A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma
| Autor: | Andrew Hodgkiss, Daisy Mak, Rajesh Kumar, Mary O'Brien, Jaishree Bhosle, R. Gunapala, D. Walder, Sanjay Popat, Anna Minchom, Nadia Yousaf |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Mesothelioma B Vitamins Lung Neoplasms Homocysteine Cancer Treatment Toxicology Pathology and Laboratory Medicine Gastroenterology chemistry.chemical_compound 0302 clinical medicine Carcinoma Non-Small-Cell Lung Medicine and Health Sciences Clinical endpoint Medicine Prospective Studies Prospective cohort study Aged 80 and over education.field_of_study Multidisciplinary Depression Organic Compounds Pharmaceutics Vitamins Middle Aged Vitamin B 12 Chemistry Treatment Outcome Pemetrexed Oncology 030220 oncology & carcinogenesis Physical Sciences Toxicity Female Research Article medicine.drug Adult Vitamin medicine.medical_specialty General Science & Technology Science Population Cobalamins 03 medical and health sciences Folic Acid Drug Therapy Internal medicine Mental Health and Psychiatry Humans Chemotherapy Vitamin B12 education Aged Mood Disorders business.industry Mesothelioma Malignant Organic Chemistry Chemical Compounds Biology and Life Sciences 030228 respiratory system chemistry Dietary Supplements business Biomarkers |
| Zdroj: | PLoS ONE, Vol 14, Iss 11, p e0225509 (2019) PLoS ONE |
| Popis: | ObjectivesVitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity.Material and methodsPrimary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities.ResultsEighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (ConclusionOn-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short. |
| Databáze: | OpenAIRE |
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