Neuroprotective effect of paroxetine hydrochloride among 781 cancer patients receiving chemotherapy: A URCC CCOP study

Reviewer: Christine Hill-Kayser, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 3, 2009

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Presenter: Pascal Jean-Pierre, PhD, MPH
Presenter's Affiliation: University of Rochester Medical Center
Type of Session: Scientific

Background

  • A large number of cancer survivors, ranging from 17-75% in various studies, report difficulties with attention, memory, and other aspects of neurocognitive function after completion of cancer treatments. Most commonly, survivors complain of difficulties with multi-tasking and concentrating, as well as a feeling of generalized cognitive “slowing” and increased required mental effort for routine tasks. Unfortunately, changes in memory and attention may be pervasive and persistent, and may have negative and significant impact on quality of life of cancer survivors. Specific cancer-related cognitive changes may include:
    • Impairment in attention
    • Impairment in memory
      • Specifically, difficulty in memory retrieval and restriction in working memory
    • Processing speed dysfunction, particularly with information conversion
    • Executive dysfunction
      • May include difficulty with planning, decision-making, and abstract thinking
  • Sometimes referred to as “chemobrain,” cognitive issues following cancer treatment are likely multifactorial in nature. Current theories regarding pathophysiology of changes in cognitive function include:
    • Genetic predisposition
    • Toxic neuropsychiatric effects of chemotherapy, both direct and indirect
    • Effects of chemotherapy on neurogenesis
    • Hormonal effects of cancer treatments (chemotherapies, hormonal-modulators, brain radiotherapy and surgery)
    • Central nervous system cytokine activity
    • Involvement of other symptoms on quality of life, including pain, depression, fatigue, and fear of progression
  • Despite the apparent prominence of cancer-related cognitive dysfunction in the survivor population, a relative paucity of data regarding interventions is available.
  • The study described here was undertaken with the intent of assessing the impact of paroxetine (Paxil) as a pharmacologic intervention in treatment of cancer-related cognitive dysfunction, defined as problems in attention and memory reported by cancer patients.

Materials and Methods

  • Participants were selected from a group of patients undergoing cancer treatment. Eligibility criteria included the following:
    • Patients were required to have a cancer diagnosis, and to be planned to receive at least four cycles of chemotherapy without interruption for radiation or other medications. Planned chemotherapy cycles were required to be planned to be separated from one another by at least three weeks.
    • Patients were required to be at least 18 years of age, able to swallow medications, and have adequate renal, hepatic, and cardiac function.
    • Pregnancy, breast feeding, previous hospitalization for psychiatric conditions, and treatment with psychotropic medication in the past 14 days were exclusionary criteria.
  • Memory problems were assessed using the Brief Screening Measure of Attention and Memory Problems Related to Cancer (BSMAM-Ca).
    • Reliability assessment revealed α = 0.90 for this assessment.
    • Measures included:
      • “I am apt to forget things.”
      • “I cannot concentrate.”
      • “It is difficult to think.”
      • “My brain feels muddled.”
      • “My head feels heavy.”
  • Depression was assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale.
  • Repeated measure ANOVA and t-tests were conducted to assess changes in average BSMAM-Ca scores and effects of treatment versus placebo.

Results

  • 781 total patients were enrolled, and were randomized to receive daily paroxetine hydrochloride versus placebo. Characteristics of the two groups were very similar:
    • Mean age was 56.5 years in the study group, and 56.3 in the control group (range 27-87 and 23-84 years, respectively).
    • 80% of study individuals were female compared to 71% of controls.
    • 55% of study individuals had attended some college, compared to 51% of controls. 45% of each group had attended only high school.
    • 70% of study individuals were married versus 71% of controls.
    • Primary cancer diagnoses were similar between the two groups, with breast cancer being the most common (57% of study individuals and 50% of controls), followed by lung (14% versus 13%, respectively), hematologic (12% versus 15%, respectively), and gynecologic (7% versus 9%).
  • Initial assessment using BSMAM-Ca was performed after the first chemotherapy cycle, prior to initiation of paroxetine/placebo therapy. Repeat assessments were performed following the fourth chemotherapy cycle.
  • Patients receiving paroxetine reported more improvement in attention and memory than those receiving placebo (p < 0.05).
  • This effect remained statistically significant when depression was controlled for.

Author's Conclusions

  • The authors note that cancer-related cognitive dysfunction is a serious problem for cancer patients and survivors.
  • They conclude from their study that patients taking paroxetine hydrochloride report greater improvement in cognitive function than those taking a placebo drug, even after controlling for depression.

Clinical/Scientific Implications

  • “Chemobrain” or subjective cognitive dysfunction following cancer treatment is a common complaint among cancer survivors.
  • At this point, its pathogenesis is poorly understood, and is all likelihood multifactorial in nature.
  • The authors have made an important first step in attempting intervention with paroxetine, and selective serotonin reuptake inhibitor, as treatment for cancer-related cognitive dysfunction.
  • Although the authors have attempted to control for depression in their assessment, the role of anxiety/depression in cancer-related cognitive dysfunction is certainly a potential confounding factor. This is particularly true for the study described here, when the intervention and assessments were performed in the acute setting during which patients received chemotherapy.
  • Along these lines, longer term data, with assessments carried out 6 – 12 months after completion of cancer treatments would certainly be of interest.
  • Having said this, the authors have made an important first step in evaluating the potential role of paroxetine in managing cancer-related cognitive dysfunction. Their results are hypothesis-driving, and longer-term studies are warranted.

See Patient Summary


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