Abstract
Abstract 5196
Patients undergoing chemotherapy (CT) commonly receive repeated cycles of treatment. While chemotherapy-induced nausea and vomiting (CINV) can be a disruptive, unwanted side effect with negative consequences on patient quality of life, possible discontinuation of therapy, and associated increased health care resources, prevention of CINV in cycle 1 diminishes its potential in subsequent cycles. Therefore, optimizing antiemetic prophylaxis at initiation of CT is critical. Palonosetron (PALO), a potent 5-HT3 receptor antagonist (RA) with a distinctly different pharmacokinetic and receptor binding profile, has demonstrated improved CINV protection compared to older 5-HT3 RAs in multiple phase 3 and 4 single-CT-cycle clinical trials; however, few studies have evaluated PALO over multiple cycles of CT.
This was a prospective, multicenter, single-arm study designed to assess the efficacy and safety of single IV doses of PALO 0.25 mg in preventing CINV in chemotherapy-naïve patients with Non-Hodgkin's Lymphomas (NHL) scheduled to receive at least 2 repeated, consecutive cycles of moderately emetogenic chemotherapy (CHOP, R-CHOP or ProMACE-CytaBOM). Corticosteroids were part of the CT regimen but not administered as an antiemetic. The primary efficacy endpoint was complete response (CR: defined as no emesis and no use of rescue medication) during the overall phase (0–120 h) following CT during each cycle. Secondary endpoints included CR during the acute (0–24 h) and delayed (24–120 h) time periods, as well as evaluation of proportion of emesis-free patients and nausea severity (according to a 100 mm VAS) during all 3 time intervals. The safety profile and adverse events were also assessed.
A total of 88 patients with either B-cell (91%) or T-cell (9%) NHL received PALO for a total of 317 CT cycles (mean 3.6; median 4). The majority of patients were white (99%) males (60%) with a mean age of 59.7 yrs who received either CHOP (47%) or R-CHOP (52%). CR rates during the acute, delayed and overall phases were sustained across the 4 CT cycles (Table). High proportions of patients remained emesis-free and experienced less than significant nausea (0 to <25 mm VAS) during the 5 days post-CT throughout repeated CT cycles (Table). PALO was well tolerated over repeated cycles, with few adverse events considered possibly/probably/definitely related (TRAEs: treatment related adverse events) (8% of patients; none serious). The incidence of the typically frequent TRAEs of headache and constipation was low (1% and 2%) and there were no unexpected or relevant differences in TRAEs between cycles or in later cycles (6%, 3%, 0%, 4% cycles 1–4, respectively).
| Efficacy Endpoint . | Cycle 1 (n = 88) . | Cycle 2 (n = 82) . | Cycle 3 (n = 78) . | Cycle 4 (n = 69) . | Total Cycles (N = 317) . |
|---|---|---|---|---|---|
| CR | |||||
| (0–24 h) | 77% | 84% | 82% | 84% | 82% |
| (24-120 h) | 83% | 94% | 92% | 94% | 91% |
| (0–120 h) (primary endpoint) | 68% | 81% | 78% | 81% | 77% |
| No Emesis | |||||
| (0–24 h) | 91% | 94% | 96% | 94% | 94% |
| (2419–>120 h)> | 89% | 95% | 94% | 96% | 93% |
| (0–120 h) | 86% | 92% | 92% | 93% | 91% |
| None/No Significant Nausea | |||||
| (0-24 h) | 94% | 94% | 96% | 94% | 95% |
| (24–120 h) | 85% | 95% | 96% | 93% | 92% |
| (0–120 h) | 83% | 92% | 94% | 91% | 90% |
| Efficacy Endpoint . | Cycle 1 (n = 88) . | Cycle 2 (n = 82) . | Cycle 3 (n = 78) . | Cycle 4 (n = 69) . | Total Cycles (N = 317) . |
|---|---|---|---|---|---|
| CR | |||||
| (0–24 h) | 77% | 84% | 82% | 84% | 82% |
| (24-120 h) | 83% | 94% | 92% | 94% | 91% |
| (0–120 h) (primary endpoint) | 68% | 81% | 78% | 81% | 77% |
| No Emesis | |||||
| (0–24 h) | 91% | 94% | 96% | 94% | 94% |
| (2419–>120 h)> | 89% | 95% | 94% | 96% | 93% |
| (0–120 h) | 86% | 92% | 92% | 93% | 91% |
| None/No Significant Nausea | |||||
| (0-24 h) | 94% | 94% | 96% | 94% | 95% |
| (24–120 h) | 85% | 95% | 96% | 93% | 92% |
| (0–120 h) | 83% | 92% | 94% | 91% | 90% |
A single, fixed IV dose of palonosetron was shown to be safe and effective in preventing CINV over repeated chemotherapy cycles in patients with NHL.
Voisin:Helsinn Healthcare: Employment. Ballinari:Helsinn Healthcare: Employment.
Author notes
Asterisk with author names denotes non-ASH members.
