With roles of blocking cell proliferation, cyclin-dependent protein kinase (CDK) 4/6 inhi-bitors are effective and safe complementary therapies for hormone receptor-positive breast cancer. CDK4/6 inhibitors combined with endocrine therapy significantly improve the prognosis of patients with advanced or metastatic breast cancer, especially those with endocrine resistance. Indications for CDK4/6 inhibitors are also expected to broaden into early-stage breast cancer. However, mechanisms of resistance of CDK4/6 inhibitors remain elusive.

Background and purpose:Rectal cancer is one of the malignant tumors that seriously harm human health in the world,ranking third in incidence and second in mortality.With the development of social and economic level,the incidence and mortality of colorectal cancer in China are increasing,and China becomes one of the countries with high incidence of colorectal cancer disease in the world.The recommended treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery,which greatly improves the prognosis of patients.However,intestinal adverse reactions such as diarrhea caused by neoadjuvant chemoradiotherapy are increased,and some patients are forced to delay or interrupt treatment due to serious side effects.Amifostine is a broad-spectrum normal cell protective agent,which has good protective effect against various radiochemotherapy toxicity.We conducted a retrospective analysis of patients with locally advanced rectal cancer who received neoadjuvant radiotherapy combined with irinotecan concurrent chemotherapy to investigate whether concurrent use of amifostine alleviated gastrointestinal and hematological toxicities.Methods:A retrospective cohort analysis was used in this study.Clinical data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy at the Affiliated Cancer Hospital of Fudan University during the period of discharge from January 1,2018 to December 31,2019 were retrospectively collected.The patients were divided into 2 groups by whether amifostine was used during the same period.The main purpose of the study was to analyze whether amifostine can reduce gastrointestinal and hematological toxicities,and secondary objectives included whether amifostine could alter tumor marker levels,mesorectal fascia invasion(MRF)positive rate,extramural vascular invasion,positive rate of EMVI and pathological complete response(pCR).Using SAS9.4 statistical software,the normality test was carried out for continuous variables.The rank sum test of Wilcoxon was performed when the diarrhea grade did not conform to normal distribution.Analysis of variance was performed for intra-group comparison,and Wilcoxon rank sum test was performed for inter-group comparison.Because of the imbalance between groups,the difference between the two groups was compared using a generalized linear model.This study strictly followed the STrengthening the Reporting of OBservational studies in Epidemiology(STROBE)guidelines to ensure the transparency of the research methodology and the reliability of the results.Results:Finally,154 eligible patients were included,of whom 78 were in the amifostine group and 76 were in the control group.The highest grade of diarrhea in amifostine group was 1.00(1.00,1.00),lower than that in control group(2.00,3.00),and the difference between groups was statistically significant(P＜0.01).After radiotherapy,white blood cell count(WBC),hemoglobin(HB)and absolute neutrophil count(ANC)from the two groups were obtained.ANC and platelet count(PLT)showed no statistically significant difference(P＞0.05),and the lowest values of WBC,RBC and PLT did not have statistically significant difference between the two groups during neoadjuvant period(P＞0.05).Amifostine may not alleviate hematological toxicity.Carbohydrate antigen 72-4(CA72-4)(Z=2.22,P=0.03),carbohydrate antigen 50(CA50)(Z=-2.49,P=0.01)and carbohydrate antigen 24-2(CA24-2)had statistically significant difference(Z=-2.29,P=0.02).There were no significant differences in MRF positive rate(P=0.11),EMVI positive rate(P=0.61)and pCR rate(P=0.94)between the two groups.Conclusion:Concurrent administration of amifostine in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy can reduce gastrointestinal toxicity and reduce the levels of tumor markers CA72-4,CA50 and CA24-2.However,it may have no significant effect on improving hematological toxicity,MRF and EMVI positive rate and pCR rate.