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Japanese Journal of Clinical Oncology Mar 2020Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens... (Review)
Review
Systemic therapies for operable breast cancer patients have improved outcomes and have thus become standard treatments. Recently, new molecular target drugs and regimens are being developed based on the predicted sensitivity for specific breast cancer histological types. Systemic therapy is selected according to recurrence risk, with the treatment for low-risk patients being de-escalated, while high-risk patients receive aggressive systemic treatment with an adequate dose and duration. Neoadjuvant systemic therapy has a different aim. The efficacy of systemic therapies, based on the sensitivities to drugs, is supported by improvements in the rate of breast-conserving therapy. The response to neoadjuvant systemic therapy is the most important factor for predicting outcomes and selecting the optimal adjuvant therapy. Novel biological markers unique to individual patients allow appropriate targeted therapy, which can achieve optimal efficacy.
Topics: Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy
PubMed: 32147701
DOI: 10.1093/jjco/hyz213 -
Nature Reviews. Clinical Oncology Sep 2021The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the... (Review)
Review
The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the modality of definitive local treatment (surgery or radiotherapy) and the associated systemic therapies to further improve the likelihood of cure. Trial evidence supports cisplatin-based adjuvant therapy either after surgical resection or concurrently with radiotherapy. Consensus guidelines support neoadjuvant chemotherapy in lieu of adjuvant chemotherapy and carboplatin-based regimens for patients who are ineligible for cisplatin. The incorporation of newer agents, now standard for patients with stage IV lung cancer, into the curative therapy paradigm has lagged owing to inefficient trial designs, the lengthy follow-up needed to assess survival end points and a developmental focus on the advanced-stage disease setting. Surrogate end points, such as pathological response, are being studied and might shorten trial durations. In 2018, the anti-PD-L1 antibody durvalumab was approved for patients with stage III lung cancer after concurrent chemoradiotherapy. Since then, the study of targeted therapies and immunotherapies in patients with early-stage lung cancer has rapidly expanded. In this Review, we present the current considerations in the treatment of patients with early-stage lung cancer and explore the current and future state of clinical research to develop systemic therapies for non-metastatic lung cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Lung Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Therapies, Investigational
PubMed: 33911215
DOI: 10.1038/s41571-021-00501-4 -
Drug Design, Development and Therapy 2020Neoadjuvant chemotherapy is increasingly used in breast cancer, especially for downstaging the primary tumor in the breast and the metastatic axillary lymph node.... (Review)
Review
Neoadjuvant chemotherapy is increasingly used in breast cancer, especially for downstaging the primary tumor in the breast and the metastatic axillary lymph node. Accurate evaluations of the response to neoadjuvant chemotherapy provide important information on the impact of systemic therapies on breast cancer biology, prognosis, and guidance for further therapy. Moreover, pathologic complete response is a validated and valuable surrogate prognostic factor of survival after therapy. Evaluations of neoadjuvant chemotherapy response are very important in clinical work and basic research. In this review, we will elaborate on evaluations of the efficacy of neoadjuvant chemotherapy in breast cancer and provide a clinical evaluation procedure for neoadjuvant chemotherapy.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Neoadjuvant Therapy
PubMed: 32606609
DOI: 10.2147/DDDT.S253961 -
Frontiers in Immunology 2019Accumulating data on cellular and molecular pathways help to develop novel therapeutic strategies in skin inflammation and autoimmunity. Examples are psoriasis and... (Review)
Review
Accumulating data on cellular and molecular pathways help to develop novel therapeutic strategies in skin inflammation and autoimmunity. Examples are psoriasis and atopic dermatitis, two clinically and immunologically well-defined disorders. Here, the elucidation of key pathogenic factors such as IL-17A/IL-23 on the one hand and IL-4/IL-13 on the other hand profoundly changed our therapeutic practice. The knowledge on intracellular pathways and governing factors is shifting our attention to new druggable molecules. Multiple cytokine receptors signal through Janus kinases (JAKs) and associated signal transducer and activators of transcription (STATs). Inhibition of JAKs can simultaneously block the function of multiple cytokines. Therefore, JAK inhibitors (JAKi) are emerging as a new class of drugs, which in dermatology can either be used systemically as oral drugs or locally in topical formulations. Inhibition of JAKs has been shown to be effective in various skin disorders. The first oral JAKi have been recently approved for the treatment of rheumatoid arthritis and psoriatic arthritis. Currently, multiple inhibitors of the JAK/STAT pathway are being investigated for skin diseases like alopecia areata, atopic dermatitis, dermatomyositis, graft-versus-host-disease, hidradenitis suppurativa, lichen planus, lupus erythematosus, psoriasis, and vitiligo. Here, we aim to discuss the immunological basis and current stage of development of JAKi in dermatology.
Topics: Administration, Topical; Animals; Dermatology; Graft vs Host Disease; Humans; Janus Kinase Inhibitors; Skin Diseases
PubMed: 31849996
DOI: 10.3389/fimmu.2019.02847 -
Modern Pathology : An Official Journal... Jan 2018Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging... (Review)
Review
Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging immunotherapies. These approaches can be used alone or in combination depending on the clinical scenario. ADT is typically reserved for high-risk locally or systemically advanced disease that is not amenable to curative surgery. Radiation therapy can be used instead of surgery as primary therapy with curative intent for low-intermediate-risk disease as well as for control of locally advanced disease not suitable for surgery. Ablative therapies can be used as primary therapy for low-intermediate-risk disease or as salvage therapy for clinically localized disease where RT has failed. Chemotherapy and immune-based therapies are currently used for androgen-independent disease, although the indications for these approaches may well change as new data from clinical trials accrue. Pathologists should be able to recognize tissue changes associated with these treatments to provide information that will optimize patient management. This is particularly true in situations where clinical history of recent or remote nonsurgical treatment is not provided with the specimen. In the absence of this information, pathologists encountering the features described herein are encouraged to review patient records or communicate directly with clinical colleagues to determine how a given patient was treated and when.
Topics: Androgen Antagonists; Cryotherapy; Dietary Supplements; Drug Therapy; Extracorporeal Shockwave Therapy; Humans; Immunotherapy; Laser Therapy; Male; Neoplasm Grading; Photochemotherapy; Prostatic Neoplasms; Treatment Outcome
PubMed: 29297495
DOI: 10.1038/modpathol.2017.158 -
Clinical Cancer Research : An Official... Jun 2020While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional...
PURPOSE
While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known.
EXPERIMENTAL DESIGN
PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor.
RESULTS
Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24-0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10-0.31) and HER2 (HR = 0.32; 95% PI, 0.21-0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15-0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19-0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27-0.54), with no significant difference between the two groups ( = 0.60).
CONCLUSIONS
Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2 breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response..
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local
PubMed: 32046998
DOI: 10.1158/1078-0432.CCR-19-3492 -
Annals of Surgical Oncology Apr 2021While historically breast cancer has been treated with primary surgery followed by adjuvant therapy, the delivery of systemic therapy in the neoadjuvant setting has... (Review)
Review
While historically breast cancer has been treated with primary surgery followed by adjuvant therapy, the delivery of systemic therapy in the neoadjuvant setting has become increasingly common, especially for triple-negative and HER2-positive breast cancer. The initial motivations for pursuing neoadjuvant chemotherapy (NAC) were decreasing the tumor burden in the breast and axilla to enable de-escalation of surgery, and use the strategy to advance drug development. While these remain of interest, recent trials have additionally demonstrated survival advantages from escalation of systemic treatment in patients with residual disease, and new studies are testing de-escalation of systemic therapy based on pathologic response. Thus, response information to NAC has become pivotal to guide adjuvant treatment recommendations, and has resulted in NAC being the preferred approach for most HER2-positive and triple-negative breast cancers. Herein, we review select landmark trials that have paved the way for the use of chemotherapy in the neoadjuvant setting for breast cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Axilla; Breast Neoplasms; Chemotherapy, Adjuvant; Humans; Neoadjuvant Therapy; Neoplasm, Residual; Receptor, ErbB-2; Treatment Outcome; Triple Negative Breast Neoplasms
PubMed: 33486641
DOI: 10.1245/s10434-020-09480-9 -
Drug Delivery Dec 2022Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g.... (Review)
Review
Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.
Topics: Administration, Oral; Alginates; Chitosan; Colitis, Ulcerative; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Pharmaceutical Preparations
PubMed: 35384787
DOI: 10.1080/10717544.2022.2058646 -
Clinical Microbiology and Infection :... Nov 2019Adjunctive systemic antibiotic therapy for treatment of bacterial endophthalmitis is controversial but common practice due to the severity of the disease. In the absence... (Review)
Review
BACKGROUND
Adjunctive systemic antibiotic therapy for treatment of bacterial endophthalmitis is controversial but common practice due to the severity of the disease. In the absence of guidance documents, several antibiotic regimens are being used without applying evidence-based prescribing, leading to inappropriate treatment of this serious eye condition.
OBJECTIVES
To summarize available data on intravitreal penetration of systemically administered antibiotics and to discuss their usefulness from a microbiological and pharmacological point of view.
SOURCES
We performed a systematic PubMed search of studies investigating antibiotic concentrations in the vitreous after systemic administration in humans, and selected animal models.
CONTENT
The best-documented agents achieving therapeutic levels in the vitreous are meropenem, linezolid and moxifloxacin. Vancomycin, cefazoline, ceftriaxone, ceftazidime, imipenem and trimethoprim-sulfamethoxazole reach levels justifying their use in specific situations. Available data do not support the use of ciprofloxacin, levofloxacin, aminoglycosides, aminopenicillins, piperacillin, cefepime and clarithromycin. With very limited but available promising data, the use of daptomycin and rifampicin deserves further investigation.
IMPLICATIONS
The choice of the adjunctive systemic antibiotic agent-in situations where it is considered relevant for treatment-must to date be made on an individual basis, considering microbiological aspects as well as operative status and inflammation of the eye. This review gives a systematic overview of antibiotic options and provides guidance to the clinician striving for optimal systemic antibiotic treatment of bacterial endophthalmitis.
Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Bacterial Infections; Disease Models, Animal; Endophthalmitis; Humans; Vitreous Body
PubMed: 30771529
DOI: 10.1016/j.cmi.2019.01.017 -
Journal of Clinical Pharmacology May 2016Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many... (Review)
Review
Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many anterior segment diseases are treated pharmacologically through eye drops, which have an implied therapeutic index of local therapy. Unlike oral dosage forms administered for systemic diseases, eyedrops require patients not only to adhere to treatment, but to be able to accurately perform-ie, instill drops correctly. Anatomical and physiological barriers make topical delivery to the anterior chamber challenging-in some cases more challenging than absorption through the skin, nasal passages, or gut. Treatment of the posterior segment (eg, vitreous, retina, choroid, and optic nerve) is more challenging due to additional barriers. Recently, intravitreal injections have become a standard of care with biologics for the treatment of macular degeneration and other diseases. Although the eye has esterases, hydroxylases, and transporters, it has relatively little CYP450 enzymes. Because it is challenging to obtain drug concentrations at the target site, ocular clinical pharmacokinetics, and thus pharmacokinetic-pharmacodynamic interactions, are rarely available. Ophthalmic pharmaceuticals require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Although applied locally, ocular medications may be absorbed systemically, which results in morbidity and mortality (eg, systemic hypotension, bronchospasm, and bradycardia).
Topics: Animals; Drug Delivery Systems; Eye Diseases; Humans
PubMed: 26360129
DOI: 10.1002/jcph.634