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.

Etoposide-based Combination Chemotherapy in Malignant Histiocytosis

We investigated the responses of patients with malignant histiocytosis (MH) to the treatment of epotoside-based regimen.Of 11 evaluable cases,9(81. 8%)achieved complete remission and 1 partial remission.7 complete remission cases (77. 7%) received only one therapeutic course.The side effects were mild and welltolerated. We conclude that etoposide-containing regimen is highly effective and can be used as first-line treatment for MH and is worthy of further study.

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

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

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.

Docetaxel and cisplatin combination chemotherapy in anthracyclines-resistant advanced breast cancer

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.

Gemcitabine and oxaliplatin combination chemotherapy in 30 patients with advanced pancreatic carcinoma

Objective: To evaluate the activity and safety of combination chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen) in patients of advanced pancreatic carcinoma. Methods: 30 patients with advanced pancreatic cancer were enrolled into this study. All patients received gemcitabine 1000 mg/m2, given by 30-minute intravenous infusion, on days 1 and 8 of each 21-day cycle. Oxaliplatin 100 mg/m2 was administered as a 2 h infusion on day 1 of each 21 day. Clinical outcomes for patients treated with two cycles of chemotherapy were evaluated according to WHO criteria. Results: All 30 patients were eligible for effectiveness and safety analysis. Objective response rate was approximately 20.0%. Clinical benefit response (CBR) was a composite of assessment of pain, performance status and body weight. The pain relief rate, improve-ment rate of performance status and body weight were 53.3%, 46.7% and 36.7%, respectively. The main adverse effects were bone marrow depression, peripheral nerve toxicity and gastrointestinal reaction. There was no treatment-related death during the chemotherapy. Conclusion: The high response rate with low toxicity observed in this study suggests that GEMOX regimen may be an effective alternative curative treatment for patients with advanced pancreatic carcinoma and can be used more extensively in clinical practice.

Self-Motivated Supramolecular Combination Chemotherapy for Overcoming Drug Resistance Based on Acid-Activated Competition of Host–Guest Interactions

In this work,we propose a nanoparticle-based strategy of self-motivated supramolecular combination chemotherapy that carries drugs stably and releases them actively in the acidic tumor microenvironment to overcome the drug resistance of cancer cells.This self-motivated nanoparticle consists of a cucurbit[7]uril-containing polymer(PCB)-based core.

PHASE II CLINICAL TRIAL OF LASTET CAPSULE IN COMBINATION CHEMOTHERAPY OF MALIGNANT TUMORSIN CHINA

This study reports the efficacy of prolonged administration of oral etoposide in the treatment of 86 cases with solid tumor,malignant lymphoma and other cancer.The oral etoposide used was the Lastet capsule (Las-c).An overall response rate(RR)of 62.8% was achieved with CR rate being 23.3% and PR rate 39.5%. Different combination chemotherapy regimens led to different response rates but no significant difference was found. The Las-C containing regimens used in this study have not caused any serious side effects.

A bicistronic retroviral vector to introduce drug resistance genes into human umbilical cord blood CD34^+ cells to improve combination chemotherapy tolerance

OBJECTIVE: To study whether human umbilical cord blood CD34+ cells transduced with human aldehyde dehydrogenase class-1 (ALDH-1) and multidrug resistance gene (MDR1) have increases resistance to 4-Hydroperoxycyclo-phosphamide (4-HC) and P-glycoprotein effluxed drugs. METHODS: A bicistronic retroviral vector G1Na-ALDH1-IRES-MDR1 was constructed and used to transfect the packaging cell lines GP + E86 and PA317 by LipofectAMINE method, using the medium containing VCR and 4-HC agents for cloning selection and ping-ponging supernatant infection between the ecotropic producer clone and the amphotropic producer clone, we obtained high titer amphotropic PA317 producing cells with high titers up to 5.6 x 10(5) CFU/ml. Cord blood CD34+ cells were transfected repeatedly with supernatant of retrovirus containing human ALDH-1 and MDR1cDNA under the stimulation of hemopoietic growth factors. RESULTS: Bicistronic retroviral vector construction was verified by restriction endonuclease analysis. Polymerase chain reaction (PCR), reverse transcription (RT)-PCR, Southern blot, Northern blot, fluorescenceactivated cell sorting (FACS) method and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analyses showed that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgenes recipient cells confered 4-fold stronger resistance to 4-HC and 5.5 to 7.2-fold P-glycoprotein effluxed drug than untransduced cells. CONCLUSION: The bicistronic retroviral vector-mediated transfer of two different types of drug resistance genes into human cord blood CD34+ cells and co-expression provided an experimental foundation for improving combination chemotherapy tolerance in tumor clinical trial.

The short-time effects of chemotherapy with combinations of hydroxycamptothecine and oxaliplatin in treatment of advanced colorectal cancer

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.

Using Pegaspargase in Combination with Chemotherapy in the Treatment of Lymphoma

Objective:To analyze the clinical effect of pegaspargase combined with chemotherapy on patients with lymphoma.Methods:Seventy patients with lymphoma admitted to Shaanxi Provincial People’s Hospital between December 2020 and June 2021 were selected as study subjects and were equally divided into the control group and the intervention group using the lottery method,with 35 cases in each group;the control group received conventional treatment,while the intervention group received pegaspargase combined with chemotherapy.The treatment satisfaction,quality of life,psychological status,and incidence of adverse reactions of the patients in the two groups were compared.Results:The differences in the indicators between the two groups were statistically significant(p<0.05).Conclusion:Pegaspargase combined with chemotherapy can effectively improve the treatment effect and satisfaction of lymphoma patients;hence,it is worthy of promotion in clinical treatment.

Pneumatosis Cystoides Intestinalis Complicated during Chemotherapy for Pulmonary Nontuberculous Mycobacterial Disease

Background: Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of gas in the intestinal wall. Aim: We report two rare cases of PCI that are complicated during the chemotherapy for pulmonary nontuberculous mycobacterial (NTM) disease. Case Presentation: In this report, we described two cases (a 72-year-old woman and a 60-year-old woman) of PCI that appeared during the combined chemotherapy consisting of rifampicin, ethambutol and clarithromycin. Because there were few clinical symptoms and increased inflammatory responses, the diagnosis of PCI was delayed. However, there were fortunately no severe complications in both cases. Conclusion: Respiratory physicians should be aware of the potential development of PCI in patients during the chemotherapy for pulmonary NTM disease. It is important to detect PCI in the early stage through radiological examinations to avoid severe complications.

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.

Systemic chemotherapy for metastatic breast cancer

Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer （MBC）. Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metasta- sis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combi- nation agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel- bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and catuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall sur- vival with maintenance chemotherapy according to a Korean phase III clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy （X-based X） appears favorable based on a series of domestic studies.

Evaluation of the Efficiency of the Magicramp® Device for Reducing Cramps Resulting from Oncological Treatments: “Double-Blind, Randomized Clinical Trial”

We identified that oncological treatments in general (chemotherapies, immunotherapies and radiotherapies) frequently cause peripheral neuropathy, including cramps, characterized by excess protons due to metabolic and neuronal factors, such as sudden changes in pH, uremia and aspects that affect neuromotor functions. Such situations and others like them are often neglected in treatment, which naturally concerns itself with the main problem: Cancer. Sometimes toxic solutions are implemented that have comorbid side effects, such as duloxetine (standard treatment). Based on monitoring of cancer patients who used the non-toxic product, called “Magicramp® Electrostatic Charge Reduction Cushion” (MECRC), approved in Europe more than 10 years ago, we carried out a controlled test in Brazil. In this clinical trial, we hypothesized that reducing excessive ionic charges (electrostatic charge), which is one of the side effects often described in the literature as “Chemotherapy-Induced Peripheral Neuropathy” (CIPN), would decrease or eliminate cramping, under the hypothesis that such elimination would prevent or attenuate muscular vulnerability to action impulses, and increase the power of relaxation through the same mechanism. In this double-blind and randomized clinical trial, 40 (forty) adult patients with muscle cramps caused by oncological treatments were tested, evaluating the degree of efficiency of the product that aims to reduce muscle cramps, by eliminating and/or reducing excess loads electrostatic ionic. Data from the clinical research conducted in this study are available online at https://doi.org/10.7910/DVN/QUS94U.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma

INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

Point injection of Injectio Radici Astragali for Treatment of Post-chemotherapy Adverse Reactions

With injection of Injectio Radici Astragli into the point Zusanli (ST 36), we have obtained quite satisfactory therapeutic results for treating leukopenia and the impairment in immune functions occurred in cancer chemotherapy. A report follows.

Treatment of Interstitial Peumopathy by Fei Tong Oral Liquid in the Malignant Tumor Patients after Radio-and/or Chemotherapy

Fei Tong Kou Fu Ye (肺通口服液 Fei Tong Oral Liquid) was used to treat 30 cases of interstitial pneumopathy after radio- and/or chemotherapy.In comparison with the control group (15 cases) treated with hormones,the therapeutic effects in improving dyspnea,cough,respiratory rate,cyanosis,findings in X-films and CT examination,partial pressure of oxygen in artery,FVC and VC were found significantly better (P<0.05).The total effective rate obtained was 83.33%.