Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-05-01T01:34:32.263Z Has data issue: false hasContentIssue false
  • English
  • Français

Chemotherapeutic drugs that penetrate the blood–brain barrier affect the development of hyperactive delirium in cancer patients

Published online by Cambridge University Press:  26 June 2014

Hiromichi Matsuoka ,
Kazuhiro Yoshiuchi ,
Atsuko Koyama ,
Masatomo Otsuka  and
Kazuhiko Nakagawa
Hiromichi Matsuoka*
Affiliation:
Department of Medical Oncology, Division of Psychosomatic Medicine, Kinki University Faculty of Medicine, Osaka, Japan
Kazuhiro Yoshiuchi
Affiliation:
Department of Stress Sciences and Psychosomatic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Atsuko Koyama
Affiliation:
Department of Medical Oncology, Division of Psychosomatic Medicine, Kinki University Faculty of Medicine, Osaka, Japan
Masatomo Otsuka
Affiliation:
Department of Palliative Care Medicine, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan
Kazuhiko Nakagawa
Affiliation:
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan
*
Address correspondence and reprint requests to: Hiromichi Matsuoka, Department of Medical Oncology, Division of Psychosomatic Medicine, Kinki University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka Sayama City, Osaka, 589-8511, Japan. E-mail: matsuoka_h@med.kindai.ac.jp
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Delirium is a frequently encountered psychiatric disease in terminal cancer patients. However, the mechanism of delirium is unclear. The aim of our study was to investigate the relationship between administration of chemotherapy drugs that penetrate the blood–brain barrier (BBB) and the development of delirium in cancer patients.

Method:

We retrospectively analyzed 166 cancer patients (97 males, 69 females) continuously who died between September of 2007 and January of 2010 using a review of medical charts. Multiple logistic regression analysis was employed to investigate the effects of antineoplastic drugs penetrating the BBB on development of delirium in cancer patients with control for other risk factors.

Results:

In multivariate analysis, antineoplastic drugs that penetrated the BBB were significantly associated with development of delirium (OR = 18.92, CI95 = 1.08–333.04, p < 0.001).

Significance of results:

The use of chemotherapy drugs that penetrate the BBB may be a risk factor for delirium. This information may allow palliative care doctors and medical oncologists to predict which patients are at increased risk for delirium.

Keywords

Cancer patientsChemotherapeutic drugsDeliriumBlood–brain barrierP glycoprotein
Type
Original Articles
Information
Palliative & Supportive Care , Volume 13 , Issue 4 , August 2015 , pp. 859 - 864
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Allen, J.C. & Rosen, G. (1978). Transient cerebral dysfunction following chemotherapy for osteogenic sarcoma. Annals of Neurology, 3, 441–444.CrossRefGoogle ScholarPubMed
American Psychiatric Association (APA) (2000). Diagnostic and statistical manual of mental disorders, 4th ed. [DSM–IV–TR]. Washington, DC: American Psychiatric Press.Google Scholar
Argyriou, A.A., Assimakopoulos, K., Iconomou, G., et al. (2010). Either called “chemobrain” or “chemofog,” the long-term chemotherapy-induced cognitive decline in cancer survivors is real. Journal of Pain and Symptom Management, 41, 126–139.CrossRefGoogle ScholarPubMed
Berman, I.J. & Mann, M.P. (1980). Seizures and transient cortical blindness associated with cis-platinum (II) diamminedichloride (PDD) therapy in a thirty-year-old man. Cancer, 45, 764–766.3.0.CO;2-G>CrossRefGoogle Scholar
Brunner, K.W. & Young, C.W. (1965). A methylhydrazine derivative in Hodgkin's disease and toxic effects studied in 51 patients. Annals of Internal Medicine, 63, 69–86.CrossRefGoogle ScholarPubMed
Clouston, P.D., de Angelis, L. & Posner, J.B. (1992). The spectrum of neurological disease in patients with systemic cancer. Annals of Neurology, 31, 268–273.CrossRefGoogle ScholarPubMed
Cordon-Cardo, C., O'Brien, J.P., Casals, D., et al. (1989). Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood–brain barrier sites. Proceedings of the National Academy of Sciences of the United States of America, 86, 695–698.CrossRefGoogle ScholarPubMed
Ekenel, M., Hormigo, A.M., Peak, S., et al. (2007). Capecitabine therapy of central nervous system metastases from breast cancer. Journal of Neuro-Oncology, 85, 223–227.CrossRefGoogle ScholarPubMed
Falleti, M.G., Sanfilippo, A., Maruff, P., et al. (2005). The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: A meta-analysis of the current literature. Brain and Cognition, 59, 60–70.CrossRefGoogle ScholarPubMed
Frei, E. III, Franzino, A., Shnider, B.I., et al. (1961). Clinical studies of vinblastine. Cancer Chemotherapy Reports, 12, 125–129.Google ScholarPubMed
Gaudreau, J.D., Gagnon, P., Harel, F., et al. (2005). Psychoactive medications and risk of delirium in hospitalized cancer patients. Journal of Clinical Oncology, 23, 6712–6718.CrossRefGoogle ScholarPubMed
Greenwald, E.S. (1976). Organic mental changes with fluorouracil therapy. The Journal of the American Medical Association, 235, 248–249.CrossRefGoogle ScholarPubMed
Heim, M.E., Fiene, R. & Schick, E. (1981). Central nervous side effects following ifosfamide monotherapy of advanced renal carcinoma. Journal of Cancer Research and Clinical Oncology, 100, 113–116.CrossRefGoogle ScholarPubMed
Hermelink, K., Untch, M., Lux, M.P., et al. (2007). Cognitive function during neoadjuvant chemotherapy for breast cancer: Results of a prospective, multicenter, longitudinal study. Cancer, 109, 1905–1913.CrossRefGoogle ScholarPubMed
Holland, J.F., Scharlau, C., Gailani, S., et al. (1973). Vincristine treatment of advanced cancer: A cooperative study of 392 cases. Cancer Research, 33, 1258–1264.Google Scholar
Holland, J.F,, Fasanello, S. & Ohnuma, T. (1974). Psychiatric symptoms associated with L-asparaginase administration. Journal of Psychiatric Research, 10, 105–113.Google ScholarPubMed
Inouye, S.K., Viscoli, C.M., Horwitz, R.I., et al. (1993). A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Annals of Internal Medicine, 119, 474–481.CrossRefGoogle ScholarPubMed
Jansen, C.E., Miaskowski, C., Dodd, M., et al. (2005). A meta-analysis of studies of the effects of cancer chemotherapy on various domains of cognitive function. Cancer, 104, 2222–2233.CrossRefGoogle Scholar
Lawlor, P.G., Gagnon, B., Mancini, I.L., et al. (2000). Occurrence, causes, and outcome of delirium in patients with advanced cancer: A prospective study. Archives of Internal Medicine, 160, 786–794.CrossRefGoogle ScholarPubMed
Levine, P.M., Silberfarb, P.M. & Lipowski, Z.J. (1978). Mental disorders in cancer patients: A study of 100 psychiatric referrals. Cancer, 42, 1385–1391.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Lin, N.U., Bellon, J.R. & Winer, E.P. (2004). CNS metastases in breast cancer. Journal of Clinical Oncology, 22, 3608–3617.CrossRefGoogle ScholarPubMed
Massie, M.J., Holland, J.C. & Glass, E. (1983). Delirium in terminally ill cancer patients. The American Journal of Psychiatry, 140, 1048–1050.Google ScholarPubMed
Priestman, T.J. (1980). Initial evaluation of human lymphoblastoid interferon in patients with advanced malignant disease. Lancet, 2, 113–118.CrossRefGoogle ScholarPubMed
Silberfarb, P.M. (1983). Chemotherapy and cognitive defects in cancer patients. Annual Review of Medicine, 34, 35–46.CrossRefGoogle ScholarPubMed
Stewart, A., Bielajew, C., Collins, B., et al. (2006). A meta-analysis of the neuropsychological effects of adjuvant chemotherapy treatment in women treated for breast cancer. Clinical Neuropsychology, 20, 76–89.CrossRefGoogle ScholarPubMed
Stolinsky, D.C., Solomon, J., Pugh, R.P., et al. (1974). Clinical experience with procarbazine in Hodgkin's disease, reticulum cell sarcoma, and lymphosarcoma. Cancer, 26, 984–990.3.0.CO;2-E>CrossRefGoogle Scholar
Ueno, M. (2009). Mechanisms of the penetration of blood-borne substances into the brain. Current Neuropharmacology, 7, 142–149.CrossRefGoogle ScholarPubMed
Wefel, J.S., Lenzi, R., Theriault, R.L., et al. (2004). The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: Results of a prospective, randomized, longitudinal trial. Cancer, 100, 2292–2299.CrossRefGoogle ScholarPubMed
Wong, E.T. & Berkenblit, A. (2004). The role of topotecan in the treatment of brain metastases. The Oncologist, 9, 68–79.CrossRefGoogle ScholarPubMed
Yamada, K., Bremer, A.M, & West, C.R. (1979). Intra-arterial BCNU therapy in the treatment of metastatic brain tumor from lung carcinoma. Cancer, 44, 2000–2007.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Zeevi, N., Pachter, J., McCullough, L.D., et al. (2010). The blood–brain barrier: Geriatric relevance of a critical brain–body interface. Journal of the American Geriatrics Society, 58, 1749–1757.CrossRefGoogle ScholarPubMed