2.Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study.
Li ZHANG ; Ji Fang GONG ; Hong Ming PAN ; Yu Xian BAI ; Tian Shu LIU ; Ying CHENG ; Ya Chi CHEN ; Jia Ying HUANG ; Ting Ting XU ; Fei Jiao GE ; Wan Ling HSU ; Jia SHI ; Xi Chun HU ; Lin SHEN
Journal of Peking University(Health Sciences) 2022;54(5):971-980
		                        		
		                        			OBJECTIVE:
		                        			To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).
		                        		
		                        			METHODS:
		                        			This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC).
		                        		
		                        			RESULTS:
		                        			This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified.
		                        		
		                        			CONCLUSION
		                        			Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Antibodies, Monoclonal, Humanized
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular/drug therapy*
		                        			;
		                        		
		                        			Cisplatin/therapeutic use*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Liver Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Lung Neoplasms/pathology*
		                        			;
		                        		
		                        			Nasopharyngeal Neoplasms/drug therapy*
		                        			
		                        		
		                        	
4.Clinical Study of Chemotherapy Combined with Antivirals for Adult T-cell Leukemia/Lymphoma.
Ying LIN ; Rong-Dong ZHANG ; Ren-Li CHEN ; Jie CHEN ; Ying WU ; Qi CHEN
Journal of Experimental Hematology 2022;30(5):1407-1414
		                        		
		                        			OBJECTIVE:
		                        			To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors.
		                        		
		                        			METHODS:
		                        			Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed.
		                        		
		                        			RESULTS:
		                        			The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)% and (40.9±2.1)% (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)% and (13.6±2.8)% (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy [HR=5.617 (95%CI 1.803-11.293), P=0.027] were independent prognostic factors for the long-term efficacy.
		                        		
		                        			CONCLUSION
		                        			Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Antiviral Agents/therapeutic use*
		                        			;
		                        		
		                        			Cyclophosphamide
		                        			;
		                        		
		                        			Doxorubicin
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interferon alpha-2/therapeutic use*
		                        			;
		                        		
		                        			Ki-67 Antigen
		                        			;
		                        		
		                        			Lactate Dehydrogenases
		                        			;
		                        		
		                        			Leukemia-Lymphoma, Adult T-Cell/drug therapy*
		                        			;
		                        		
		                        			Lymphoma/drug therapy*
		                        			;
		                        		
		                        			Oxidoreductases/therapeutic use*
		                        			;
		                        		
		                        			Vincristine/therapeutic use*
		                        			;
		                        		
		                        			Zidovudine/therapeutic use*
		                        			
		                        		
		                        	
5.2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages.
Wen Hua DUAN ; Li Ya JIN ; Zu Chao CAI ; David LIM ; Zhi Hui FENG
Biomedical and Environmental Sciences 2021;34(9):693-704
		                        		
		                        			Objective:
		                        			The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.
		                        		
		                        			Methods:
		                        			Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.
		                        		
		                        			Results:
		                        			The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.
		                        		
		                        			Conclusion
		                        			The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Cell Proliferation/radiation effects*
		                        			;
		                        		
		                        			Combined Modality Therapy
		                        			;
		                        		
		                        			Cytokines/immunology*
		                        			;
		                        		
		                        			Fatty Acids, Unsaturated/therapeutic use*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Mammary Neoplasms, Experimental/radiotherapy*
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Tumor-Associated Macrophages/radiation effects*
		                        			
		                        		
		                        	
6.Radiofrequency deep hyperthermia combined with chemotherapy in the treatment of advanced non-small cell lung cancer.
Wen-Hui YANG ; Jun XIE ; Zhi-Yong LAI ; Mu-Dan YANG ; Ge-Hong ZHANG ; Yuan LI ; Jian-Bing MU ; Jun XU
Chinese Medical Journal 2019;132(8):922-927
		                        		
		                        			BACKGROUND:
		                        			In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion.
		                        		
		                        			METHODS:
		                        			We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant.
		                        		
		                        			RESULTS:
		                        			Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs. 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs. 46.7%, χ = 13.16, P < 0.001) and gastrointestinal (25.0% vs. 77.8%, χ = 25.88, P < 0.001) adverse reactions than that in CT group. The objective tumor response and survival showed no significant differences.
		                        		
		                        			CONCLUSIONS
		                        			Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients. Also, it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Antineoplastic Agents
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Carcinoma, Non-Small-Cell Lung
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			therapy
		                        			;
		                        		
		                        			Cisplatin
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Deoxycytidine
		                        			;
		                        		
		                        			analogs & derivatives
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hyperthermia, Induced
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Lung Neoplasms
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			therapy
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
7.Intracranial involvement in newly diagnosed multiple myeloma with TP53 deletion: Two case reports.
Shuang QU ; Lisheng LIAO ; Ying XIE ; Zhihai ZHENG ; Biyun CHEN
Journal of Central South University(Medical Sciences) 2018;43(11):1272-1275
		                        		
		                        			
		                        			We report two rare cases of multiple myeloma (MM) with dural intracranial disease and TP53 deletion. The two patients presented with skull lytic lesion and dural involvement of myeloma. The association between intracranial involvement in MM and TP53 deletion has not been determined. The two patients received bortezomib-based intensive induction and got good response, just as that reported in literature. MM presenting with dural intracranial disease and TP53 deletion at diagnosis is associated with poor outcome. Multi-drug regime containing bortezomib followed by autologous or allogeneic stem cell transportation would improve the prognosis.
		                        		
		                        		
		                        		
		                        			Antineoplastic Agents
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols
		                        			;
		                        		
		                        			Bortezomib
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Brain Neoplasms
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Gene Deletion
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Multiple Myeloma
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Tumor Suppressor Protein p53
		                        			;
		                        		
		                        			genetics
		                        			
		                        		
		                        	
8.Individualized Comprehensive Therapy for the Lung Cancer Patients with HIV Infection.
Chinese Journal of Lung Cancer 2018;21(4):327-332
		                        		
		                        			BACKGROUND:
		                        			To observe clinical features, clinical stagings, types ofpathology, treatment options and clinical effects of patients suffer from HIV infection combined with lung cancer, and also to provide guidance for individualized comprehensive treatment of HIV combined with lung cancer.
		                        		
		                        			METHODS:
		                        			Through the retrospective analysis of 53 cases of HIV merger of lung cancer patients admitted in our department, 47 cases of non-small cell lung cancer (NSCLC), 6 cases of small cell lung cancer (SCLC), 24 cases accepted surgery combined chemotherapy, 22 patients with simple chemotherapy, 7 cases give up treatment; 28 cases are in stages I-III, 25 cases are in stage IV; 24 patients received combined chemotherapy in 28 patients with stages I-III, 2 cases gave up treatment, 2 cases with severe chronic obstructive pulmonary disease (COPD) could not tolerate chemotherapy plus surgery. According to the situation of patients before highly active anti-retroviral therapy (HAART) treatment, patients who received HAART before treatment were divided into observation group (n=27), patients who did not receive HAART were divided into control group (n=19). The survival and the independent influencing factors between the two groups were analyzed.
		                        		
		                        			RESULTS:
		                        			Among the 53 HIV infected cases a toal of 46 patients received treatment among 53 cases of treatment in patients with lung cancer merger of HIV, there are no differences of 1 year survival rate, 2 years survival rate between observation group and control group; patients in I-III phase 1 year survival rate was 76.0%, 2 years survival rate was 60.0%. Patients in IV phase 1 year survival rate was 13.6%, 2 years survival rate was 0%. 24 patients with surgery combined chemotherapy 1 year survival rate was 83.3%, 2 years survival rate was 62.5%; 22 cases treated with simple chemotherapy 1 year survival rate was 18.0%, 2 years survival rate was 0%.
		                        		
		                        			CONCLUSIONS
		                        			HIV merger in patients with lung cancer can improve the patients survival rate after different individualized comprehensive treatment, early surgery with combined chemotherapy has remarkable effect.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anti-HIV Agents
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Antiretroviral Therapy, Highly Active
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			HIV Infections
		                        			;
		                        		
		                        			complications
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lung Neoplasms
		                        			;
		                        		
		                        			complications
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			surgery
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplasm Staging
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Survival Rate
		                        			
		                        		
		                        	
9.Role of chemotherapy in prostate cancer.
Rita NADER ; Joelle EL AMM ; Jeanny B ARAGON-CHING
Asian Journal of Andrology 2018;20(3):221-229
		                        		
		                        			
		                        			Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.
		                        		
		                        		
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Chemotherapy, Adjuvant
		                        			;
		                        		
		                        			Docetaxel/therapeutic use*
		                        			;
		                        		
		                        			History, 20th Century
		                        			;
		                        		
		                        			History, 21st Century
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Prostatic Neoplasms/surgery*
		                        			;
		                        		
		                        			Taxoids/therapeutic use*
		                        			
		                        		
		                        	
10.Intermittent, low-dose, antiandrogen monotherapy as an alternative therapeutic option for patients with positive surgical margins after radical prostatectomy.
Kyung Hwa CHOI ; Seung Ryeol LEE ; Young Kwon HONG ; Dong Soo PARK
Asian Journal of Andrology 2018;20(3):270-275
		                        		
		                        			
		                        			The aim of the present study was to determine whether oncologic outcomes and adverse events associated with active on/off intermittent antiandrogen monotherapy (daily bicalutamide, 50 mg per day) are comparable with those of standard external beam radiation therapy (EBRT) or combined androgen blockade (CAB) therapy in prostate cancers with positive surgical margins after radical prostatectomy. Two hundred twenty-three patients with positive surgical margins post-radical prostatectomy who underwent active surveillance (AS, n = 32), EBRT without hormone therapy (n = 55), intermittent antiandrogen monotherapy without EBRT (IAAM, n = 50), or CAB without EBRT (n = 86), between 2007 and 2014, were reviewed retrospectively. Pathologic outcomes, biochemical recurrence rates, radiological disease progression, and adverse events were collected from medical records. Biochemical recurrence rates, biochemical recurrence-free survival rates, and radiological recurrence were not different between the groups (P = 0.225, 0.896, and 0.284, respectively). Adverse event rates and severities were lower for IAAM compared with EBRT or CAB (both P < 0.05), but were comparable to those for AS (P = 0.591 and 0.990, respectively). Grade ≥3 adverse events were not reported in the IAAM or AS groups. Erectile dysfunction and loss of libido rates were lower in the IAAM group compared with the EBRT and CAB groups (P = 0.032). Gastrointestinal complications were more frequently reported in the EBRT group (P = 0.008). Active on/off IAAM treatment might be an appropriate treatment option for patients with positive surgical margins after radical prostatectomy. Furthermore, regarding oncologic outcomes, IAAM was comparable to standard EBRT but had a milder adverse event profile.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Androgen Antagonists/adverse effects*
		                        			;
		                        		
		                        			Anilides/adverse effects*
		                        			;
		                        		
		                        			Antineoplastic Agents/adverse effects*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Chemotherapy, Adjuvant/adverse effects*
		                        			;
		                        		
		                        			Disease-Free Survival
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/blood*
		                        			;
		                        		
		                        			Neoplasm, Residual
		                        			;
		                        		
		                        			Nitriles/adverse effects*
		                        			;
		                        		
		                        			Prostate-Specific Antigen/blood*
		                        			;
		                        		
		                        			Prostatectomy
		                        			;
		                        		
		                        			Prostatic Neoplasms/therapy*
		                        			;
		                        		
		                        			Radiotherapy, Adjuvant/adverse effects*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Tosyl Compounds/adverse effects*
		                        			
		                        		
		                        	
            
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