Vorolanib,an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors:An open-label,phaseⅠdose escalation and dose expansion trial

Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.

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.

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.

Predictive Value of Body Composition Analysis for the Prognosis of Patients with Advanced Gastrointestinal Tumors

Objective There is strong evidence that the body composition can affect the progression-free survival(PFS)and overall survival(OS)in patients with a variety of cancers.The main objective of this study was to investigate the effect of body composition on the prognosis of patients with advanced gastrointestinal and colorectal cancers who received first-line palliative chemotherapy.Methods Patients who were newly-diagnosed with advanced gastrointestinal or colorectal cancer and received standard first-line palliative chemotherapy from January 2017 to December 2018 were included in this retrospective study.An analysis of computed tomography images was performed to determine the skeletal muscle index(SMI),which reflects the skeletal muscle mass and skeletal muscle density(SMD)related to muscle strength.A Kaplan-Meier survival analysis and log-rank test were used to compare the survival relationships among groups stratified by the SMI,and a Cox proportional hazard model was used for a multivariate analysis.Results A total of 108 patients met the inclusion criteria,including 41 cases of gastric cancer,46 cases of left colorectal cancer,and 21 cases of right colon cancer.In patients with gastric cancer,the OS of women was significantly shorter than that of men.The OS of patients with a low SMI,low SMD,and low phase angle(PA)was significantly shorter than that of patients with high values(P≤0.05).In the multivariate analysis,the SMD was significantly associated with the patients'long-term survival[Hazard Ratio(HR)=0.904,95%CI:0.840~0.974,P=0.008].For patients with a low SMI and PA,the PFS was significantly shorter than that of patients with high values(P≤0.05).In patients with left colon cancer,the PA and SMD were both independent risk factors for a poorer long-term prognosis(HR=0.375,95%CI:=0.167~0.840,P=0.017;HR=0.887,95%CI:0.824~0.954,P=0.001).Among right colon cancer patients,the PFS and OS of those with a low SMD were significantly lower than those for patients with high values(P≤0.05).Conclusion The PA is an independent risk factor for the OS of left colon cancer patients;the SMD is an independent risk factor for the survival of patients with gastric cancer,left colon cancer,and right colon cancer.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Progression of targeted therapy in advanced cholangiocarcinoma

It is necessary to establish an effective therapy to improve the survival of patients with advanced eholangiocarcinoma （CCM. Recently, with the development of pathology research in CCA, a lot of special bio-markers such as EGFR, VEGF, HER2, and MEK et al. could be over expression or mutations in CCA patients. According to their changes, combinations of targeted therapy plus chemotherapy are now recognized as effective therapies for advanced CCA. The aim of this paper is to analyze recent promising studies about targeted therapy alone or combination with each other or with chemotherapies.

Cancer Pain with Standardized Nursing

Background: The incidence of cancer pain in patients with malignant tumors is relatively high, and pain control is poor, which is closely related to many factors, especially the nursing way. Objective: To explore the effect of standardized nursing model on pain control in patients with malignant tumors. Methods: 50 patients with malignant tumors treated in the Affiliated Hospital of Chengde Medical College from January to December in 2021 were randomly divided into 25 cases in the control group and 25 cases in the observation group. The pain control and medication compliance of the two groups were compared. Results: There was no difference in the corresponding score of admission pain between the two groups (P > 0.05), and the pain score of the observation group was lower than that of the control group (P P Conclusion: Standardized cancer pain nursing can ease the pain of patients, and the medication compliance is better.

An open-labeled, randomized, multicenter phase Ⅱa study of gambogic acid injection for advanced malignant tumors

Background Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge （Garcinia morella Desv.）. Based on the preliminary results of a phase I study, this phase Ila study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors. Methods Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m2 gambogic acid intravenously from Days 1 to 5 of a 2-week cycle （Group A）, or 45 mg/m2 every other day for a total of five times during a 2-week cycle （Group B）. The primary endpoint was objective response rate （ORR）. Results Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates （DCRs） were 76.2% in Group A and 61.5% in Group B （P=0.0456）. The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms. Conclusions The preliminary results of this phase Ila exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m2. The DCR was greater in patients receiving gambogic acid on Days 1-5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

Craniofacial resection of advanced oral and maxillofacial malignant tumors

Objective To evaluate the clinical outcome of craniofacial resection for advanced malignant tumors in oral and maxillofacial regions.Methods Forty-six patients who underwent craniofacial resection for malignancies involving the anterior and middle cranial fossa over a 20-year period between June 1978 and December 1997 at our department were evaluated. Twenty patients received radiation therapy and an adjuvant therapy after the operation. Eleven patients received chemotherapy of various types as an adjuvant therapy.Results The 3- and 5-year survival rates were 48.8% (20/41) and 35.1% (13/37), respectively, while the 10-year survival rate was 20% (4/20).Conclusions Our results revealed good prospects of using craniofacial resection on patients with advanced malignancies in the oral and maxillofacial regions.

Advances in medical treatment for pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.

A NEW EXPERIMENTAL AND CLINICAL APPROACH OF COMBINING USAGE OF HIGHLY ACTIVE TUMOR-INFILTRATING LYMPHOCYTES AND HIGHLY SENSITIVE ANTITUMOR DRUGS FOR THE ADVANCED MALIGNANT TUMOR

In recent years, tumor-nfiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach a. cold digestion with collagenase at 4C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-old was greater than that with the original approach. Cytotoxicity against rumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL / IL2, LAK / 1L2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.

Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers

Aim:Primary tumors can be divided into oncogene-addicted(e.g.,lung)and non-oncogene addicted(e.g.,breast).Only the former group has an Achilles-heel single gene for successful target therapy,whereas the latter has mutations of multiple causative genes.Currently,tissue biopsy used for genetic surveys do not give a complete picture of the molecular profile and clonal evolution,but only provide static information over time.Methods:A series of 133 patients with 16 different solid tumors were enrolled.Blood samples were collected and cell-free DNA(cfDNA)was extracted.cfDNA libraries were analyzed using AVENIO circulating tumor DNA(ctDNA)Expanded Kit and Illumina NextSeq 550 for sequencing was used.In order to evaluate the clinical evolution over time,a second cfDNA analysis was performed after a mean interval of 2 months.Results:Through the cfDNA liquid biopsy,we found 89 pathogenic variants in 54 genes.Breast,lung,and prostate cancers showed the largest number of mutated genes.TP53,PIK3CA,FGFR3,KRAS,and ERBB2 were the most frequently mutated genes among 16 different tumors.Gene distribution didn’t show any type of prevalence.In particular,every patient with disease progression seems to have a“private”combination of gene pair mutations,with TP53 as the most frequently mutated gene.Conclusion:We showed that the clonal evolution of tumors includes a private combination of genes,regardless of tumor type.In the future,the cancer treatment can be the targeted therapy against specific tumor mutation(s).The present approach seems promising to both identify key cancer genes and follow clonal evolution over time.

Clinical Study on Effect of Kang'aibao Oral Liquid(抗癌宝口服液) in Treating 103 Patients of Malignant Tumor

Objective: To observe the clinical efficacy of Kang'aibao oral liquid (KABL), a Chinese herbal preparation in treating malignant tumor of middle or advanced stage. Methods: A comparative study was done by observing the effect of 103 patients treated with KABL, and another 90 patients treated with chemotherapy at the same time were taken as the control group.Results: The immunologic function, short term effective rate (complete relieved rate and partial relieved rate), survival quality, 1 , 2 and 3 year survival rate, median survival time, and carcinoembryonic antigen (CEA) declining rate of the KABL group were significantly higher than those of the control group. Conclusion: KABL has the effects of inhibiting tumor growth, prolonging survival time and improving survival quality of tumor patients.