- Email: [email protected]
Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction
604
Journal of Pain and Symptom Management
Vol. 44 No. 4 October 2012
Clinical Note
Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction Keisuke Kaneishi, MD, PhD, Masahiro Kawabata, MD, PhD, and Tatsuya Morita, MD Department of Palliative Care Unit (K.K., M.K.), Tokyo Kosei Nenkin Hospital, Tokyo; and Department of Palliative and Supportive Care, Palliative Care Team, and Seirei Hospice (T.M.), Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
Abstract Bowel obstruction is one of the most common complications in patients with advanced cancer. Incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment to quality of life. We explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction. This retrospective study was carried out on a palliative care unit, using an electronic medical record from 2007 to 2009. The intensity of the symptom was evaluated and classified from the medical records on four scales. The frequency of vomiting also was noted from the medical records. During this study period, 20 patients met the inclusion criteria. The average dose of olanzapine was 4.9 1.2 mg and treatment duration was 23.4 16.2 days. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4 0.7 to 0.2 0.4 (P < 0.001). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea. The average frequency of vomiting significantly decreased after olanzapine treatment from 1.1 1.3 times/day (median 0.5; range 0e4) before the treatment to 0.3 0.5 times/day (median 0; range 0e1) after the treatment (P < 0.01). Before the treatment, 10 patients experienced vomiting; eight of these patients experienced a decrease in the frequency of vomiting with olanzapine treatment. Our study suggests the potential efficacy of olanzapine for relief of nausea in incomplete bowel obstruction. A prospective trial is promising. J Pain Symptom Manage 2012;44:604e607. Ó 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Olanzapine, incomplete bowel obstruction, nausea, vomiting, advanced cancer
Introduction Address correspondence to: Keisuke Kaneishi, MD, PhD, Department of Palliative Care Unit, Tokyo Kosei Nenkin Hospital, 5e1 Tsukudoecho, Shinjuku, Tokyo 162e0815, Japan. E-mail: [email protected] Accepted for publication: October 27, 2011. Ó 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Bowel obstruction is one of the most common complications in patients with advanced cancer, occurring in 5.5e42% of ovarian cancers, 4.4e24% of rectal cancers, and 3e15% of breast and lung cancers. In cancer patients, compression of the bowel lumen develops 0885-3924/$ - see front matter doi:10.1016/j.jpainsymman.2011.10.023
Vol. 44 No. 4 October 2012
Olanzapine for Nausea in Bowel Obstruction
gradually and often remains partial.1 Subsequently, incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment in quality of life. It is important to assess the causes of such symptoms for their appropriate management.2 Generally, nausea and vomiting related to inoperative and incomplete bowel obstruction are controlled through pharmacological treatment, including metoclopramide, haloperidol, and cyclizine.3,4 However, these standard medications are often ineffective and may lead to complicated and uncomfortable adverse effects. For example, metoclopramide and haloperidol have been strongly associated with a number of drug-induced movement disorders (colic pain) and extrapyramidal symptoms, respectively.5 Therefore, it is desirable to identify other drugs with improved therapeutic efficacy for nausea and vomiting with relatively few side effects in incomplete bowel obstruction. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors, including dopaminergic (D1, D2, D3, and D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, and 5-HT6), muscarinic (m1, m2, m3, and m4), histaminergic (H1), and adrenergic (alpha1) receptors.6 These receptors are present in the chemoreceptor trigger zone as well as the vomiting center; therefore, olanzapine has potentially broad antiemetic capabilities.7 Previous studies have suggested that olanzapine may be efficacious in the treatment of nausea related to multiple sources, especially chemotherapy-related nausea, with relatively few side effects.8e11 However, the treatment efficacy of olanzapine in patients with bowel obstruction has, to the best of our knowledge, not been reported thus far. In this retrospective study, we explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction.
Methods This retrospective study was carried out at the palliative care unit of Tokyo Kosei Nenkin Hospital. We reviewed the electronic medical records of patients admitted from 2007 to 2009 who fulfilled the following inclusion criteria: 1) patients with advanced cancer and 2) patients
605
who received olanzapine for relief of nausea and vomiting resulting from incomplete bowel obstruction. Incomplete bowel obstruction was clinically diagnosed on the basis of physical and/or radiological examinations. The medical indications for olanzapine in these patients during this study period were as follows: insufficient management with previous antiemetic treatment (metoclopramide, steroids, haloperidol, domperidone, chlorpromazine, and/or prochlorperazine). The exclusion criteria for this study were 1) any indication for palliative surgery, 2) presence of diabetes mellitus, and 3) need for nasogastric intubation. Patient medical records were reviewed retrospectively and checked by two physicians (palliative care specialists). These two reviewers independently collected data, and any inconsistencies between the reviewers were resolved by discussion. Data for demographic variables, disease site, dosage and dosing period of olanzapine, and adverse side effects were collected. Nausea and side effects were assessed daily by nurses for all patients; we retrospectively reviewed patient charts at the point before starting treatment with olanzapine and for three days after administration of the drug. The average grade of each symptom before and after the administration of the drug was compared. The intensity of each symptom was evaluated and classified based on the description in the patient charts and translated retrospectively as four scales (scores) as follows: none (0), mild (1), moderate (2), and severe (3). The frequency of vomiting also was noted from the medical records.
Statistical Analysis
The results are expressed as mean SD. The differences between groups were analyzed by the Wilcoxon-signed rank test.
Results During the study period, 338 patients were admitted to the palliative care unit of our hospital; of these, 20 patients met our inclusion criteria. The group comprised 13 women and seven men, with an average age of 64.7 14.9 years (range 35e90 years). Patients were diagnosed with incomplete bowel obstruction in the upper (n ¼ 11) and lower (n ¼ 9) intestines. Primary tumor sites included the
606
Kaneishi et al.
stomach (n ¼ 4), colon/rectum (n ¼ 4), uterus/ovary (n ¼ 3), lung (n ¼ 2), bile duct (n ¼ 2), urinary tract (n ¼ 2), esophagus (n ¼ 1), pancreas (n ¼ 1), and peritoneum (n ¼ 1). The average dose of olanzapine was 4.9 1.2 mg (median 5.0; range 2.5e7.5), and the average treatment duration was 23.4 16.2 days (median 21; range 2e60). During the same period, a steroid (betamethasone) had been administered before olanzapine treatment to 12 patients; the average dose of betamethasone was 3.5 2.1 mg (median 3.0; range 0.5e8), and no other antiemetic drugs were used. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4 0.7 to 0.2 0.4 (P < 0.001). The percentage of patients with none or mild nausea was 10% before olanzapine treatment; 100% of the patients experienced no or mild nausea after the treatment (Table 1). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea; no patient experienced worsening of the symptom. The average frequency of vomiting significantly decreased with olanzapine treatment from 1.1 1.3 times/day (median 0.5; range 0e4) before the treatment to 0.3 0.5 times/day (median 0; range 0e1) after the treatment (P < 0.01). Before the treatment, 10 patients experienced vomiting; eight (80%) of these patients experienced a decrease in the frequency of vomiting after the treatment. Adverse effects of olanzapine treatment included drowsiness (n ¼ 2) and dizziness (n ¼ 1). However, none of these patients chose Table 1 Change in Intensity of Nausea and Frequency of Vomiting With Olanzapine Treatments Nausea None Mild Moderate Severe Vomiting (per day) 0 1 2 3 4
Before
After
0 2 9 9
16 4 0 0
10 3 4 2 1
14 6 0 0 0
Vol. 44 No. 4 October 2012
to stop the antiemetic olanzapine treatment for these reasons. These symptoms were treated as clinical or diagnostic observations only, and the need for intervention was not indicated in any of these patients.
Discussion This study is, to our best knowledge, the first study to investigate the antiemetic activity of olanzapine in patients with inoperable and incomplete bowel obstruction. Our findings revealed that olanzapine successfully reduced the intensity of nausea and the frequency of vomiting caused by incomplete bowel obstruction. Olanzapine has been reported to be efficacious against nausea and vomiting associated with delayed emesis after chemotherapy8,11 in patients with advanced cancer.9,10 A previous study demonstrated a 39.2% improvement in chemotherapy-induced nausea by the addition of olanzapine treatment.11 Nausea relief in bowel obstruction after steroid therapy has been reported in approximately 68% of patients vs. 33% of placebo-treated patients.12 Our results were thus comparable in the effectiveness of olanzapine as an antiemetic. The other important finding of this study was that the drug was administered without any serious adverse events. Other studies also have reported that in patients with advanced cancer, olanzapine can be used with relatively few side effects9,10 and fewer drug interactions as compared with other neuroleptic agents.6 It is partly because olanzapine has five times the affinity for 5-HT2 receptors than for D2 receptors, resulting in fewer extrapyramidal side effects. However, insulin-resistant diabetes and neuroleptic malignant syndrome, although rarely reported, are possible consequences of olanzapine treatment.13 Antiemetics can be administered by various routes; medication can be tailored to each patient with regard to both compliance and the route of administration. Olanzapine (ZydisÒ) is available as an orally disintegrating disk, which can be easily administered, even to patients with nausea and vomiting. Our study had certain limitations, including the inherent limitations of a retrospective study. Furthermore, it was a single-center study with a small sample size; it lacked a control group. It
Vol. 44 No. 4 October 2012
Olanzapine for Nausea in Bowel Obstruction
is possible that the relief of nausea and vomiting might have occurred as a part of the natural course of the disease or as the result of a placebo effect in a certain percentage of patients. Generally, causes of nausea and vomiting in patients with advanced cancer are multifactorial; factors other than incomplete bowel obstruction might have partially affected these symptoms. Next, the possibility of differences in the evaluation of nausea and vomiting cannot be ruled out. Patients may have underreported the symptoms because of potential recall bias, and physicians and nurses may have failed to document them for multiple reasons, especially because no structured tools or protocols were used during record keeping. Thus, we realize that our results are clearly tentative; nonetheless, we consider that the high percentage of patients who experienced symptomatic relief (90%) demonstrates the potential of olanzapine as an effective antiemetic in cancer patients with incomplete bowel obstruction. In conclusion, our results suggest the potential efficacy of olanzapine for nausea relief in incomplete bowel obstruction. Further prospective trials, including randomized controlled trials with a placebo-controlled design and comparison with an established antiemetic, are required for validating these results.
Disclosures and Acknowledgments No funding was received for this study, and the authors declare no conflicts of interest.
References 1. Ripamonti C, Twycross R, Baines M, et al. Clinical practice recommendations for the management of bowel obstruction in patients with endestage cancer. Support Care Cancer 2001;9:223e233. 2. Davis MP, Hallerberg G. A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage 2010;39:756e767.
607
3. Fainsinger RL, Spachynski K, Hanson J, Breura E. Symptom control in terminally ill patients with malignant bowel obstruction (MBO). J Pain Symptom Manage 1994;9:12e18. 4. Baines M, Oliver DJ, Carter RL. Medical management of intestinal obstruction in patients with advanced malignant disease. A clinical and pathological study. Lancet 1985;2:990e993. 5. Tonini M, Cipollina L, Poluzzi E, et al. Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 2004;19:379e390. 6. Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 1999;37: 177e193. 7. Davis MP, Khawam E, Pozuelo L, Lagman R. Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project. Expert Rev Anticancer Ther 2002;2:365e376. 8. Passik SD, Kirsh KL, Theobald DE, et al. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Symptom Manage 2003;25:485e488. 9. Passik SD, Lundberg J, Kirsh KL, et al. A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 2002;23:526e532. 10. Srivastava M, BritoeDellan N, Davis MP, Leach M, Lagman R. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 2003;25:578e582. 11. Tan L, Liu J, Liu X, et al. Clinical research of olanzapine for prevention of chemotherapye induced nausea and vomiting. J Exp Clin Cancer Res 2009;28:131. 12. Laval G, Girardier J, Lassauni ere JM, et al. The use of steroids in the management of inoperable intestinal obstruction in terminal cancer patients: do they remove the obstruction? Palliat Med 2000;14: 3e10. 13. Ishigooka J, Murasaki M, Miura S. The olanzapine earlyephase II study group. Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia: results of an openelabel multicenter study in Japan. Psychiatry Clin Neurosci 2001;55:353e363.
Journal of Pain and Symptom Management
Vol. 44 No. 4 October 2012
Clinical Note
Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction Keisuke Kaneishi, MD, PhD, Masahiro Kawabata, MD, PhD, and Tatsuya Morita, MD Department of Palliative Care Unit (K.K., M.K.), Tokyo Kosei Nenkin Hospital, Tokyo; and Department of Palliative and Supportive Care, Palliative Care Team, and Seirei Hospice (T.M.), Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
Abstract Bowel obstruction is one of the most common complications in patients with advanced cancer. Incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment to quality of life. We explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction. This retrospective study was carried out on a palliative care unit, using an electronic medical record from 2007 to 2009. The intensity of the symptom was evaluated and classified from the medical records on four scales. The frequency of vomiting also was noted from the medical records. During this study period, 20 patients met the inclusion criteria. The average dose of olanzapine was 4.9 1.2 mg and treatment duration was 23.4 16.2 days. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4 0.7 to 0.2 0.4 (P < 0.001). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea. The average frequency of vomiting significantly decreased after olanzapine treatment from 1.1 1.3 times/day (median 0.5; range 0e4) before the treatment to 0.3 0.5 times/day (median 0; range 0e1) after the treatment (P < 0.01). Before the treatment, 10 patients experienced vomiting; eight of these patients experienced a decrease in the frequency of vomiting with olanzapine treatment. Our study suggests the potential efficacy of olanzapine for relief of nausea in incomplete bowel obstruction. A prospective trial is promising. J Pain Symptom Manage 2012;44:604e607. Ó 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Olanzapine, incomplete bowel obstruction, nausea, vomiting, advanced cancer
Introduction Address correspondence to: Keisuke Kaneishi, MD, PhD, Department of Palliative Care Unit, Tokyo Kosei Nenkin Hospital, 5e1 Tsukudoecho, Shinjuku, Tokyo 162e0815, Japan. E-mail: [email protected] Accepted for publication: October 27, 2011. Ó 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Bowel obstruction is one of the most common complications in patients with advanced cancer, occurring in 5.5e42% of ovarian cancers, 4.4e24% of rectal cancers, and 3e15% of breast and lung cancers. In cancer patients, compression of the bowel lumen develops 0885-3924/$ - see front matter doi:10.1016/j.jpainsymman.2011.10.023
Vol. 44 No. 4 October 2012
Olanzapine for Nausea in Bowel Obstruction
gradually and often remains partial.1 Subsequently, incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment in quality of life. It is important to assess the causes of such symptoms for their appropriate management.2 Generally, nausea and vomiting related to inoperative and incomplete bowel obstruction are controlled through pharmacological treatment, including metoclopramide, haloperidol, and cyclizine.3,4 However, these standard medications are often ineffective and may lead to complicated and uncomfortable adverse effects. For example, metoclopramide and haloperidol have been strongly associated with a number of drug-induced movement disorders (colic pain) and extrapyramidal symptoms, respectively.5 Therefore, it is desirable to identify other drugs with improved therapeutic efficacy for nausea and vomiting with relatively few side effects in incomplete bowel obstruction. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors, including dopaminergic (D1, D2, D3, and D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, and 5-HT6), muscarinic (m1, m2, m3, and m4), histaminergic (H1), and adrenergic (alpha1) receptors.6 These receptors are present in the chemoreceptor trigger zone as well as the vomiting center; therefore, olanzapine has potentially broad antiemetic capabilities.7 Previous studies have suggested that olanzapine may be efficacious in the treatment of nausea related to multiple sources, especially chemotherapy-related nausea, with relatively few side effects.8e11 However, the treatment efficacy of olanzapine in patients with bowel obstruction has, to the best of our knowledge, not been reported thus far. In this retrospective study, we explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction.
Methods This retrospective study was carried out at the palliative care unit of Tokyo Kosei Nenkin Hospital. We reviewed the electronic medical records of patients admitted from 2007 to 2009 who fulfilled the following inclusion criteria: 1) patients with advanced cancer and 2) patients
605
who received olanzapine for relief of nausea and vomiting resulting from incomplete bowel obstruction. Incomplete bowel obstruction was clinically diagnosed on the basis of physical and/or radiological examinations. The medical indications for olanzapine in these patients during this study period were as follows: insufficient management with previous antiemetic treatment (metoclopramide, steroids, haloperidol, domperidone, chlorpromazine, and/or prochlorperazine). The exclusion criteria for this study were 1) any indication for palliative surgery, 2) presence of diabetes mellitus, and 3) need for nasogastric intubation. Patient medical records were reviewed retrospectively and checked by two physicians (palliative care specialists). These two reviewers independently collected data, and any inconsistencies between the reviewers were resolved by discussion. Data for demographic variables, disease site, dosage and dosing period of olanzapine, and adverse side effects were collected. Nausea and side effects were assessed daily by nurses for all patients; we retrospectively reviewed patient charts at the point before starting treatment with olanzapine and for three days after administration of the drug. The average grade of each symptom before and after the administration of the drug was compared. The intensity of each symptom was evaluated and classified based on the description in the patient charts and translated retrospectively as four scales (scores) as follows: none (0), mild (1), moderate (2), and severe (3). The frequency of vomiting also was noted from the medical records.
Statistical Analysis
The results are expressed as mean SD. The differences between groups were analyzed by the Wilcoxon-signed rank test.
Results During the study period, 338 patients were admitted to the palliative care unit of our hospital; of these, 20 patients met our inclusion criteria. The group comprised 13 women and seven men, with an average age of 64.7 14.9 years (range 35e90 years). Patients were diagnosed with incomplete bowel obstruction in the upper (n ¼ 11) and lower (n ¼ 9) intestines. Primary tumor sites included the
606
Kaneishi et al.
stomach (n ¼ 4), colon/rectum (n ¼ 4), uterus/ovary (n ¼ 3), lung (n ¼ 2), bile duct (n ¼ 2), urinary tract (n ¼ 2), esophagus (n ¼ 1), pancreas (n ¼ 1), and peritoneum (n ¼ 1). The average dose of olanzapine was 4.9 1.2 mg (median 5.0; range 2.5e7.5), and the average treatment duration was 23.4 16.2 days (median 21; range 2e60). During the same period, a steroid (betamethasone) had been administered before olanzapine treatment to 12 patients; the average dose of betamethasone was 3.5 2.1 mg (median 3.0; range 0.5e8), and no other antiemetic drugs were used. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4 0.7 to 0.2 0.4 (P < 0.001). The percentage of patients with none or mild nausea was 10% before olanzapine treatment; 100% of the patients experienced no or mild nausea after the treatment (Table 1). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea; no patient experienced worsening of the symptom. The average frequency of vomiting significantly decreased with olanzapine treatment from 1.1 1.3 times/day (median 0.5; range 0e4) before the treatment to 0.3 0.5 times/day (median 0; range 0e1) after the treatment (P < 0.01). Before the treatment, 10 patients experienced vomiting; eight (80%) of these patients experienced a decrease in the frequency of vomiting after the treatment. Adverse effects of olanzapine treatment included drowsiness (n ¼ 2) and dizziness (n ¼ 1). However, none of these patients chose Table 1 Change in Intensity of Nausea and Frequency of Vomiting With Olanzapine Treatments Nausea None Mild Moderate Severe Vomiting (per day) 0 1 2 3 4
Before
After
0 2 9 9
16 4 0 0
10 3 4 2 1
14 6 0 0 0
Vol. 44 No. 4 October 2012
to stop the antiemetic olanzapine treatment for these reasons. These symptoms were treated as clinical or diagnostic observations only, and the need for intervention was not indicated in any of these patients.
Discussion This study is, to our best knowledge, the first study to investigate the antiemetic activity of olanzapine in patients with inoperable and incomplete bowel obstruction. Our findings revealed that olanzapine successfully reduced the intensity of nausea and the frequency of vomiting caused by incomplete bowel obstruction. Olanzapine has been reported to be efficacious against nausea and vomiting associated with delayed emesis after chemotherapy8,11 in patients with advanced cancer.9,10 A previous study demonstrated a 39.2% improvement in chemotherapy-induced nausea by the addition of olanzapine treatment.11 Nausea relief in bowel obstruction after steroid therapy has been reported in approximately 68% of patients vs. 33% of placebo-treated patients.12 Our results were thus comparable in the effectiveness of olanzapine as an antiemetic. The other important finding of this study was that the drug was administered without any serious adverse events. Other studies also have reported that in patients with advanced cancer, olanzapine can be used with relatively few side effects9,10 and fewer drug interactions as compared with other neuroleptic agents.6 It is partly because olanzapine has five times the affinity for 5-HT2 receptors than for D2 receptors, resulting in fewer extrapyramidal side effects. However, insulin-resistant diabetes and neuroleptic malignant syndrome, although rarely reported, are possible consequences of olanzapine treatment.13 Antiemetics can be administered by various routes; medication can be tailored to each patient with regard to both compliance and the route of administration. Olanzapine (ZydisÒ) is available as an orally disintegrating disk, which can be easily administered, even to patients with nausea and vomiting. Our study had certain limitations, including the inherent limitations of a retrospective study. Furthermore, it was a single-center study with a small sample size; it lacked a control group. It
Vol. 44 No. 4 October 2012
Olanzapine for Nausea in Bowel Obstruction
is possible that the relief of nausea and vomiting might have occurred as a part of the natural course of the disease or as the result of a placebo effect in a certain percentage of patients. Generally, causes of nausea and vomiting in patients with advanced cancer are multifactorial; factors other than incomplete bowel obstruction might have partially affected these symptoms. Next, the possibility of differences in the evaluation of nausea and vomiting cannot be ruled out. Patients may have underreported the symptoms because of potential recall bias, and physicians and nurses may have failed to document them for multiple reasons, especially because no structured tools or protocols were used during record keeping. Thus, we realize that our results are clearly tentative; nonetheless, we consider that the high percentage of patients who experienced symptomatic relief (90%) demonstrates the potential of olanzapine as an effective antiemetic in cancer patients with incomplete bowel obstruction. In conclusion, our results suggest the potential efficacy of olanzapine for nausea relief in incomplete bowel obstruction. Further prospective trials, including randomized controlled trials with a placebo-controlled design and comparison with an established antiemetic, are required for validating these results.
Disclosures and Acknowledgments No funding was received for this study, and the authors declare no conflicts of interest.
References 1. Ripamonti C, Twycross R, Baines M, et al. Clinical practice recommendations for the management of bowel obstruction in patients with endestage cancer. Support Care Cancer 2001;9:223e233. 2. Davis MP, Hallerberg G. A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage 2010;39:756e767.
607
3. Fainsinger RL, Spachynski K, Hanson J, Breura E. Symptom control in terminally ill patients with malignant bowel obstruction (MBO). J Pain Symptom Manage 1994;9:12e18. 4. Baines M, Oliver DJ, Carter RL. Medical management of intestinal obstruction in patients with advanced malignant disease. A clinical and pathological study. Lancet 1985;2:990e993. 5. Tonini M, Cipollina L, Poluzzi E, et al. Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 2004;19:379e390. 6. Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 1999;37: 177e193. 7. Davis MP, Khawam E, Pozuelo L, Lagman R. Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project. Expert Rev Anticancer Ther 2002;2:365e376. 8. Passik SD, Kirsh KL, Theobald DE, et al. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Symptom Manage 2003;25:485e488. 9. Passik SD, Lundberg J, Kirsh KL, et al. A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 2002;23:526e532. 10. Srivastava M, BritoeDellan N, Davis MP, Leach M, Lagman R. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 2003;25:578e582. 11. Tan L, Liu J, Liu X, et al. Clinical research of olanzapine for prevention of chemotherapye induced nausea and vomiting. J Exp Clin Cancer Res 2009;28:131. 12. Laval G, Girardier J, Lassauni ere JM, et al. The use of steroids in the management of inoperable intestinal obstruction in terminal cancer patients: do they remove the obstruction? Palliat Med 2000;14: 3e10. 13. Ishigooka J, Murasaki M, Miura S. The olanzapine earlyephase II study group. Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia: results of an openelabel multicenter study in Japan. Psychiatry Clin Neurosci 2001;55:353e363.