Humans ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.
Humans ; China ; Physicians ; Antineoplastic Agents/therapeutic use*

OBJECTIVETo observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.

METHODSFrom March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.

RESULTSAmong 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.

CONCLUSIONThe combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.

Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Oxides ; therapeutic use

Antibody-drug conjugate (ADC) is a type of targeted biological agent which connect cytotoxic drug to monoclonal antibody by a connector head, which enables monoclonal antibody acted as a carrier to efficiently transport small molecular cytotoxic drugs to target tumor cells. It is very important for clinicians to have an in-depth understanding of the molecular characteristics and mechanism of ADC drugs, rationally choose the appropriate dose, course of treatment and manage adverse reactions according to the indications during the clinical application of ADC drugs, which may even affect the survival of patients. Therefore, the consensus aims to conduct a systematic overview of commercially available ADC drugs, provide effective recommendations and references for clinicians to better apply and manage ADC drugs.
Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Consensus ; Humans ; Immunoconjugates/therapeutic use* ; Neoplasms/drug therapy*

Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel. It is commonly used as an expectorant and supplementary anti-cancer drug. β-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose. Upon their interaction, β-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid, which inhibits cytochrome C oxidase, the terminal enzyme in the mitochondrial respiration chain, and suspends adenosine triphosphate synthesis, resulting in cell death. Hydrocyanic acid is a cell-cycle-stage-nonspecific agent that kills cancer cells. Thus, β-glucosidase can be coupled with a tumor-specific monoclonal antibody. β-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a killing effect. β-Glucosidase is injected intravenously and recognizes cancer-cell-surface antigens with the help of an antibody. The prodrug amarogentin is infused after β-glucosidase has reached the target position. Coupling of cell membrane peptides with β-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein. The Chinese medicine amarogentin and β-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed.
Amygdalin ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Cell-Penetrating Peptides ; therapeutic use ; Humans ; Iridoids ; therapeutic use ; Prodrugs ; therapeutic use ; beta-Glucosidase ; therapeutic use

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Humans ; Immunoconjugates/therapeutic use* ; Lung Neoplasms/drug therapy* ; Neoplasms/drug therapy*

Antineoplastic Agents ; therapeutic use ; Clinical Trials as Topic ; Humans

The prolongation of patient's overall survival is the accepted as gold standard to prove clinical values of anti-cancer drugs. However, if overall survival is taken as the primary endpoint in clinical trials for cancer types with a relatively good prognosis in the process of new anti-cancer drug research and development, the time to market the drugs will be prolonged due to the long follow-up time. In addition, overall survival is often interfered by confounding factors such as follow-up treatment. Therefore, regulatory agencies have established an accelerated review model using surrogate endpoints for the approval of new anti-cancer drugs, but there are still some problems in the use of surrogate endpoints in cancer clinical trials. From the perspective of new drug review, the authors expounds the key points of confirming and rationally using surrogate endpoints in clinical trials of anti-cancer drugs, which will improve the level of clinical trials of new anti-cancer drugs and accelerate the development of anti-tumor drugs.
Humans ; Neoplasms/therapy* ; Antineoplastic Agents/therapeutic use* ; Biomarkers

The antitumor drug has become one of the focused areas in new drug research and development. Their clinical research generally consumes a long period of time, with high cost and high risk. Model-informed drug development (MIDD) integrates and quantitatively analyzes physiological, pharmacological, and disease progression information through modeling and simulation, which can reduce the cost of drug development and improve the efficiency of clinical research. In this essay, Osimertinib and Pembrolizumab are given as examples to illustrate the specific application of MIDD in different phases of clinical research, aiming to provide references for the application of MIDD to guide the clinical research of antitumor drugs.
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Antineoplastic Agents/therapeutic use* ; Drug Development ; Humans ; Lung Neoplasms