The anti-psychotic drug olanzapine improves the control of breakthrough nausea and vomiting in patients receiving highly emetogenic chemotherapy, according to results of a Phase III trial reported at the ASCO Annual Meeting.
“This is the first study to demonstrate an effective treatment for breakthrough chemotherapy-induced nausea and vomiting [CINV],” said lead author Rudolph M. Navari, MD, PhD, Professor of Medicine, Associate Dean, and Clinical Director of Harper Cancer Institute at Indiana University School of Medicine-South Bend, who presented the findings at a webcast briefing held in advance of the meeting. He noted that this is the first time that breakthrough CINV has been studied in a systematic way.
In the study (Abstract 9064), 205 patients with a range of tumor types who had not previously received chemotherapy were given standard guideline-recommended drugs to prevent CINV prior to starting highly emetogenic chemotherapy with cisplatin or cyclophosphamide and doxorubicin.
Eighty of the patients developed breakthrough CINV and were randomized in a double-blind manner to receive either olanzapine (10 mg daily for three days) or metoclopramide (10 milligrams three times a day for three days).
Baseline characteristics, including age range (39 to 79 years), percentage of females (about one-fifth), ECOG performance scores (about 31% had scores of 0), and distribution of tumor types (breast, lung, lymphoma, and bladder), were similar between the two groups.
The researchers chose to test olanzapine because physicians treating patients with psychosis made the “empirical observation that they appeared to have less nausea and vomiting from other drugs they were on,” Navari said.
He added that the mechanism of action is unclear, but olanzapine appears to block receptors in the central nervous system that stimulate nausea and vomiting. Metoclopramide, which is approved to treat heartburn caused by gastroesophageal reflux, was chosen as the control drug since it has been shown to be an effective antiemetic in some circumstances, he explained, noting, though, that it is not recommended for prophylaxis in any national guidelines.
Olanzapine Outperforms Metoclopramide
Patients were monitored for 72 hours after initiation of randomization. Among the 42 patients given olanzapine, 30 (71%) had no emesis episodes, compared with 12 (32%) of the 38 patients given metoclopramide.
In addition, 28 patients (67%) in the olanzapine group reported no nausea versus nine (24%) in the metoclopramide arm. Both differences were statistically significant.
Used as an anti-psychotic, olanzapine is associated with side effects, including weight gain, although this occurs in patients after several months of treatment—“three, six, nine months”—Navari said. Used for a short period of three days as an anti-emetic in the current study, the drug was well tolerated, with no Grade 3 or Grade 4 toxicities and no central nervous system adverse effects.
Commenting on the study, ASCO 2012–2013 President Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at Medstar Washington Hospital Center, Professor of Medicine at Georgetown University, and a member of Lombardi Comprehensive Cancer Center, called the results truly remarkable—“a huge benefit for a really important quality-of-life issue.”
About 30% of patients treated with highly emetic chemotherapy will have breakthrough vomiting despite preventive treatment recommended by ASCO or other guidelines, “and [the proportion] goes up another 20 percent if you add in nausea,” she said.
“As we get better at treating and curing cancer, [these figures] remind us that we still have to find ways to improve the patient's experience.”