medwireNews: Adding olanzapine 5 mg to standard aprepitant, palonosetron, and dexamethasone antiemetic therapy significantly reduces the number of patients vomiting and needing rescue medication following cisplatin-based chemotherapy, Japanese researchers report.
Masakazu Abe (Shizuoka Cancer Center, Nagaizumi) and co-investigators say: “The present four-drug combination therapy containing olanzapine 5 mg sufficiently controls nausea and vomiting at a lower dose compared with the olanzapine 10 mg recommended by several guidelines,” and could therefore “be a new standard antiemetic therapy for patients undergoing cisplatin-based chemotherapy.”
The J-FORCE study included 705 patients aged 20–75 years with a malignant solid tumor (around half had lung cancer) who were due to undergo their first treatment with cisplatin (≥50 mg/m2) at 26 hospitals in Japan.
The participants were randomly assigned to receive either oral olanzapine 5 mg (n=354) or placebo (n=351) once daily on days 1–4 combined with aprepitant, palonosetron, and dexamethasone at standard doses used for antiemetic therapy against highly emetogenic chemotherapy.
As reported in The Lancet Oncology, significantly more patients in the olanzapine than in the placebo group achieved a complete response, defined as absence of vomiting and no use of rescue medications in the delayed 24–120-hour postchemotherapy period, at 79% versus 66%.
Abe and co-authors comment that not only is this difference statistically significant, it is also “clinically relevant” because “it exceeded the minimum difference of 10% for most efficacy assessments.”
The complete response rates were also significantly higher with olanzapine versus placebo in the acute phase (0–24 hours; 95 vs 89%) and in the overall period (0–120 hours; 78 vs 64%).
Similarly, patients receiving olanzapine had significantly higher rates of total control – defined as no reported nausea – in the delayed (60 vs 50%) and overall (59 vs 48%) periods.
Somnolence has been reported as a concern with the 10 mg dose of olanzapine, say the investigators, but in the current study, the proportion of patients who graded their severity of daytime sleepiness as “very much” was only significantly higher with olanzapine than with placebo on day 1. The two groups reported similar levels of sleepiness thereafter.
The researchers suggest that the reduction in sleepiness compared with previous studies “might be linked to the lower olanzapine dose” as well as the fact that it was administered after the evening meal meaning that “the concentration of olanzapine in the blood reaches its peak while patients are sleeping.”
There were only two grade 3 treatment-related adverse events during the study, one case of constipation and one of somnolence, both in the olanzapine group.
In an accompanying comment, Alex Molassiotis, from The Hong Kong Polytechnic University, says that although the trial was “very well designed and executed” its limitations include a lack of comparison with 10 mg olanzapine and the fact that all participants were Japanese and recruited from a single healthcare system, which may limit generalizability of the findings.
Nonetheless, Molassiotis believes that such limitations do not “call the results into question.”
He therefore concludes: “We have mounting evidence that olanzapine is a useful addition to antiemetic regimens. The question of dose, which is the pertinent issue, is sufficiently answered by this trial, alongside other smaller studies and phase 2 trials.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30678-3
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30791-0