APOS Clinical E-Mail Update #2
2 September 2003
In this Update:
What is the outlook for survivors of childhood cancer?
Ross L, Johansen C, Dalton SO, Mellemkjaer L, Thomassen LH et al. Psychiatric hospitalizations among survivors of cancer in childhood or adolescence. N Engl J Med 2003;349:650-657.
Researchers in Denmark capitalized on the capacity to link the Danish Cancer Registry with the Danish Psychiatric Central Register. They found a cohort of 3710 survivors of childhood and adolescent cancer with up to 24 years of follow-up and were able to assess whether they had psychiatric hospitalizations. Children who had brain tumors accounted for most of the increased risk of psychiatric hospitalization among childhood cancer survivors. The ratio of observed to expected cases of hospitalization for psychiatric disease among survivors was 1.8. No evidence of significantly increased risk of major depression was noted.
Of 11 brain tumor survivors who were later hospitalized for schizophrenia, 3 were noted to have a familial predisposition to psychosis. While there were two survivors of acute lymphoblastic leukemia who were later diagnosed with schizophrenia, these two had not had radiation treatment to the brain. The use of radiation treatment to the brain did not increase the risk of schizophrenia overall.
This study suggests that children who survive cancer do not have significant increases in psychiatric disorder unless they had brain tumors. In general, they support the importance of biological rather than psychological contributions to psychopathology. - DBG
Ching-Hon P, Cheng C, Leung W, Rai SN, Rivera GK et al. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 2003;349:640-649.
It is unusual for two papers on psychological aspects of oncology to lead in one issue of the New England Journal, but this study of childhood survivors of acute lymphoblastic leukemia (ALL) was published with the citation mentioned above. The study reviewed 856 patients treated between 1962 and 1992 in clinical trials at St. Jude Children’s Research Hospital in Memphis TN. They found that survivors of childhood ALL who have lived 10 years or more without adverse event have a normal long-term survival. Those who had received radiation therapy had a greater risk of unemployment, second neoplasms, and a slight excess in mortality. The majority of the second neoplasms occurred within or adjacent to the field of cranial or craniospinal irradiation. Women in the group that received radiation were less apt to marry than the age-matched population. The rate of unemployment was also slightly higher for women in the irradiated group. They note that adult survivors of childhood cancer have been reported to have lower marriage rates, particularly if they have had brain tumors. 84% of patients responded to the questionnaire. - DBG
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What are New Angles on Chemotherapy-induced Nausea?
Guttuso T, Roscoe J, Griggs J. Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Lancet 2003; 361:1703-05.
Gabapentin may be a drug that can reduce delayed nausea in the setting of chemotherapy. These researchers explored the possibility further after they had a patient with breast cancer receiving cyclophosphamide and doxorubicin whose nausea improved when gabapentin 300 mg t.i.d. was added to the regimen. They had originally given gabapentin as a treatment for hot flashes.1
They continued with an open-label pilot study of 21 patients with breast cancer who were naïve to chemotherapy before receiving 4 cycles of cyclophosphamide and doxorubicin. They pre-treated with gabapentin for cycles 2 and 4 not 1 and 3. They selected those who had severe nausea after the first treatment in spite of treatment with ondansetron, lorazepam, and dexamethasone. Gabapentin dosing began 5 days before chemotherapy 300 mg h.s. for 2 days and b.i.d. for 2 days. They found that there were median reductions in peak acute and delayed (2-5 days after chemotherapy) nausea. For those with some nausea on 300 mg t.i.d., they increased the dose to 600 t.i.d.
This report is notable for the possibility that gabapentin has a role in reducing delayed chemotherapy-induced nausea. The authors suggest that gabapentin may lessen tachykinin neurotransmitter activity. It has been noted that a selective tachykinin receptor antagonist can reduce both acute and delayed nausea from chemotherapy.2
- Guttuso T, Kurlan R, McDermott M, Kieburtz K. Gabapentin’s effects on hot flushes in postmenopauseal women: a randomized controlled trial. Obstet Gynecol 2003;101:337-345.
- Navari RM, Reinhardt RR, Gralla RJ et al. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030. antiemetic Trials Group. N Engl J Med 1999;340:190-95.
Tremblay P B, Kaiser R, Sezer O, et al. Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients. J Clin Oncol 2003; 21: 2147-2155.
Ondansetron and other 5-HT3 antagonists have been a boon to oncology patients. They prevent chemotherapy-induced vomiting in 70% of patients. This article explores the pharmacogenetics of the group of patients who do not respond. The researchers thought that genetic variations in the 5-HT3B receptor gene may explain the relative ineffectiveness of these drugs in some patients. In the 30% of patients who did have nausea or vomiting with chemotherapy despite tropisetron or ondansetron treatment, they found 13 polymorphisms and two deletion variants. They have previously shown that ultra-rapid metabolizers for CYP2D6 had the highest score of vomiting and nausea with tropisetron; poor metabolizers had higher levels of the anti-emetic. They found that patients homozygous for the --100_--102AGG deletion variant of the 5-HT3B receptor gene and ultra-rapid metabolizers of ondansetron or tropisetron showed the highest intensity of vomiting and nausea. The frequency of the deletion variant was only 1.3% and the frequency of ultra-metabolizers only 1-2%, so only a small portion of the resistance to this treatment has been explained.—DBG
Montgomery GH, Bovbjerg DH. Expectations of chemotherapy-related nausea: Emotional and experiential predictors, Ann Behav Med 2003, 25:48-54.
In a sample of 80 breast cancer patients undergoing adjuvant chemotherapy, researchers investigated whether concurrent emotional distress or prior experience with post-treatment nausea was a contributor to expectations of post-treatment nausea. Patients were diagnosed with early-stage breast cancer and had not previously received radiotherapy or chemotherapy. All patients received uniform anti-emetic treatment. Concurrent emotional distress prior to the first infusion showed a tendency to be a predictor of expectations of post-treatment nausea. Not surprisingly, after the first infusion, patients’ expectations about post-treatment nausea were strongly influenced by prior experiences with chemotherapy-related nausea. Concurrent distress did not account for patients’ expectations about post-treatment nausea. – KD
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What makes colorectal screening more appealing?
Wardle J, Williamson S, McCaffery K, Sutton S, Taylor T, Edwards R, Atkins W. Increasing Attendance at Colorectal Cancer Screening: Testing the Efficacy of a Mailed, Psychoeducational Intervention in a Community Sample of Older Adults, Health Psychol 2003, 22:99-105.
In order to modify negative attitudes toward flexible sigmoidoscopy, researchers
conducted a randomized controlled trial among 2,966 adults ages 55-64 to evaluate the efficacy of a mailed booklet that presented basic factual information about colorectal cancer and screening.
The booklet was designed using components of the health belief model, regret theories, and the theory of planned behavior’s efficacy for going to a screening and social norms. The booklet addressed perceived barriers to the test and attempted to increase positive expectations about the test. The booklet followed a questions-and-answers format about screening. These were presented as humorous cartoon strips depicting brief conversations between family members and friends. Quotations from trial participants who had already undergone screening were included. Pilot studies revealed that 93% of respondents were less worried about flexible sigmoidoscopy after reading the booklet.
Overall, individuals who received the intervention ‘were less likely to perceive flexible sigmoidoscopy as painful and embarrassing, were less fatalistic or afraid, and felt better able to ask someone to accompany them to the screening’. The intervention group also anticipated a more positive experience; that is, they anticipated feeling better if they underwent sigmoidoscopy, whatever the result. Compared to those who received the standard screening invitation, the intervention group had a 3.6% higher attendance level at screening. This study demonstrates that creative approaches to the design of interventions to increase screening behavior may be effective in modifying negative attitudes toward screening. – KD
Wardle J, Williamson S, Sutton S, Biran A, McCaffery K, Cuzick J, Atkin W. Psychological impact of colorectal cancer screening, Health Psychol 2003, 22:54-59.
Researchers examined the psychological impact of flexible sigmoidoscopy screening, a relatively new means of cancer screening in the UK, as part of the large-scale UK Flexible Sigmoidoscopy Screening Trial. The first study examined participants’ psychological well-being three months after screening. The second examined changes in psychological functioning from baseline to three months after screening in a randomly selected subset of participants.
Predictably, worry about bowel cancer was higher in the higher risk group relative to the low-risk and negative risk group. There were no group differences in state anxiety, well-being, reported bowel symptoms, or perceived bowel cancer risk. When changes over time were examined, cancer worry, state anxiety, and reported bowel symptoms were significantly reduced after screening. Those who initially reported higher levels of anxiety and those with higher pre-screening perceived risk showed the greatest reductions in worry.
The researchers were reassured that there were no significant psychological costs associated with obtaining screening results. For some patients, obtaining their screening results appeared to reduce the psychological costs of screening. – KD
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DBG: Donna B. Greenberg, MD, Associate Professor of Psychiatry at Harvard Medical School and Psychiatric Consultant in the Massachusetts General Hospital Cancer Center, Dana Farber Partners Cancer Care
KD: Kristine Donovan, PhD, MBA, Postdoctoral Research Fellow, Moffitt Cancer Center at the University of South Florida