Twenty-four hour intra-arterial infusion of 5-fluorouracil,cisplatin,and leucovorin is more effective than 6-hour infusion for advanced hepatocellular carcinoma

AIM. To evaluate the time dependence of intra-arterial 5-fluorouracil （5-FU） therapy for advanced hepatocellular carcinoma （aHCC）. METHODS： Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis were treated with combined intra-arterial 5-FU, cisplatin （CDDP）, and leucovorin （LV）. The Japan Integrated Staging score （JIS score） of each patient was 3 or more. The patients were divided into two groups, alter which the 15 patients in group S were treated with 6-h infusion chemotherapy （LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 4 h） and the 22 patients in group L were treated with 24-h infusion chemotherapy （LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 22 h）. Continuous infusion chemotherapy was performed v/a the proper hepatic artery every 5 d for 4 wk using an implanted drug reservoir. RESULTS： The percentages of patients with a partial response after 4 wk of chemotherapy were 6.7% in group S and 31.8% in group L. The survival of group L was significantly better than that of group S, with the median survival time being 496 d in group L and 226 d in group S （P 〈 0.05）. CONCLUSION： Continuous 24-h intra-arterial infusion is more effective for aHCC and can markedly prolong survival time as compared to 6-h infusion.

Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin,cisplatin, and 5-fluorouracil regimen for advanced gastric cancer:A systematic review and meta-analysis

BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better.AIM To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis.METHODS Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for analysis.RESULTS Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile neutropenia.CONCLUSION With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.

Effects of Xiaocangping tablets combined with 5-fluorouracil and cisplatin on immunity, tumor markers, angiogenesis and related factors in patients with advanced esophageal cancer

Objective:To explore the effects of Xiaocangping tablets combined with 5-fluorouracil and cisplatin on immunity, tumor markers, angiogenesis and related factors in patients with advanced esophageal cancer.Methods:86 patients with advanced esophageal cancer admitted to our hospital from March 2014 to February 2017 were randomly divided into control group (43 cases) and observation group (43 cases). All the subjects were treated with 5-fluorouracil plus cisplatin, and the observation group was treated with Xiaocangping tablets on this basis. The changes of immune function, tumor markers, angiogenesis and related factors in the two groups were compared and analyzed.Results:After treatment, the levels of CD4+, CD4+/CD8 + in both groups were significantly higher than those before treatment (P<0.05), while the levels of CD8+ were significantly lower than those before treatment (P<0.05), the levels of CD4+ and CD4+/CD8+ in the observation group were significantly higher than those in the control group (P<0.05), while the levels of CD8+ in the observation group was significantly lower than that in the control group (P<0.05);the levels of CA125, CEA and CA19-9 in the two groups were significantly lower than those before treatment (P<0.05), and the levels of CA125, CEA and CA19-9 in the observation group were significantly lower than those in the control group (P<0.05);the levels of VEGF, TGF-β1, MMP-9, NGAL in the two groups were significantly lower than those before treatment (P<0.05), and the levels of VEGF, TGF-β1, MMP-9, NGAL in the observation group were significantly lower than the control group (P<0.05).Conclusions:Chemotherapy combined with fluorouracil + cisplatin chemotherapy for advanced esophageal cancer can effectively improve the immune function of patients, reduce the level of tumor markers, inhibit the proliferation of tumor blood vessels, and have significant anti-cancer effects, which is of positive significance for controlling the development of patients' conditions.

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.

Anticancer Drugs (V)─—Synthesis of Etoposide Derivatives

ＡｎｔｉｃａｎｃｅｒＤｒｕｇｓ（Ｖ）─—ＳｙｎｔｈｅｓｉｓｏｆＥｔｏｐｏｓｉｄｅＤｅｒｉｖａｔｉｖｅｓＴＩＡＮＸｕａｎ，ＹＡＮＺｅ－ｑｕｎ，ＬＩＪｉｎ－ｘｉｎａｎｄＣＨＥＮＹａｏ－ｚｕ（ＮａｔｉｏｎａｌＬａｂｏｒａｔｏｒｙｏｆＡｐｐｌｉｅｄＯｒｇａｎ...

Positron emission tomography complete metabolic response as a favorable prog-nostic predictor in esophageal cancer following neoadjuvant chemotherapy with docetaxel/cis-platin/5-fluorouracil

BACKGROUND 18F-fluorodeoxyglucose-positron emission tomography(PET)/computed tomography is useful in diagnosing lymph node and distant metastases of esophageal cancer.However,its value for predicting survival is controversial.AIM To evaluate the value of PET complete metabolic response(CMR)as a prognostic predictor for esophageal cancer.METHODS Between June 2013 and December 2017,58 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy(NAC)in Oita University were enrolled in this retrospective cohort study.Tumors were clinically staged using fluorodeoxyglucose-PET/computed tomography before and after NAC.After NAC,maximal standardized uptake value≤2.5 was defined as PET-CMR,and maximal standardized uptake value>2.5 was defined as non-PET-CMR.We compared short-term outcomes between the PET-CMR group and non-PET-CMR group and evaluated prognostic factors by univariate and multivariate analyses.RESULTS The PET-CMR group included 22 patients,and the non-PET-CMR group included 36 patients.There were no significant differences in intraoperative and post operative complications between the two groups.Five-year relapse-free survival and overall survival in the PET-CMR group were significantly more favorable than those in the non-PET-CMR group(38.6 mo vs 20.8 mo,P=0.021;42.8 mo vs 25.1 mo,P=0.011,respectively).PET-CMR was a significant prognostic factor in terms of relapse-free survival by univariate analysis(hazard ratio:2.523;95%confidence interval:1.034–7.063;P<0.041).Particularly,PET-computed tomography negative N was an independent prognostic factor of relapse-free survival and overall survival by multivariate analysis.CONCLUSION PET-CMR after NAC is considered a favorable prognostic factor for esophageal cancer.Evaluation by PET-computed tomography could be useful in clinical decision making for esophageal cancer.

沙利度胺抑制卵巢癌细胞株SKOV3体外生长机制的研究

目的:探讨沙利度胺(Thal)单药及联合顺铂(cDDP)、5-氟尿嘧啶(5-FU)、依托泊苷(VP-16)对卵巢癌细胞株SKOV3体外增殖的抑制作用。方法:(1)MTT法检测细胞增殖抑制;(2)流式细胞术检测细胞周期;(3)半定量RT-PCR检测血管内皮生长因子(VEGF) mRNA、过氧化物酶体增殖物激活受体γ(PPAR-γ) mRNA的表达。结果:(1)MTT法示Thal单药及联合用药对细胞增殖有抑制作用,且呈浓度和时间依赖性。(2)流式细胞术示Thal能阻滞细胞于G0/G1期,联合用药可增强cDDP、5-FU、VP-16的疗效,显著阻滞细胞于S期。(3)半定量RT-PCR示200、100、50μg/mLThal能抑制VEGF mRNA表达;所有浓度Thal均不影响PPAR-γ mRNA的表达。结论:Thal可抑制卵巢癌细胞株SKOV3体外增殖、阻滞细胞周期、抑制VEGF mRNA表达,联合用药可增强cDDP、5-FU、VP-16的疗效。

中低剂量醛氢叶酸与氟脲嘧啶联合化疗临床观察比较

目的 对比中低剂量醛氢叶酸 (CF)与氟脲嘧啶 ( 5 Fu)联合化疗的近期疗效和毒副反应。同时比较PLF与ELF两方案的疗效和毒性反应。方法 随机采用不同剂量CF/5 Fu +顺铂 (DDP)或足叶乙甙 (VP16)联合化疗方案治疗恶性肿瘤 117例。结果 中、低剂量CF联合化疗有效率分别为 38.0 %和 44.7%(P >0 .0 5 ) ,两组主要毒性反应均以白细胞减少、恶心呕吐、口腔炎和脱发为主 ,均无显著性差异。PLF与ELF方案的有效率分别为 44.0 %和 31.8%(P >0 .0 5 ) ,毒副反应亦为骨髓抑制、恶心呕吐及口腔炎 ,其Ⅲ～Ⅳ级白细胞减少、血小板减少和口腔炎的发生率分别为 11.4%与 44.3%、0 .9%与 5 .6 %及 3.9%与 11.1%(P <0 .0 5 ) ,有统计学差异。结论 低剂量CF与 5 Fu +DDP联合化疗是治疗鼻咽癌和胃肠道癌比较安全、有效、经济的化疗方案。

EAP/LF交替方案治疗进展期胃癌的临床研究

目的:探讨EAP/LF交替方案治疗进展期胃癌的疗效。方法:自1994年10月至1999年12月,124例经病理确诊的有可测量病灶的进展期胃癌患者被随机分入EAP/LF组(研究组)和EAP组(对照组),研究组用药为:足叶乙甙(Vp-16)70mg/m2,静滴,d4-6;阿霉素(ADM)15mg/m2,静注,d1,7;顺铂(DDP)20mg/m2,静滴,d2,8;醛氢叶酸(CF)70mg/m2,静滴,d29-33;5-氟尿嘧啶(5-FU)325mg/m2,静滴,d29-33;每8周重复。对照组用药为:Vp-1670mg/m2,静滴,d4-6,d25-27;ADM15mg/m2,静注,d1,7,22,28;DDP30mg/m2,静滴,d2,8,23,29;每8周重复。结果:研究组客观有效率为62.1%,明显优于对照组的48.3%(P=0.032);研究组有效者中位生存期、无进展生存时间分别为20个月、13个月,均明显优于对照组的13个月(P=0.037)、7个月(P=0.007)。两组不良反应主要有白细胞减少、口腔粘膜炎、脱发。结论:调整剂量的EAP/LF交替方案是一疗效确切、安全、对生存有益处的治疗进展期胃癌的优势方案,值得临床进一步研究。

A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy

Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy.Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benef it from this local-regional approach for prevention and treatment of carcinomatosis.This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology.

Antiproliferation and apoptosis induction of paeonol in HepG_2 cells

AIM： To investigate the antiproliferative effect of paeonol （Pae） used alone or in combination with chemotherapeutic agents [cisplatin （CDDP）, doxorubicin （DOX） and 5-fluorouracil （5-FU）] on human hepatoma cell line HepG2 and the possible mechanisms. METHODS： The cytotoxic effect of drugs on HepG2 cells was measured by 3-（4, 5-dimethylthiazol-2- yl）-2, 5-diphenyltetra-zolium bromide （MTT） assay. Morphologic changes were observed by acridine orange （AO） fuorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry （FCM）. Drug-drug interactions were analyzed by the coefficient of drug RESULTS： Pae （7.81-250 mg/L） had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of （104.77±7.28） mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae （15.63, 31.25, 62.5 rag/L） was combined with CDDP （0.31-2.5 mg/L）, DOX （0.16-1.25 mg/L）, or 5-FU （12.5-100 mg/L） at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae （P 〈 0.01）. Of the three different combinations, the sensitivity of cells to drugs was considerably different.CONCLUSION： Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2, which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.

Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects

Chemotherapy-induced diarrhoea (CID) is a common side-effect experienced by patients being treated with a variety of antineoplastic agents. Approximately 80% of patients undergoing chemotherapeutic treatment for colorectal and other gastrointestinal cancers present with CID;moreover, about 5% of early deaths associated with combination anti-cancer chemotherapy are due to CID. Chronic post-treatment diarrhoea amongst cancer survivors can persist for more than 10 years greatly effecting long-term quality of life. Gastrointestinal toxicities such as diarrhoea and vomiting are amongst the primary contributors to dose reductions and delays throughout anti-cancer treatment, presenting a significant hurdle in clinical management of anti-cancer regimes and often result in sub-optimum treatment. However, little is known about pathophysiological mechanisms underlying CID. This work provides a review of chemotherapy-induced diarrhoea, current management guidelines, and shortcomings of current treatments as well as emerging and already existing anti-diarrhoeal treatments potentially suitable for CID.

Design, Synthesis and Biological Evaluation of Novel Etoposide Analogues as Cytotoxic Agents

Five novel compounds composed of etoposide and 5-fluorouracil derivatives joined by an ester linkage were prepared and evaluated for their antitumor potential. Most of these analogues have exhibited promising in vitro cytotoxic activity against cell cultures of murine leukaemia P-388 and human lung carcinoma A-549. The results presented herein challenged the long-standing structure-activity relationships, which proposed that a free 4＇-hydroxyl group is essential structural requirement for etoposide-like activity. And in addition, the 4＇-position was suggested to tolerate chemical modifications such as esterification. The preliminary testing results also indicated that the design and synthesis of these compounds were beneficial for therapeutic values of etoposide.

Therapeutic Outcomes of HPV Positive and HPV Negative Oropharyngeal Squamous Cell Carcinomas

Background & Objectives: HPV associated (HPV+) oropharyngeal cancers, compared with HPV non-associated ones (HPV?) have different characters and significantly better outcomes. HPV and cancer characteristics differ among countries and few data is available in Indian population regarding this issue. Thus, we attempted to determine the treatment response and survival rates between HPV+ versus HPV negative oropharyngeal cancers in Indian population. Methods: This prospective observational study was conducted from December 2016 - October 2018 in patients with stage III/IV oropharyngeal squamous cell carcinomas (SCC) (n = 65). The patients received induction chemotherapy with Docetaxel, Cisplatin, 5-Fluorouracil × 3 cycles, followed by concurrent chemoradiation 66 Gy as 33 fractions along with cisplatin 40 mg/m2 weekly. The primary outcome was treatment response rate, which was defined as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Secondary outcomes were clinico-pathological differences between two groups, overall survival (OS), progression free survival (PFS). Results: Of the 65 patients included in the study, 17 were HPV positive and 48 patients were HPV negative. Median age in HPV positive arm is 48 years and HPV negative arm is 59 years. HPV positive patients presented with early T stage and advanced nodal (N) stage. Most common histopathology in both arms was moderately differentiated squamous cell carcinomas followed by well differentiated squamous cell carcinomas. HPV+ vs HPV? showed the following, treatment response 82.4% vs 52.1% (p-0.029). 1 year progression free survival (PFS) of 76.5% vs 52.1% in HPV negative arm (p-0.08) & 1 year overall survival was 82.4% vs 70.8% (p-0.353). Grade 3 or 4 toxicities did not differ significantly between HPV positive and HPV negative arms. Conclusion: HPV positive oropharyngeal SCC patients showed significantly better treatment response than HPV negative ones. Progression free survival, overall survival and toxicity profile did not differ significantly between the two groups. Although due to small size, we did not compare data stratified by the cancer characteristics, the data is worthy to further characterize this tumour especially as HPV positive versus HPV negative.