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Journal of Neurology Sep 2021Oxaliplatin (OXA) is a commonly used platinum-based chemotherapy drug for colorectal cancer. OXA-induced peripheral neurotoxcity (OIPN) is a comprehensive adverse... (Review)
Review
Oxaliplatin (OXA) is a commonly used platinum-based chemotherapy drug for colorectal cancer. OXA-induced peripheral neurotoxcity (OIPN) is a comprehensive adverse reaction of OXA. OIPN can be divided into acute and chronic types according to clinical features and different mechanisms. The main clinical features of acute OIPN are cold-sensitive sensory symptoms and neuropathic pain in limbs. In addition to the above symptoms, chronic OIPN also produces autonomic nerve dysfunction. The most important mechanism involved in acute OIPN is the alteration of voltage-gated Na + channels, and nuclear DNA damage in chronic OIPN. There are some methods like reducing exposure to cold, calcium and magnesium salts, amifostine could be beneficial in acute OIPN prevention and dose modification, changing in schedule glutathione, duloxetine, selective serotonin reuptake inhibitors, carbonic anhydrase inhibitor in chronic OIPN prevention. Recent updates are provided in this article in relation to the clinical features, potential mechanisms, prevention and treatment of OIPN.
Topics: Antineoplastic Agents; Humans; Oxaliplatin; Peripheral Nervous System Diseases
PubMed: 32474658
DOI: 10.1007/s00415-020-09942-w -
Current Neuropharmacology 2019Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory... (Review)
Review
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory abnormities are common and the most suffering issues. The pathogenesis of CIPN has not been completely understood, and strategies for CIPN prevention and treatment are still open problems for medicine.
OBJECTIVES
The objective of this paper is to review the mechanism-based therapies against sensory abnormities in CIPN.
METHODS
This is a literature review to describe the uncovered mechanisms underlying CIPN and to provide a summary of mechanism-based therapies for CIPN based on the evidence from both animal and clinical studies.
RESULTS
An abundance of compounds has been developed to prevent or treat CIPN by blocking ion channels, targeting inflammatory cytokines and combating oxidative stress. Agents such as glutathione, mangafodipir and duloxetine are expected to be effective for CIPN intervention, while Ca/Mg infusion and venlafaxine, tricyclic antidepressants, and gabapentin display limited efficacy for preventing and alleviating CIPN. And the utilization of erythropoietin, menthol and amifostine needs to be cautious regarding to their side effects.
CONCLUSIONS
Multiple drugs have been used and studied for decades, their effect against CIPN are still controversial according to different antineoplastic agents due to the diverse manifestations among different antineoplastic agents and complex drug-drug interactions. In addition, novel therapies or drugs that have proven to be effective in animals require further investigation, and it will take time to confirm their efficacy and safety.
Topics: Animals; Antineoplastic Agents; Drug Therapy, Combination; Humans; Inflammation; Neuroprotective Agents; Peripheral Nervous System Diseases; Treatment Outcome
PubMed: 28925884
DOI: 10.2174/1570159X15666170915143217 -
The Lancet. Child & Adolescent Health Feb 2020Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse... (Review)
Review
Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.
Topics: Adolescent; Antineoplastic Agents; Child; Cisplatin; Female; Hearing Loss; Humans; Male; Neoplasms; Ototoxicity; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Thiosulfates
PubMed: 31866182
DOI: 10.1016/S2352-4642(19)30336-0 -
Science Immunology Jun 2022Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal...
Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited significantly elevated postirradiation CD47 levels. The combination of RT, anti-SIRPα, and anti-PD-1 reversed adaptive immune resistance and drove efficient TAA cross-presentation, resulting in robust TAA-specific CD8 T cell priming, functional activation of T effectors, and increased T cell clonality and clonal diversity. We observed significantly higher complete response rates to RT/anti-SIRPα/anti-PD-1 in both irradiated and abscopal tumors and prolonged survival in three distinct murine CRC models, including a cecal orthotopic model. The efficacy of triple combination therapy was STING dependent as knockout animals lost most benefit of adding anti-SIRPα and anti-PD-1 to RT. Despite activation across the myeloid stroma, the enhanced dendritic cell function accounts for most improvements in CD8 T cell priming. These data suggest ATR-mediated CD47 and PD-L1 up-regulation as a key mechanism restraining radiation-induced immune priming. RT combined with SIRPα and PD-1 blockade promotes robust antitumor immune priming, leading to systemic tumor regressions.
Topics: Animals; Antigens, Neoplasm; Ataxia Telangiectasia Mutated Proteins; B7-H1 Antigen; CD47 Antigen; Colorectal Neoplasms; Humans; Mice; Programmed Cell Death 1 Receptor; Up-Regulation
PubMed: 35687697
DOI: 10.1126/sciimmunol.abl9330 -
Nature Communications Mar 2022Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need....
Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.
Topics: Gastrointestinal Microbiome; Homeostasis; Humans; Intestines; Microalgae; Neoplasms; Radiation-Protective Agents
PubMed: 35301299
DOI: 10.1038/s41467-022-28744-4 -
Patient Preference and Adherence 2015Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC... (Review)
Review
BACKGROUND
Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.
METHODS
A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.
RESULTS
"SC better than IV" involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. "IV better than SC" involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. "IM better than IV" involves epinephrine, hepatitis B immu-noglobulin, pegaspargase, and some antibiotics. "IV better than IM" involves ketamine, morphine, and antivenom. "IM better than SC" involves epinephrine. "SC better than IM" involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and pharmacoeconomics because patient preference will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction, while pharmacoeconomic concern will help alleviate nurse shortages and reduce overall health care costs. Besides the principles, the following detailed factors might affect the decision: patient characteristics-related factors (body mass index, age, sex, medical status [eg, renal impairment, comorbidities], personal attitudes toward safety and convenience, past experience, perception of current disease status, health literacy, and socioeconomic status), medication administration-related factors (anatomical site of injection, dose, frequency, formulation characteristics, administration time, indication, flexibility in the route of administration), and health care staff/institution-related factors (knowledge, human resources).
CONCLUSION
This updated review of findings of comparative studies of different injection routes will enrich the knowledge of safe, efficacious, economic, and patient preference-oriented medication administration as well as catching research opportunities in clinical nursing practice.
PubMed: 26170642
DOI: 10.2147/PPA.S87271 -
Blood Reviews Mar 2024Melphalan, has been a major component of myeloma therapy since the 1950s. In the context of hematopoietic cell transplantation (HCT), high dose melphalan (HDM) is the... (Review)
Review
Melphalan, has been a major component of myeloma therapy since the 1950s. In the context of hematopoietic cell transplantation (HCT), high dose melphalan (HDM) is the most common conditioning regimen used due to its potent anti-myeloma effects and manageable toxicities. Common toxicities associated with HDM include myelosuppression, gastrointestinal issues, and mucositis. Established approaches to reduce these toxicities encompass dose modification, nausea prophylaxis with 5HT3 receptor antagonists, cryotherapy, amifostine use, and growth factors. Optimization of melphalan exposure through personalized dosing and its combination with other agents like busulfan, or bendamustine show promise. Propylene glycol-free melphalan (Evomela) represents a novel formulation aiming to enhance drug stability and reduce adverse effects. This review explores strategies to enhance the efficacy and mitigate the toxicity of HDM in multiple myeloma. Future directions involve exploring these strategies in clinical trials to improve the safety and efficacy of HDM, thereby enhancing outcomes for multiple myeloma patients undergoing autologous HCT.
Topics: Humans; Melphalan; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Busulfan; Bendamustine Hydrochloride; Transplantation, Autologous; Transplantation Conditioning
PubMed: 38097487
DOI: 10.1016/j.blre.2023.101162 -
Therapeutic Advances in Medical Oncology 2020Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major... (Review)
Review
Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m) are needed.
PubMed: 32489432
DOI: 10.1177/1758835920923430 -
Molecular Pharmaceutics Nov 2023Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by... (Review)
Review
Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.
Topics: Humans; Amifostine; Radiation Protection; Radiation-Protective Agents; Administration, Intravenous; Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37747899
DOI: 10.1021/acs.molpharmaceut.3c00600