-
The International Journal of... Dec 2014We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease.
METHODS
We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects.
RESULTS
Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects.
CONCLUSIONS
Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Cholinesterase Inhibitors; Cognition; Combined Modality Therapy; Female; Humans; Male; Memantine; Treatment Outcome
PubMed: 25548104
DOI: 10.1093/ijnp/pyu115 -
Acta Pharmacologica Sinica Feb 2023As a breakthrough strategy for cancer treatment, immunotherapy mainly consists of immune checkpoint inhibitors (ICIs) and other immunomodulatory drugs that provide a... (Review)
Review
As a breakthrough strategy for cancer treatment, immunotherapy mainly consists of immune checkpoint inhibitors (ICIs) and other immunomodulatory drugs that provide a durable protective antitumor response by stimulating the immune system to fight cancer. However, due to the low response rate and unique toxicity profiles of immunotherapy, the strategies of combining immunotherapy with other therapies have attracted enormous attention. These combinations are designed to exert potent antitumor effects by regulating different processes in the cancer-immunity cycle. To date, immune-based combination therapy has achieved encouraging results in numerous clinical trials and has received Food and Drug Administration (FDA) approval for certain cancers with more studies underway. This review summarizes the emerging strategies of immune-based combination therapy, including combinations with another immunotherapeutic strategy, radiotherapy, chemotherapy, anti-angiogenic therapy, targeted therapy, bacterial therapy, and stroma-targeted therapy. Here, we highlight the rationale of immune-based combination therapy, the biomarkers and the clinical progress for these immune-based combination therapies.
Topics: Humans; Neoplasms; Combined Modality Therapy; Immunotherapy
PubMed: 35927312
DOI: 10.1038/s41401-022-00953-z -
Journal For Immunotherapy of Cancer Jun 2018Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing... (Review)
Review
Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.
Topics: Animals; Combined Modality Therapy; Disease Models, Animal; Humans; Mice; Neoplasms; Programmed Cell Death 1 Receptor; Radiotherapy
PubMed: 29866197
DOI: 10.1186/s40425-018-0361-7 -
Ophthalmologica. Journal International... 2013This paper aims to describe the current situation of choroidal neovascularization (CNV) treatment. (Review)
Review
PURPOSE
This paper aims to describe the current situation of choroidal neovascularization (CNV) treatment.
PROCEDURES
MEDLINE (2001-2013) was searched for original research studies (phase I, II, III), abstracts and review articles concerning CNV therapy, and other related articles. Selected information from related websites was also included.
RESULTS
The management of CNV was developed through laser photocoagulation and photodynamic therapy, and has now evolved into anti-vascular endothelial growth factor (VEGF) use. Patients have achieved better visual acuity and toleration with the development of this therapy strategy. Combination therapy appears to offer a reduced retreatment frequency and long-term maintenance of the benefit with appropriate combination. Other treatment explorations with anti-inflammation and anti-VEGF are also ongoing.
CONCLUSIONS
Anti-VEGF monotherapy has become the first treatment for CNV patients. The investigation of other therapy strategies may prolong the interval of treatment and provide alternatives to CNV treatment.
Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Combined Modality Therapy; Humans; Laser Coagulation; Photochemotherapy; Vascular Endothelial Growth Factor A
PubMed: 23949022
DOI: 10.1159/000351660 -
Frontiers in Immunology 2023Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and... (Review)
Review
Colorectal cancer (CRC) is a deadly form of cancer worldwide. Patients with locally advanced rectal cancer and metastatic CRC have a poor long-term prognosis, and rational and effective treatment remains a major challenge. Common treatments include multi-modal combinations of surgery, radiotherapy, and chemotherapy; however, recurrence and metastasis rates remain high. The combination of radiotherapy and immunotherapy (radioimmunotherapy [RIT]) may offer new solutions to this problem, but its prospects remain uncertain. This review aimed to summarize the current applications of radiotherapy and immunotherapy, elaborate on the underlying mechanisms, and systematically review the preliminary results of RIT-related clinical trials for CRC. Studies have identified several key predictors of RIT efficacy. Summarily, rational RIT regimens can improve the outcomes of some patients with CRC, but current study designs have limitations. Further studies on RIT should focus on including larger sample sizes and optimizing the combination therapy regimen based on underlying influencing factors.
Topics: Humans; Radioimmunotherapy; Combined Modality Therapy; Immunotherapy; Treatment Outcome; Colorectal Neoplasms
PubMed: 37234164
DOI: 10.3389/fimmu.2023.1105180 -
Molecules (Basel, Switzerland) Nov 2023Triple-negative breast cancer (TNBC) is one of the most heterogeneous and aggressive breast cancer subtypes with a high risk of death on recurrence. To date, TNBC is... (Review)
Review
Triple-negative breast cancer (TNBC) is one of the most heterogeneous and aggressive breast cancer subtypes with a high risk of death on recurrence. To date, TNBC is very difficult to treat due to the lack of an effective targeted therapy. However, recent advances in the molecular characterization of TNBC are encouraging the development of novel drugs and therapeutic combinations for its therapeutic management. In the present review, we will provide an overview of the currently available standard therapies and new emerging therapeutic strategies against TNBC, highlighting the promises that newly developed small molecules, repositioned drugs, and combination therapies have of improving treatment efficacy against these tumors.
Topics: Humans; Triple Negative Breast Neoplasms; Combined Modality Therapy; Drug Discovery
PubMed: 38005235
DOI: 10.3390/molecules28227513 -
Asian Journal of Andrology 2019Recent advances in genomics technology have led to the massive discovery of new drug targets for prostate cancer; however, none of the currently available therapeutics... (Review)
Review
Recent advances in genomics technology have led to the massive discovery of new drug targets for prostate cancer; however, none of the currently available therapeutics is curative. One of the greatest challenges is drug resistance. Combinations of therapies with distinct mechanisms of action represent a promising strategy that has received renewed attention in recent years. Combination therapies exert cancer killing functions through either concomitant targeting of multiple pro-cancer factors or more effective inhibition of a single pathway. Theoretically, the combination therapy can improve efficacy and efficiency compared with monotherapy. Although increasing numbers of drug combinations are currently being tested in clinical trials, the mechanisms by which these combinations can overcome drug resistance have yet to be fully understood. The purpose of this review is to summarize recent work on therapeutic combinations in the treatment of castration-resistant prostate cancer and discuss emerging mechanisms underlying drug resistance. In addition, we provide an overview of the current preclinical mechanistic studies on potential therapeutic combinations to overcome drug resistance.
Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Male; Prostatic Neoplasms, Castration-Resistant
PubMed: 30924449
DOI: 10.4103/aja.aja_10_19 -
International Journal of Clinical... May 2020Significant technological advances in radiotherapy have been made in the past few decades. High-precision radiotherapy has recently become popular and is contributing to... (Review)
Review
Significant technological advances in radiotherapy have been made in the past few decades. High-precision radiotherapy has recently become popular and is contributing to improvements in the local control of the irradiated target lesions and the reduction of adverse effects. Accordingly, for long-term survival, the importance of systemic cancer control, including at non-irradiated sites, is growing. Toward this challenge, the treatment methods in which anti-PD-1/PD-L1 antibodies that exert systemic effects by restoring anti-tumour immunity are combined with radiotherapy has attracted attention in recent years. Previous studies have reported the activation of anti-tumour immunity by radiotherapy, which simultaneously elevates PD-L1 expression, suggesting a potential for combination therapy. Radiotherapy induces so-called 'immunogenic cell death', which involves cell surface translocation of calreticulin and extracellular release of high-mobility group protein box 1 (HMGB-1) and adenosine-5'-triphosphate (ATP). Furthermore, radiotherapy causes immune activation via MHC class I upregulation and cGAS-STING pathway. In contrast, induction of immunosuppressive lymphocytes and the release of immunosuppressive cytokines and chemokines by radiotherapy contribute to immunosuppressive reactions. In this article, we review immune responses induced by radiotherapy as well as previous reports to support the rationale of combination of radiotherapy and anti-PD-1/PD-L1 antibodies. A number of preclinical and clinical studies have shown the efficacy of radiotherapy combined with immune checkpoint inhibition, hence combination therapy is considered to be an important future strategy for cancer treatment.
Topics: Animals; Antibodies; B7-H1 Antigen; Combined Modality Therapy; Humans; Immunosuppression Therapy; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Translational Research, Biomedical; Treatment Outcome
PubMed: 32246277
DOI: 10.1007/s10147-020-01666-1 -
Seminars in Radiation Oncology Jan 2015Radiation therapy (RT) is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell... (Review)
Review
Radiation therapy (RT) is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell killing, mounting evidence suggests that radiation can alter the tumor to become an immunostimulatory milieu. Data suggest that the immunogenic effects of radiation can be exploited to promote synergistic antitumor effects in combination with immunotherapeutic agents. We review concepts associated with the immunogenic consequences of RT and highlight how preclinical findings are translating into clinical benefit for patients receiving combination regimens of RT and therapeutic cancer vaccines.
Topics: Animals; Cancer Vaccines; Combined Modality Therapy; Humans; Mice; Neoplasms
PubMed: 25481266
DOI: 10.1016/j.semradonc.2014.07.002 -
Seminars in Oncology Aug 2015There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy,... (Review)
Review
There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy, and immunotherapy. Despite these advances, treatments such as monotherapy or monomodality have significant limitations. There is increasing interest in using these strategies in combination; however, it is not completely clear how best to incorporate molecularly targeted and immune-targeted therapies into combination regimens. This is particularly pertinent when considering combinations with immunotherapy, as other types of therapy may have significant impact on host immunity, the tumor microenvironment, or both. Thus, the influence of chemotherapy, radiation therapy, and molecularly targeted therapy on the host anti-tumor immune response and the host anti-host response (ie, autoimmune toxicity) must be taken into consideration when designing immunotherapy-based combination regimens. We present data related to many of these combination approaches in the context of investigations in patients with melanoma and discuss their potential relationship to management of patients with other tumor types. Importantly, we also highlight challenges of these approaches and emphasize the need for continued translational research.
Topics: Combined Modality Therapy; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Tumor Microenvironment
PubMed: 26320064
DOI: 10.1053/j.seminoncol.2015.05.007