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
Autoři:
Anna Minchom aff001; Daisy Mak aff001; Ranga Gunapala aff001; David Walder aff001; Rajiv Kumar aff001; Nadia Yousaf aff002; Andrew Hodgkiss aff003; Jaishree Bhosle aff001; Sanjay Popat aff002; Mary E. R. O’Brien aff001
Působiště autorů:
Lung Cancer Unit, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
aff001; Lung Cancer Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom
aff002; Adult Psychological Support Service, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
aff003
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225509
Souhrn
Objectives
Vitamin 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 methods
Primary 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.
Results
Eighty-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 (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3–4 toxicities.
Conclusion
On-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.
Klíčová slova:
Cancer treatment – Cobalamins – Depression – Drug therapy – Folic acid – Chemotherapy – Toxicity – Vitamins
Zdroje
1. Hanauske AR, Chen V, Paoletti P, et al. Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist 2001;6(4):363–73. [published Online First: 2001/08/29] doi: 10.1634/theoncologist.6-4-363 11524555
2. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21(14):2636–44. doi: 10.1200/JCO.2003.11.136 [published Online First: 2003/07/16] 12860938
3. Clarke R. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. Bmj 1998;316(7135):894–8. [published Online First: 1998/05/07] 9569395
4. Tanaka H, Horiike A, Sakatani T, et al. Plasma homocysteine levels and hematological toxicity in NSCLC patients after the first cycle of pemetrexed under folate supplementation. Anti-cancer drugs 2015;26(5):573–8. doi: 10.1097/CAD.0000000000000220 [published Online First: 2015/02/26] 25714250
5. Minchom AR, Saksornchai K, Bhosle J, et al. An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity. BMJ Open Respir Res 2014;1(1):e000061. doi: 10.1136/bmjresp-2014-000061 25553247
6. Eikelboom JW, Lonn E, Genest J Jr., et al. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Annals of internal medicine 1999;131(5):363–75. doi: 10.7326/0003-4819-131-5-199909070-00008 [published Online First: 1999/09/04] 10475890
7. Clarke R, Collins R. Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk? Design of clinical trials to test the homocysteine hypothesis of vascular disease. Journal of cardiovascular risk 1998;5(4):249–55. [published Online First: 1999/01/27] 9919473
8. Bostom AG, Rosenberg IH, Silbershatz H, et al. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham Study. Annals of internal medicine 1999;131(5):352–5. doi: 10.7326/0003-4819-131-5-199909070-00006 [published Online First: 1999/09/04] 10475888
9. Niyikiza C, Baker SD, Seitz DE, et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Molecular cancer therapeutics 2002;1(7):545–52. [published Online First: 2002/12/14] 12479273
10. Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000;69(2):228–32. [published Online First: 2000/07/15] doi: 10.1136/jnnp.69.2.228 10896698
11. Morabito A, Gebbia V, Di Maio M, et al. Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer 2013;81(1):77–83. doi: 10.1016/j.lungcan.2013.04.008 [published Online First: 2013/05/07] 23643177
12. Singh N, Baldi M, Kaur J, et al. MA 03.02 Timing of B12/Folate Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy: Final Results of the PEMVITASTART Randomized Trial. Journal of Thoracic Oncology 2017;12(11):S1807. doi: 10.1016/j.jtho.2017.09.461
13. Takagi Y, Hosomi Y, Sunami K, et al. A prospective study of shortened vitamin supplementation prior to cisplatin-pemetrexed therapy for non-small cell lung cancer. Oncologist 2014;19(11):1194–9. doi: 10.1634/theoncologist.2014-0221 [published Online First: 2014/09/28] 25260366
14. Schlei Z, Tan W, Faber MG, et al. Safety of Same-Day Vitamin B12 Supplementation in Patients Receiving Pemetrexed for the Treatment of Non-Small-Cell Lung Cancer or Pleural Mesothelioma: A Retrospective Analysis. Clin Lung Cancer 2018;19(6):467–75. doi: 10.1016/j.cllc.2018.05.017 [published Online First: 2018/10/30] 30369425
Článek vyšel v časopise
PLOS One
2019 Číslo 11
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy