Discussion on gemcitabine combined with targeted drugs in the treatment of pancreatic cancer

Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemic therapy(chemotherapy,targeted therapy and immunotherapy).We read with great interest the review“Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment”published on World J Gastroenterol and intended to share some of our perspectives in pancreatic cancer treatment.This review presents the therapeutic effects of the combination of gemcitabine and targeted drugs,which gives us a deeper insight into the combination treatments for pancreatic cancer.

Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

VARIOUS DOSES OF CISPLATIN (DDP) COMBINED WITH MULTI-DRUG CHEMOTHERAPY FOR ADVANCED MALIGNANT SOLID TUMOR

Two hundred and thirty-six patinets with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: (1) 20 ing/day×4- 5, 80 cases; (2) 30 mg day × 3 - 5, 91 cases; (3) 40 mg/ day 3 -4, 37 cases; (4) 50 mg/day×2 - 3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR+PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). Ths response rate was lower than that of group 30 mg, 40 mg, and 50 mg 43.4% and 50%) (P<0.05). The remissions in various groups were not significantly different.The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppresion was less in single DDP group than that of combined chemotherapy group (P<0.05), DDP 30-50 mg 1/d×5-3 was better than HD-DDP in some patients.

Clinical Observation of Arteriovenous Combined Chemotherapy in Advanced Gastric Cancer

Objective:To analyze the therapeutic effect and influencing factors of arteriovenous combined chemotherapy in 39 patients with advanced gastric cancer,and to explore the choice of therapeutic strategy.Methods:In this group of patients,the sequence of combined use of arteriovenous chemotherapy was 2 cycles of arterial chemotherapy first,followed by 3~4 cycles of systemic intravenous chemotherapy,and then changed to traditional Chinese medicine,oral chemotherapeutic drugs or immunotherapy after stable disease.Results:Thirty-five patients achieved complete disappearance of symptoms,significant tumor reduction of 26%(PR:13/39),moderate tumor reduction of 51%,18 patients with tumor markers decreased by more than 50%,4 patients completely reduced to normal,half-year survival rate of 90%,1-year survival rate of 56%,3-year survival rate of 33%,5-year survival rate of 10%.Conclusion:The use of arteriovenous combined chemotherapy and embolization in patients with middle and advanced gastric cancer is not only feasible,but also less complications.It can enable some patients to achieve stage II surgical resection,reduce or delay the metastasis and recurrence of patients,improve the quality of life of patients and prolong the survival time.

Photothermal and Chemotherapy Combined Therapy of B-CuS-DOX Based on/pH Dual Stimulation

Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.

Effect of Astragalus Injection Combined with Chemotherapy on Qual ity of Life in Patients with Advanced Non-small Cell Lung Cancer

Objective: To observe the effect of Astragalus injection (AI) combined with chemotherapy on quality of life (QOF) in patients with advanced non-small cell lung caner (NSCLC). Methods: Sixty NSCLC patients were randomly divided into the treated group (n=30,treated with AI combined with chemotherapy) and the control group (n=30, treated with chemotherapy alone). Chemotherapy of MVP protocol was applied to both groups. AI was supplemented to the treated group by intravenous dripping 60 ml per day. Treatment of 21-28 days consisted one treatment cycle, and 2-3 cycles were applied. WResults: The effective rate in the treated group was 40.0% and in the control group was 36.7%, the mean remission rate in them being 5.4 month s and 3.3 months, the median survival period 11 month and 7 month and the 1-year survival rate 46.75% and 30.0%, respectively, the difference of these indexes between the two groups were all significant (P<0 05). Moreover, the clinical improving rate and QOF elevation rate in the treated group was 80.4% and 43.3%, as compared with those in the control group (50.0% and 23.3% respectively), the different was also significant (P<0 01). Conclusion: AI combined with chemotherapy can significantly improve the QOF in NSCLC patients of advanced stage.

Time-dependent study of combined chemotherapy of Cyclophophamide,Cisplatin and Adriamycin

Objective This paper was aimed to investigate the time-dependence of toxicity and pharmacodynamic action in Cyclophosphamide-Cisplatin-Adriamycin(CAP)combined chemotherapy and to find theoptimal administrating time to provide the better dosage regimen for the clinical cancer treatment.Methods S180 tumor bearing mice were firstly divided into six groups,and then were injected(ip.)with CTX(20 mg·kg-1),DDP(1 mg·kg-1),ADM(1 mg·kg-1)at different time(10:00 h,14:00 h,18:00 h,22:00 h,02:00 h and 06:00 h),respectively.In all groups ADM(1 mg·kg-1)were administed every three days.Finally the various related data was collected to assess the time-dependence of toxicity and pharmacodynamic action in CAP combined chemotherapy.Results The tumors could be inhibited by CAP combined chemotherapy in all the tested groups at different time,the group administed at 02:00 h showed the best action.The results of tumor cell cycle analysis showed that DNA synthesis decreased after the chemotherapy,most significantly at 22:00 h.The levels of tumor cell apoptosis-related proteins p53 and Bcl-2 increased after combination chemotherapy,whereas the level of Bax declined.And p53 changed most remarkably from 18:00 to 22:00 h,and for Bcl-2 and Bax that was from 02:00 to 10:00 h.The distribution of bone marrow cells cycle appeared sub-G1 peak,which is the phenomenon of apoptosis,at 02:00 h and 10:00 h was the most significant.At the same time the proportion of G1 and S-phase decreced,which indicates DNA synthesis of bone marrow cell declined.A time-dependent 19 KD activated fragments of Caspase-3 appeared by western blotting determination,at 02:00 h and 10:00 h.Conclusions The CAP combined chemotherapy had the best pharmacodynamic action during 22:00-02:00 h and the worst during the 10:00-14:00 h.As refer to toxicity,the most toxic time was during 06:00-14:00 h.

The Clinical Study of Multigene Combination Test to Guide Chemotherapy Combined with Targeted Therapy in Patients with Advanced Gastrointestinal Tumors

Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective： To investigate the inhibitory effects of combination chemotherapy of Carboplatin （CBP）, Teniposide （Vm-26）, Methasquin （MTX）, and Nimodipine （NIM） on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods： MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP＋NIM, Vm-26＋NIM, MTX＋NIM, CBP＋Vm-26＋MTX, or CBP＋Vm-26＋MTX＋NIM, respectively. Results： The inhibition rate of CBP＋Vm-26＋MTX＋NIM combination administration against glioma cells was 96.64%, higher than that of CBP＋NIM （69.03%）, Vm-26＋NIM （71.53%）, MTX＋NIM （52.75%）, CBP＋Vm-26＋MTX （78.59%） （P〈0.01）, and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion： The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

NIR-IIb-triggered photodynamic therapy combined with chemotherapy platform based on rare-earth-doped nanoparticles

Photodynamic therapy(PDT),with high spatiotemporal selectivity,minimal side effects and less drug resistance,has emerged as a promising approach for the treatment of cancer.However,inadequate penetration depth and poor efficacy seriously restrict its practical application.To address these challenges,we developed a combined therapy platform(RENP@C/D-FA)based on rare-earth-doped nanoparticles(RENPs)with a structure of NaErF_(4):Tm(0.5%)@NaYF_(4),on which photosensitizer Ce6(chlorin e6)and chemo-therapeutic drug(DOX)(doxorubicin)were loaded by encapsulating with an amphiphilic polymer distearoyl phosphatidylethanolamine-polyethylene glycol-folic acid(DSPE-PEG-FA).RENPs with NaErF_(4) as the matrix possess multiple excitation/emission peaks,enabling activation of PDT under near-infrared-Ⅱb(NIR-Ⅱb,1500-1700 nm)excitation and luminescence imaging in NIR-Ⅱb region by absorbing 808 nm near-infrared photons.Furthermore,DOX can be selectively released in the acidic microenvironment of tumors.Benefiting from the tumor targeting capability of folic acid,this platform can successfully ablate tumor cells and inhibit tumor growth by combining PDT and chemotherapy.This innovative approach holds great promise as a powerful tool for cancer treatment,showing the potential to revolutionize PDT.

Combination therapy for scalp angiosarcoma using bevacizumab and chemotherapy: a case report and review of literature

Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma. The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited. The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro

AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met(-)Hcy(+)) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met(-)Hcy(+) was suppressed, manifested by the decrease of total cell counts [1.46 +/- 0.42 (x 10(9).L(-1)) in Met(-)Hcy(+) vs 1.64 +/-0.44(x 10(9).L(-1)) in Met(+)Hcy(-), P【0.01], the decline in the percentage of G(0)G(1) phase cells (0.69 +/- 0.24 in Met(-)Hcy(+) vs 0.80 +/- 0.18 in Met(+)Hcy(-), P【0.01) and the increase of S cells (0.24 +/- 0.20 in Met(-)Hcy(+) vs 0.17 +/- 0.16 in Met(+)Hcy(-), P【0.01); however, gastric mucosal cells grew normally. If Met(-)Hcy(+) medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer cells dropped significantly. CONCLUSION: Human primary gastric cancer cells in vitro are Met-dependent; however, gastric mucosal cells have not shown the same characteristics. Met(-)Hcy(+) environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells.

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.

Clinical progression of lobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer

The platinum-based combination chemotherapy has become one of the major modalities in anti-cancer treatment. After the first-line chemotherapy, many patients need further chemotherapy because of recurrence or metastasis. Lobaplatin is one of the third generation platinum drugs,and this article briefly reviews the clinical progression of Iobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer.