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Journal of Cancer Research and... 2016Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular... (Meta-Analysis)
Meta-Analysis Review
Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular deoxyribonucleic acid (DNA) by leading covalent bifunctional DNA adducts with cellular DNA. Major side effects of oxaliplatin are neurotoxicity (peripheral neuropathy), myelosuppression with moderate thrombocytopenia and gastrointestinal toxicity (diarrhea). Thrombocytopenia might be related to myelosuppression and/or drug-induced immune thrombocytopenia (DIIT). In here, oxaliplatin-induced thrombocytopenia is discussed with review of the literature.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Gastrointestinal Neoplasms; Humans; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia
PubMed: 27461601
DOI: 10.4103/0973-1482.154056 -
Basic & Clinical Pharmacology &... Sep 2018The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably.... (Randomized Controlled Trial)
Randomized Controlled Trial
The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably. In this study, we investigated the previously reported SNPs 1199G>A (rs2229109), 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) in ABCB1, and 1196A>G (rs10509681) in CYP2C8 and their association with treatment-induced myelosuppression, progression-free survival (PFS) and overall survival (OS). From the phase III study, OAS-07OVA, 525 patients (All) treated with carboplatin and paclitaxel administered as Paclical (Arm A, n = 260) or Taxol (Arm B, n = 265) were included and genotyped using pyrosequencing. Genotype associations with myelosuppression, PFS and OS were investigated using anova, Kaplan-Meier analysis and Cox proportional hazard models. The most prominent finding was for the ABCB1 variant 3435TT, which was significantly associated with increased PFS in All (hazard ratio (HR) = 0.623), in Arm A (HR = 0.590) and in Arm B (HR = 0.627), as well as increased OS in All (HR = 0.443) and in Arm A (HR = 0.372) compared to the wild-type, 3435CC. For toxicity, the most interesting finding concerned the haplotype, including 1236TT, 2677TT and 3435TT, which was associated with higher neutrophil values in Arm B (p = 0.039) and less neutrophil decrease in All (p = 0.048) and in Arm B (p = 0.021). It is noteworthy that the results varied depending on the treatment arm which indicates that the effects of ABCB1 variants vary with the treatment regimen. Our results reflect the contradictory results of previous studies, confirming that small variations in the composition of treatment regimens and patient populations may influence the interpretation of SNPs effects on treatment outcome.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Female; Genotype; Humans; Kaplan-Meier Estimate; Middle Aged; Neutrophils; Ovarian Neoplasms; Paclitaxel; Polymorphism, Single Nucleotide; Proportional Hazards Models; Survival Rate; Treatment Outcome
PubMed: 29504705
DOI: 10.1111/bcpt.12997 -
Internal and Emergency Medicine Oct 2022Colchicine is a tricyclic, lipid-soluble alkaloid which has long been used to treat gout and many immunological diseases. Due to its narrow therapeutic window and long... (Review)
Review
Colchicine is a tricyclic, lipid-soluble alkaloid which has long been used to treat gout and many immunological diseases. Due to its narrow therapeutic window and long half-life of elimination, colchicine overdose occurs occasionally. Unfortunately, some patients lost their lives because of colchicine overdose or suicide. Acute colchicine poisoning can lead to original gastrointestinal disorders, shock, progressive multiple organ failure, and myelosuppression. Although many researchers in the world performed lots of research, there are currently no specific antidotes for colchicine poisoning. Meanwhile, there are no management guidelines to treat patients with acute colchicine poisoning until now. Herein, we systematically elaborate on the clinical features and progress in the management of acute colchicine poisoning in adults according to the previous literature. This paper will provide some valuable and available information for clinicians.
Topics: Adult; Antidotes; Colchicine; Humans; Lipids; Multiple Organ Failure; Poisoning; Suicide
PubMed: 36028733
DOI: 10.1007/s11739-022-03079-6 -
Frontiers in Pharmacology 2023This study aims to assess the clinical efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression in adult patients through meta-analysis....
This study aims to assess the clinical efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression in adult patients through meta-analysis. The PubMed, Embase, Cochrane Library, Clinical Trials, EU Clinical Trials Register, and International Clinical Trials Registry Platform were searched up to 25 October 2022. Only randomized controlled trials (RCTs) comparing the clinical outcomes of Trilaciclib and Trilaciclib plus chemotherapy for treating malignant cancers in adult patients were included. The primary outcome included the incidence of SN, FN, the DSN, and administration of ESAs, G-CSFs, and RBC or platelet transfusions, while the secondary outcomes included the risk of adverse events (AEs) and severe adverse events (SAEs). In total, four randomized controlled trials (RCTs) involving 345 patients with SCLC or breast cancer were included in this meta-analysis. Results showed that administration of Trilaciclib significantly reduced the occurrence of SN (19.3% vs. 42.2%, OR = 0.31), FN (3.22% vs. 6.72%, OR = 0.47), anemia (20.5% vs. 38.2%, OR = 0.38) and shortened the DSN during treatment. The proportion of patients receiving therapeutic use of ESAs (4.03% vs. 11.8%, OR = 0.31), G-CSF (37.0% vs. 53.5%, OR = 0.52), RBC transfusions (19.8% vs. 29.9%, OR = 0.56) was also statistically lower in the experimental group than in the control group. Meanwhile, the ORR, overall survival, and progress-free survival of the two groups were identical, and no negative impact of Trilaciclib on the clinical outcomes of chemotherapy treatments was found. Other chemotherapy-induced adverse events (AEs) and severe adverse events (SAEs) like diarrhea, fatigue, nausea, and vomiting were identical regardless of Trilaciclib usage. Trilaciclib demonstrated its efficacy in reducing the occurrence of chemotherapy-induced myelosuppression and utilization of supportive care interventions without undermining the clinical benefits of chemotherapy regimens during treatment with an acceptable safety profile.
PubMed: 37305548
DOI: 10.3389/fphar.2023.1157251 -
Paediatrics and Child Health Mar 2020Febrile neutropenia (FN) is a common and dangerous consequence of myelosuppressive chemotherapy but can occur as part of the disease processes. Bacterial bloodstream... (Review)
Review
Febrile neutropenia (FN) is a common and dangerous consequence of myelosuppressive chemotherapy but can occur as part of the disease processes. Bacterial bloodstream infection is the most commonly diagnosed cause of febrile neutropenia, with Gram-positive organisms most frequently isolated. However, Gram-negative organisms are becoming more prevalent, with a worrying trend towards resistant organisms. When FN is prolonged, lasting for more than 5 days, there is an increased risk of invasive fungal infections. Prompt recognition, diagnosis and initiation of treatment with broad-spectrum antibiotics are essential to avoid complications and prevent rapid progression to sepsis and possible death. This short article summarises the definition, causes, pathogenesis, applied physiology and management of FN in children.
PubMed: 32336983
DOI: 10.1016/j.paed.2019.12.002 -
Nutrients Aug 2022Myelosuppression is a common and intractable side effect of cancer therapies including radiotherapy and chemotherapy, while the underlying mechanism remains incompletely...
Myelosuppression is a common and intractable side effect of cancer therapies including radiotherapy and chemotherapy, while the underlying mechanism remains incompletely understood. Here, using a mouse model of radiotherapy-induced myelosuppression, we show that inorganic phosphate (Pi) metabolism is acutely inhibited in hematopoietic stem cells (HSCs) during irradiation-induced myelosuppression, and closely correlated with the severity and prognosis of myelosuppression. Mechanistically, the acute Pi metabolic inhibition in HSCs results from extrinsic Pi loss in the bone marrow niche and the intrinsic transcriptional suppression of soluble carrier family 20 member 1 (SLC20A1)-mediated Pi uptake by p53. Meanwhile, Pi metabolic inhibition blunts irradiation-induced Akt hyperactivation in HSCs, thereby weakening its ability to counteract p53-mediated Pi metabolic inhibition and the apoptosis of HSCs and consequently contributing to myelosuppression progression. Conversely, the modulation of the Pi metabolism in HSCs via a high Pi diet or renal Klotho deficiency protects against irradiation-induced myelosuppression. These findings reveal that Pi metabolism and HSC survival are causally linked by the Akt/p53-SLC20A1 axis during myelosuppression and provide valuable insights into the pathogenesis and management of myelosuppression.
Topics: Bone Marrow; Hematopoietic Stem Cells; Phosphates; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53
PubMed: 36014901
DOI: 10.3390/nu14163395 -
Patient Preference and Adherence 2021To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to...
PURPOSE
To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the "patient voice" describing how CIM impacts their daily lives.
PARTICIPANTS AND METHODS
Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: "In your own words, please describe how side effects from myelosuppression have impacted your life."
RESULTS
Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1-10 scale of "bothersomeness"). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24-43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family.
CONCLUSION
Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.
PubMed: 33658769
DOI: 10.2147/PPA.S292462