3) Results: Preoperatively, 632 patients received cisplatin and 149 patients received oxaliplatin. Preoperative severe toxicity was encountered in 422 (67%) patients who received cisplatin versus 89 (60%) patients who received oxaliplatin (p = 0.105). Severe neuropathy was observed in 5 (1%) versus 6 (4%; p = 0.009) patients, respectively. Postoperative severe toxicity occurred in 109 (60%) versus 26 (51%) (p = 0.266) patients; severe neuropathy in 2 (1%) versus 2 (4%; p = 0.209) for patients who received cisplatin or oxaliplatin, respectively. Diarrhea impacted the quality of life more frequently in patients who received oxaliplatin compared to cisplatin. Complete or near-complete pathological response was achieved in 94 (21%) versus 16 (15%; p = 0.126) patients who received cisplatin or oxaliplatin, respectively. Overall survival was not significantly different in both groups (p = 0.300). (4) Conclusions: Both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer. Show less
Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal... Show moreBackground The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C- and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C-based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were signi?cantly associated with treatment outcome. The most promising genetic biomarkers wereERCC1rs11615,XPCrs1043953,XPDrs13181,XPGrs17655,MNATrs3783819/rs973063/rs4151330, MMR status, ATM protein expression,HIC1tandem repeat D17S5, andPIN1rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation. Show less
Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA)... Show moreApoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy. Show less
