Abstract
In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin ≥70 mg/m2). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin ≥50 mg/m2). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.
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References
Allison DB, Casey DE (2001) Antipsychotic-associated weight gain: A review of the literature. J Clin Psychiatry 62:22–31
Bymaster FP, Calligaro D, Falcone J et al (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14:87–96
Bymaster FP, Falcone JF, Bauzon D et al (2001) Potent antagonism of 5HT3 and 5HT6 receptors by olanzapine. Eur J Pharmacol 430:341–349
Cleeland C, Mendoza T et al (2000) Assessing symptom distress in cancer patients: The M.D. Anderson Symptom Inventory. Cancer 89:1634–1646
de Boer-Dennert M, de Wit R, Schmitz PI et al (1997) Patient perceptions of the side effects of chemotherapy: the influence of the 5 HT3 antagonists. Br J Cancer 76:1055–1061
Eisenberg P, Figueroa-Vadillo J, Zamora R et al (2003) Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5HT3 receptor antagonist: Results of a phase III, single dose trial versus dolasetron. Cancer 98:2473–2482
Goldstein LE, Sporn J, Brown S et al (1999) New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 40:438–443
Gralla R, Lichinitser M, Van der Vegt S et al (2003) Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized Phase II trial comparing single does of palonosetron with ondansetron. Ann Oncol 14:1570–1577
Hale AS (1997) Olanzapine Br J Hosp Med 58:443–445
Hesketh PJ, Kris MG, Grunberg SM et al (1997) Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 15:103–109
Hesketh PJ, Grunberg SM, Gralla RJ et al (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A multinational, randomized, double-blind placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study group. J Clin Oncol 21:4112–4119
Hickok JT, Roscoe JA, Morrow GR et al (2003) Nausea and emesis remain significant problems of chemotherapy despite prophylaxis with 5 Hydroxytryptamine-3 antiemetics. Cancer 97:2880–2886
Jackson WC, Tavernier L (2003) Olanzapine for intractable nausea in palliative care patients. J Palliative Med 6:251–255
Koeller JM, Aapro MS, Gralla RJ et al (2002) Antiemetic guidelines: creating a more practical treatment approach. Support Care Cancer 10:517–518
Kris MG (2003) Why do we need another antiemetic? Just ask. J Clin Oncol 21:4077–4080
Latreille J, Pater J, Johnston D et al (1998) Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. J Clin Oncol 16:1174–1178
Navari RM (2003) Pathogenesis–based treatment of chemotherapy-induced nausea and vomiting: Two new agents. J Support Oncol 1:89–103
Navari RM. (2004) Inhibiting substance P pathway for prevention of chemotherapy-induced emesis: Preclinical data, clinical trials of neurokinin-1 receptor antagonists. Supportive Cancer Therapy 1:89–96
Navari, RM, Madajcwicz S, Anderson N et al (1995) Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo. J Clin Oncol 13:2408–2416
Navari RM, Reinhardt RR, Gralla RJ et al (1999) Reduction of cisplatin-induced emesis by a selective neurokin-1 receptor antagonist. N Engl J Med 340:190–195
Osoba D, Zee B, Warr D et al (1997) Effect of post-chemotherapy nausea and vomiting on health related quality of life. Support Care Cancer 5:307–313
Passik SD, Lundberg J., Kirsh K et al (2002) A pilot exploration of the antiemetic activity of olanzapine (Zyprexa) for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 23:526–532
Passik SD, Kirsh KL, Theobald DE et al (2003) A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Symptom Manage 25:485–489
Passik S, Navari RM, Loehrer PJ et al (2004) A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients receiving chemotherapy. Cancer Invest 22:383–388
Pater JL, Lofters WS, Zee B et al (1997) The role of the 5-HT3 antagonists’ ondansetron and dolasetron in the control of delayed onset nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Ann Oncol 8:181–185
Pirl WF, Roth AJ (2000) Remission of chemotherapy-induced emesis with concurrent olanzapine treatment: A case report. Psychooncology 9:84–87
Poli-Bigelli S, Rodrigues-Pereira J, Carides AD et al (2003) Addition of the neurokinin-1 receptor antagonist Aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Cancer 97:3090–3098
Srivastava M, Brito-Dellan N, Davis MP et al (2003) Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 25:578–582
The Italian Group for Antiemetic Research (2000) Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med 342:1554–1559
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Navari, R.M., Einhorn, L.H., Passik, S.D. et al. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study. Support Care Cancer 13, 529–534 (2005). https://doi.org/10.1007/s00520-004-0755-6
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DOI: https://doi.org/10.1007/s00520-004-0755-6