Serum basic fibroblast growth factor and interleukin-1βpredict the effect of first-line chemotherapy in patients with advanced gastric cancer

BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St.Mary’s Hospital.Patients were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR levels.To determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was applied.We evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire cohort.RESULTS We included 271 patients in this study.Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and PFS.Post-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for OS.When CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group.Within the CA19-9-negative group,the posttreatment NLR<2.62 group showed better survival than the post-treatment NLR≥2.62 group(OS 12.7 mo vs 7.7 mo,P<0.001;PFS 6.7 mo vs 2.1 mo,P<0.001),and post-treatment NLR showed correlation with clinical response.CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy,the combination of post-treatment NLR<2.62 and 18%decline of CA19-9 at the first response evaluation is a good prognostic marker.Post-treatment NLR<2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.

Beyond first-line chemotherapy for advanced pancreatic cancer:An expanding array of therapeutic options?

While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyond is less well defined.A variety of cytotoxic agents,either alone or in combination,have been evaluated,although primarily in the context of small single-arm or retrospective studies.Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8mo,highlighting the very poor prognosis of patients who are candidates for such treatment.Targeted therapies studied in this chemotherapy-refractory setting,meanwhile,have produced even worse efficacy results.In the current article,we review the clinical evidence for treatment of refractory disease,primarily in patients who have progressed on front-line gemcitabine-based chemotherapy.In the process,we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting,including how to select an appropriate control arm given the absence of a wellestablished reference standard,and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

Oxaliplatin,Fluorouracil and Leucovorin (FOLFOX) as First-line Chemotherapy for Metastatic or Recurrent Colorectal Cancer Patients

OBJECTIVE To investigate the efficiency and safety of the oxaliplatin, fluorouracil(5-FU)and leucovorin regimen(FOLFOX)in previously untreated patients with metastatic or recurrent colorectal cancer. METHODS Previously untreated patients with metastatic or recurrent colorectal cancer received 100 mg/m2 of oxaliplatin intravenously(IV)over 2 h on day 1,and IV 400 mg/m2 of leucovorin over 2 h followed by a bolus of 400 mg/m2 of 5-FU.Then 2,600~3,000 mg/m2 of 5-FU was administered by continuous infusion over 46 h. RESULTS An evaluated response rate was determined for 97 of 105 treated patients.The overal response rate was 35.1%,9 patients(9.3%) had a complete response and 25 patients(25.8%)a partial response.Thirty-two patients(33.0%)developed stable disease and 32.0%of the patients progressed.The median time to progression(TTP)was 7.7 months and the median overal survival 20.5 months.One and 2-year survival rates were 68%and 32%.Toxic effects based on the National Cancer Institute-Common Toxicity Criteria(NCI-CTC),reaching grade 3/4 were:neutropenia 12.3%, anemia 11.3%,vomiting 4.1%and diarrhea 7.2%.Grade 3 neuropathy was 5.1%.The overall survival rate of patients who had received a radical resection was superior to the patients who had not received a operation,or had received a pal iative resection(P=0.0658).The serum levels of CEA,ALP and LDH had no relationship with survival(P>0.05). CONCLUSION The FOLFOX regimen containing oxaliplatin,5-FU plus leucovorin was an efficacious regimen with good tolerability in previously untreated metastatic or recurrent colorectal cancer patients.

New prognostic model for patients with advanced gastric cancer:Fluoropyrimidine/platinum doublet for first-line chemotherapy

BACKGROUND New prognostic factors have been reported in patients with metastatic or recurrent gastric cancer(MRGC),necessitating modifications to the previous prognostic model.AIM To develop a new model,MRGC patients who received fluoropyrimidines/platinum doublet chemotherapy between 2008 and 2015 were analyzed.METHODS A total of 1883 patients was divided into a training set(n=937)and an independent validation set(n=946).RESULTS Multivariate analysis showed that the following six factors were associated with poor overall survival(OS)in the training set:Eastern Cooperative Oncology Group performance score≥2 and bone metastasis(2 points each),peritoneal metastasis,high alkaline phosphatase level,low albumin level,and high neutrophil-lymphocyte ratio(1 point each).A prognostic model was developed by stratifying patients into good(0-1 point),moderate(2-3 points),and poor(≥4 points)risk groups.In the validation set,the median OS of the three risk groups was 15.8,10.1,and 5.7 mo,respectively,and those differences were significant(P<0.001).CONCLUSION We identified six factors readily measured in clinical practice that are predictive of poor prognosis in patients with MRGC.The new model is simpler than the old and more easily predicts OS.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer:Gemcitabine monotherapy vs combination chemotherapy

BACKGROUND Combination chemotherapy(gemcitabine plus nab-paclitaxel and FOLFIRINOX)is widely used as the standard first-line treatment for pancreatic cancer.Considering the severe toxicities of combination chemotherapy,gemcitabine monotherapy(G mono)could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status.However,reports on the efficacy of G mono in patients older than 75 years are limited.AIM To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.METHODS We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono(n=45)or combination therapy(n=59)as a first-line treatment between 2011 and 2019.All patients were histologically diagnosed with ductal adenocarcinoma.Primary outcomes were progression-free survival and overall survival.We also analyzed subgroups according to age[65-74 years(elderly)and≥75 years(very elderly)].Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.RESULTS The baseline characteristics were significantly different between the two chemotherapy groups,especially regarding age,ratio of multiple metastases,tumor burden,and Eastern Cooperative Oncology Group performance status.After propensity score matching,the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients.In the elderly patients,the median progression-free survival(62 d vs 206 d,P=0.000)and overall survival(102 d vs 302 d,P=0.000)were longer in the combination chemotherapy group.However,in the very elderly patients,the median progression-free survival(147 d and 174 d,respectively,P=0.796)and overall survival(227 d and 211 d,respectively,P=0.739)were comparable between the G mono and combination chemotherapy groups.Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group,especially thromboembolism(G mono vs nab-paclitaxel vs FOLFIRINOX;8.9%vs 5.9%vs 28%,P=0.041),neutropenia(40.0%vs 76.5%vs 84.0%,P=0.000),and neuropathy(0%vs 61.8%vs 28.0%,P=0.006).CONCLUSION In elderly patients,combination therapy is more effective than G mono.However,G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

Nutritional status changes in patients with advanced non-small cell lung cancer receiving first-line chemotherapy

Objective This study aimed to assess the real-life nutritional status changes and gastrointestinal symptoms in patients with advanced non-small cell lung cancer(NSCLC) receiving chemotherapy.Methods A total of 104 patients with metastatic NSCLC receiving first-line chemotherapy were included in this study. Unintentional weight loss, body mass index(BMI) changes, and gastrointestinal symptoms were recorded and evaluated. Biochemical parameters [hemoglobin(Hb) and albumin levels] were compared before and after two chemotherapy cycles using SPSS software.Results Of these patients, 65.38%(68/104) experienced unintentional weight loss, whereas 30.77% and 12.5% presented with ≥ 5% and ≥ 10% degrees of weight loss, respectively, within 6 months before first-line chemotherapy was administered. Then, 48.08%(50/104) of the patients experienced unintentional weight loss after two chemotherapy cycles. The mean body weight after chemotherapy was 61.47 ± 10.37 kg, which was significantly decreased relative to that before chemotherapy(P < 0.05). The mean BMI after chemotherapy was 22.66 ± 3.34 kg/m^2, which was also significantly diminished with respect to that during the previous chemotherapy cycle(P < 0.05). The most common gastrointestinal symptoms reported among all the study patients were anorexia(80/104, 76.92%), nausea(53/104, 50.96%), constipation(49/104, 47.12%), vomiting(48/104, 46.15%), taste disorders(40/104, 38.46%), and early satiety(32/104, 30.77%). The mean Hb levels after chemotherapy were 117.06 ± 16.67 g/L, which were significantly lower than those before chemotherapy(132.73 ± 16.42 g/L)(P < 0.05). No significant difference was noted between the mean albumin levels before and after chemotherapy(38.29 ± 4.22 g/L vs 38.17 ± 4.54 g/L; P = 0.798). Conclusion Weight loss history, gastrointestinal symptoms, and Hb level decreases are determinant factors of nutritional status in patients with advanced NSCLC and must be included in the screening, evaluation, and treatment of lung carcinoma.

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L150%or more(EMPOWER-Lung 1):35-month follow-up from a multicentre,open-label,randomised,phase 3 trial

肺癌是全球癌症相关死亡的主要原因,非小组胞肺癌(NSCLC)占所有肺癌病例的80%-85%。随着分子生物学的发展,针对驱动基因突变(如EGFR、ALK等)的靶向药物治疗已成为晚期NSCLC的标准一线治疗。但大多数NSCLC并没有可检测到的驱动基因突变,传统的铂类化疗效果不佳。免疫检查点抑制剂的出现极大地改变了这一领域的治疗格局。PD-1/PD-L1抑制剂已被证实可以显著提高NSCLC患者的疗效和生存期,特别是PD-L1表达阳性率≥50%的人群。

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma:A case report and review of literature

BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed cell death 1(PD-1)inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors,there are few reports regarding initial immunochemotherapy in advanced MPeM.CASE SUMMARY Here,to our knowledge,we present the first case of a patient with epithelioid subtype MPeM,who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival(PFS)and good tolerance.A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen.Computed tomography revealed a solid mass in the lower abdomen,which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy.The patient received eight cycles of pemetrexed 800 mg(day 1),cisplatin 60/50 mg(day 1–2),and zimberelimab(PD-1 inhibitor)240 mg(day 1)every 3 wk.He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms.The best tumor response was partial remission with a final PFS of 7 mo.No immunerelated adverse event occurred during the combination treatment.CONCLUSION The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer： a meta-analysis

Background What benefits and toxicities patients acquire from the use of bevacizumab combined with first-line chemotherapy remains controversial.This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer （mCRC）.Methods Several databases,including PubMed,Embase,and Cochrane Library,were searched up to April 30,2013.Eligible studies were only randomized,controlled trials （RCTs） with a direct comparison between mCRC patients treated with and without bevacizumab.Overall risk ratio （RR）,hazard ratio （HR）,odds ratio （OR）,and 95％ confidence intervals （CO were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.Results Six RCTs,including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group,were included.Overall,the addition of bevacizumab to first-line chemotherapy increased overall response rate （ORR） by 4.5％,prolonged both progression-free survival （PFS） and overall survival （OS）,and increased the rate of total Grades 3 or 4 adverse events （G3/4AEs） by 6.9％.Significant differences were found in ORR （RR=1.22 （95％ CI 1.01-1.46）,P=0.03）,PFS （HR=0.60 （95％ Cl 0.47-0.77）,P ＜0.0001）,OS （HR=0.83 （95％ Cl 0.70-0.97）,P=0.02）,and any G3/4AEs （OR=1.56 （95％ Cl 1.29-1.89）,P ＜0.00001）.Conclusion Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC,because of conferring a significant improvement in ORR,PFS,and OS,even though it increased adverse events.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

Objective： To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 （HER2）-overexpressing advanced breast cancer. Methods： A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3（＋） staining in immunochemistry or amplification of fluorescence in situ hybridization （FISH, ratio ≥2.0）. Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival （PFS） and overall survival （OS）. Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox＇s proportional hazards regression model, and the level of significance was P〈0.05. Results： All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 （80.00%） patients had visceral metastasis, and 43 （47.78%） patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months （range, 2-59 months）, and the median OS after metastasis or initially local advanced disease was 22 months （range, 2-1 16 months）. Conclusions： Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

Objective： Data on the clinical activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in patients with non-small-cell lung cancer （NSCLC） and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods： We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results： Seventy patients （13.9%） harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate （ORR） and median progression-free survival （mPFS） of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group （ORR： 23.3% vs. 51.8%, P=0.003; mPFS： 7.1 vs. 10.9 months, P〈0.001）. In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy （7.1 vs. 6.1 months, P=0.893）. In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant （G719X： 8.2 vs. 5.8 months, P=0.061; L861Q： 7.6 vs. 4.1 months, P=0.872）. Multivariate analyses identified adenocarcinoma （P=0.003） as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions： The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR- TKIs.

The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer

Background: Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods: Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2;irinotecan, 150 mg/m2;l-leucovorin, 200 mg/ m2;and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results: Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1-12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76-14.44) and 5.77 (95% CI 5.00-6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions: Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Cyclophosphamide, Thalidomide and Dexamethasone (CTD) as First-Line Therapy in Multiple Myeloma Patients: An Experience in a Clinical Haematology Centre in Dakar, Senegal

Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.

Patient-derived orthotopic xenograft models for cancer of unknown primary precisely distinguish chemotherapy,and tumor-targeting S.typhimurium A1-R is superior to first-line chemotherapy

Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.

Prognostic significance of peritoneal metastasis from colorectal cancer treated with first-line triplet chemotherapy

BACKGROUND Peritoneal metastasis from colorectal cancer(CRC)carries a poor prognosis in most studies.The majority of those studies used either a single-agent or doublet chemotherapy regimen in the first-line setting.AIM To investigate the prognostic significance of peritoneal metastasis in a cohort of patients treated with triplet chemotherapy in the first-line setting.METHODS We retrospectively evaluated progression-free survival(PFS)and overall survival(OS)in 51 patients with metastatic CRC treated in a prospective clinical trial with capecitabine,oxaliplatin,irinotecan,and bevacizumab in the first-line setting according to the presence and absence of peritoneal metastasis.Furthermore,univariate and multivariate analyses for PFS and OS were performed to assess the prognostic significance of peritoneal metastasis at the multivariate level.RESULTS Fifty-one patients were treated with the above triplet therapy.Fifteen had peritoneal metastasis.The patient characteristics of both groups showed a significant difference in the sidedness of the primary tumor(left-sided primary tumor in 60%of the peritoneal group vs 86%in the nonperitoneal group,P=0.03)and the presence of liver metastasis(40%for the peritoneal group vs 75%for the nonperitoneal group,P=0.01).Univariate analysis for PFS showed a statistically significant difference for age less than 65 years(P=0.034),presence of liver metastasis(P=0.046),lung metastasis(P=0.011),and those who underwent metastasectomy(P=0.001).Only liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.001 and 0.002,respectively.Multivariate analysis showed that age(less than 65 years)and metastasectomy were statistically significant for PFS,with P values of 0.002 and 0.001,respectively.On the other hand,the absence of liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.003 and 0.005,respectively.CONCLUSION Peritoneal metastasis in patients with metastatic CRC treated with first-line triple chemotherapy does not carry prognostic significance at univariate and multivariate levels.Confirmatory larger studies are warranted.

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.