The antipsychotic olanzapine trounced standard therapy for breakthrough chemotherapy-induced nausea and vomiting in a clinical trial that could change the way some cancer patients are treated.
In the double-blind phase III study, 30 (71%) of 42 patients, who received olanzapine (Zyprexa) had no emesis, compared with 12 (32%) of 38 patients who received metoclopramide (P less than .01) during a 72-hour observation period after highly emetic chemotherapy.
Dr. Rudolph M. Navari
In addition, 28 (67%) patients on olanzapine had no nausea, compared with 9 (24%) of those patients on metoclopramide (P less than .01), said Dr. Rudolph M. Navari, who presented the study during a press briefing in advance of the annual meeting of American Society of Clinical Oncology, June 1-5, in Chicago. Dr. Navari is the director of the Harper Cancer Institute at Indiana University in South Bend.
ASCO president-elect Dr. Sandra M. Swain, medical director of the Cancer Institute at Washington Hospital Center, called the findings "a great step forward for quality of life for our patients.
"This is a huge advance," said Dr. Swain, a breast cancer expert, who comoderated the teleconference. "We’ve come a long way to really treat and cure these patients ... these side effects can be intolerable to patients. Sometimes patients will opt out of curative treatment, and we certainly don’t want that, when we know we’ve made advances."
The researchers included chemotherapy-naive patients who received highly emetogenic chemotherapy: more than 70 mg/m2 cisplatin, or more than 50 mg/m2 doxorubicin and more than 600 mg/m2 cyclophosphamide.
Patients who developed breakthrough emesis or nausea despite guideline-directed prophylaxis were randomized to receive olanzapine or metoclopramide. Pre-chemotherapy prophylaxis included intravenous dexamethasone (12 mg), intravenous palonosetron (0.25 mg), and intravenous fosaprepitant (150 mg); post-chemotherapy prophylaxis was daily oral dexamethasone (8 mg, days 2-4).
Patients received 10 mg oral olanzapine for 3 days or 10 mg oral metoclopramide three times daily for 3 days. Patients were monitored for emesis and nausea for the 72 hours after the initiation of therapy. In addition, nausea was measured by patients on a visual analog scale (0-10), with 0 being no nausea and 10 being maximal nausea.
Patients in the two groups were similar for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, and diagnosis (5 bladder cancers, 40 breast cancers, 8 lymphomas, and 27 lung cancers).
"Both olanzapine and metoclopramide were well tolerated with no grade 3 or 4 toxicities," said Dr. Navari. No central nervous system toxicities were observed in either group.
Olanzapine is indicated for treatment of psychosis and is associated with weight gain, but the side effect should not be a problem for cancer patients.
"The side effect of weight gain occurs in patients, who receive the drug for 3 to 6 to 9 months," Dr. Ravari noted. "So using it for a short period of 3-4 days once a month – we did not see that in the current study, nor did we see that in previous studies."
Dr. Navari had previously reported that patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant (Emend) regimen (68% vs. 37%) in a phase III clinical trial. The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting, that study found (Support. Oncol. 2011;9:188-95).
ASCO presented a preview of some meeting highlights with many of the abstracts being posted online as of 6 p.m. EST at www.asco.org.
The authors reported that they have nothing to disclose.