Palonosetron administered with a single-dose of dexamethasone adequately controlled nausea and vomiting associated with non-anthracycline-based (non-AC) moderately emetogenic chemotherapy (MEC) when compared with a longer duration of dexamethasone, according to results from a phase III trial.
The goal of the study was to compare the efficacy of dexamethasone on day 1 (single administration) versus dexamethasone on days 1 to 3, in combination with the second-generation 5-HT3
receptor antagonist, palonosetron, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in non-AC-based MEC. Patients were randomly assigned to either Group B, which received palonosetron (0.75 mg, IV) and dexamethasone (9.9 mg, IV) prior to chemotherapy on day 1, or to Group A, which was administered additional dexamethasone (8 mg, IV or PO) on days 2 and 3.
Hiroshi Isobe, MD, PhD, lead researcher from the Department of Medical Oncology at KKR Sapporo Medical Center in Sapporo, Japan, cited several studies supporting the use of dexamethasone for the prevention of CINV in his presentation during the plenary session of the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Oral Oncology (ISOO) meeting in Miami, Florida.
Current antiemetic guidelines recommend that dexamethasone should be administered for 3 days with palonosetron for MEC. Isobe said that this recommendation was based on data using first generation 5-HT3
-receptor antagonists (RA), and that palonosetron in combination with single dose dexamethasone has been shown to be non-inferior to palonosetron plus 3 days of dexamethasone.
The primary endpoint was a complete response (CR) in the overall period (0-120 hr) and secondary endpoints identified as the CR and complete control (CC) rates for the acute and delayed phases, and overall period, as well as adverse events (AEs).
The full analysis set included 154 patients in Group A (3 days dexamethasone) and 151 patients in Group B (1 day dexamethasone). The results showed non-inferiority of the Group B regimen, with CR observed in 63.6% of Group A patients versus 66.2% of Group B patients (P
=0.0004). Results were consistent between the acute and delayed phases, and in the overall period. When the data were compared using risk difference with 95% Wald confidence limit for CR rate, Group A was favored in patients < 55 years, and in those receiving other chemotherapy.
“This may suggest that dexamethasone might be necessary in younger patients and [in those on] carboplatin-based regimens for three days,” said Isobe.
Cumulative CR rate was also identical in both groups, and CC rate (defined as no emetic episodes, no use of rescue medication, and no greater than mild nausea) in the overall period was 61.7% and 64.9% in the respective groups. When evaluated for risk difference using the Wald confidence limit for CC rate, Group A was again favored in patients under 55 years of age and with other chemotherapies. Total control rate (defined as no emetic episodes, no rescue medication, and no nausea) was again identical in both groups (for overall period, 47.4% and 49.7%, in Groups A and B, respectively), as was no use of rescue medication rate (69.5% and 70.2%, respectively). The frequency of AEs tended to be similar in both groups, and no unexpected AEs were reported.
Isobe said, “The administration of dexamethasone on day 2 and 3 can be omitted in the prevention of CINV [in patients] receiving non-AC MEC when used with palonosetron.”
In the post-presentation discussion, the issue was raised that MEC regimens overall can be quite a heterogeneous group, and that guidelines might need to, in the future, address the necessity of day 2 and 3 dexamethasone treatment depending on the chemotherapy regimen used; also raised was the as-yet unresolved question of whether these results might represent a palonosetron-specific effect, or whether treatment with dexamethasone beyond day 1 for many of the commonly used MECs might simply not be necessary.
Isobe H, Yuki S, Furuhata T, et al. A randomized phase III trial of palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting induced by non-AC MEC: HOPE-01. MASCC/ISOO International Symposium on Supportive Care in Cancer. Miami, FL. June 26-28, 2014.
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