Adults
In a double-blind trial of three different dosing regimens of Ondansetron Injection, 0.015 mg/kg, 0.15 mg/kg, and 0.30 mg/kg, each given three times during the course of cancer chemotherapy, the 0.15 mg/kg dosing regimen was more effective than the 0.015 mg/kg dosing regimen. The 0.30 mg/kg dosing regimen was not shown to be more effective than the 0.15 mg/kg dosing regimen.
Cisplatin-Based Chemotherapy: In a double-blind trial in 28 patients, Ondansetron Injection (three 0.15 mg/kg doses) was significantly more effective than placebo in preventing nausea and vomiting induced by cisplatin-based chemotherapy. Therapeutic response was as shown in Table 7.
Table 7. Therapeutic Response in Prevention of Chemotherapy-Induced Nausea and Vomiting in Single-day Cisplatin Therapy* in Adults | Ondansetron Injection (0.15 mg/kg × 3) | Placebo | P-value† |
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Number of patients | 14 | 14 | |
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|
Treatment response | | | |
0 Emetic episodes | 2 (14%) | 0 (0%) | |
1–2 Emetic episodes | 8 (57%) | 0 (0%) | |
3–5 Emetic episodes | 2 (14%) | 1 (7%) | |
More than 5 emetic episodes/rescued | 2 (14%) | 13 (93%) | 0.001 |
Median number of emetic episodes | 1.5 | Undefined‡ | |
Median time to first emetic episode (h) | 11.6 | 2.8 | 0.001 |
Median nausea scores (0–100)§ | 3 | 59 | 0.034 |
Global satisfaction with control of nausea and vomiting (0–100)¶ | 96 | 10.5 | 0.009 |
Ondansetron injection (0.15 mg/kg × 3 doses) was compared with metoclopramide (2 mg/kg × 6 doses) in a single-blind trial in 307 patients receiving cisplatin ≥ 100 mg/m2 with or without other chemotherapeutic agents. Patients received the first dose of ondansetron or metoclopramide 30 minutes before cisplatin. Two additional ondansetron doses were administered 4 and 8 hours later, or five additional metoclopramide doses were administered 2, 4, 7, 10, and 13 hours later. Cisplatin was administered over a period of 3 hours or less. Episodes of vomiting and retching were tabulated over the period of 24 hours after cisplatin. The results of this trial are summarized in Table 8.
Table 8. Therapeutic Response in Prevention of Vomiting Induced by Cisplatin (≥ 100 mg/m2) Single-day Therapy* in Adults | Ondansetron Injection 0.15 mg/kg × 3 | Metoclopramide 2 mg/kg × 6 | P-value |
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|
Number of patients in efficacy population | 136 | 138 | |
Treatment response | | | |
0 Emetic episodes | 54 (40%) | 41 (30%) | |
1–2 Emetic episodes | 34 (25%) | 30 (22%) | |
3–5 Emetic episodes | 19 (14%) | 18 (13%) | |
More than 5 emetic episodes/rescued | 29 (21%) | 49 (36%) | |
Comparison of treatments with respect to | | | |
0 Emetic episodes | 54/136 | 41/138 | 0.083 |
More than 5 emetic episodes/rescued | 29/136 | 49/138 | 0.009 |
Median number of emetic episodes | 1 | 2 | 0.005 |
Median time to first emetic episode (h) | 20.5 | 4.3 | < 0.001 |
Global satisfaction with control of nausea and vomiting (0–100)† | 85 | 63 | 0.001 |
Acute dystonic reactions | 0 | 8 | 0.005 |
Akathisia | 0 | 10 | 0.002 |
Cyclophosphamide-Based Chemotherapy: In a double-blind, placebo-controlled trial of Ondansetron Injection (three 0.15 mg/kg doses) in 20 patients receiving cyclophosphamide (500 to 600 mg/m2) chemotherapy, Ondansetron Injection was significantly more effective than placebo in preventing nausea and vomiting. The results are summarized in Table 9.
Table 9. Therapeutic Response in Prevention of Chemotherapy-Induced Nausea and Vomiting in Single-day Cyclophosphamide Therapy* in Adults | Ondansetron Injection (0.15 mg/kg × 3) | Placebo | P-value† |
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|
Number of patients | 10 | 10 | |
Treatment response | | | |
0 Emetic episodes | 7 (70%) | 0 (0%) | 0.001 |
1–2 Emetic episodes | 0 (0%) | 2 (20%) | |
3–5 Emetic episodes | 2 (20%) | 4 (40%) | |
More than 5 emetic episodes/rescued | 1 (10%) | 4 (40%) | 0.131 |
Median number of emetic episodes | 0 | 4 | 0.008 |
Median time to first emetic episode (h) | Undefined‡ | 8.79 | |
Median nausea scores (0–100)§ | 0 | 60 | 0.001 |
Global satisfaction with control of nausea and vomiting (0–100)¶ | 100 | 52 | 0.008 |
Re-treatment: In uncontrolled trials, 127 patients receiving cisplatin (median dose, 100 mg/m2) and ondansetron who had two or fewer emetic episodes were re-treated with ondansetron and chemotherapy, mainly cisplatin, for a total of 269 re-treatment courses (median: 2; range, 1 to 10). No emetic episodes occurred in 160 (59%), and two or fewer emetic episodes occurred in 217 (81%) re-treatment courses.
Pediatrics
Four open-label, noncomparative (one US, three foreign) trials have been performed with 209 pediatric cancer patients aged 4 to 18 years given a variety of cisplatin or noncisplatin regimens. In the three foreign trials, the initial dose of Ondansetron Injection ranged from 0.04 to 0.87 mg/kg for a total dose of 2.16 to 12 mg. This was followed by the oral administration of ondansetron ranging from 4 to 24 mg daily for 3 days. In the US trial, ondansetron was administered intravenously (only) in three doses of 0.15 mg/kg each for a total daily dose of 7.2 to 39 mg. In these trials, 58% of the 196 evaluable patients had a complete response (no emetic episodes) on Day 1. Thus, prevention of vomiting in these pediatric patients was essentially the same as for patients older than 18 years.
An open-label, multicenter, noncomparative trial has been performed in 75 pediatric cancer patients aged 6 to 48 months receiving at least one moderately or highly emetogenic chemotherapeutic agent. Fifty-seven percent (57%) were females; 67% were white, 18% were American Hispanic, and 15% were black patients. Ondansetron was administered intravenously over 15 minutes in three doses of 0.15 mg/kg. The first dose was administered 30 minutes before the start of chemotherapy; the second and third doses were administered 4 and 8 hours after the first dose, respectively. Eighteen patients (25%) received routine prophylactic dexamethasone (i.e., not given as rescue). Of the 75 evaluable patients, 56% had a complete response (no emetic episodes) on Day 1. Thus, prevention of vomiting in these pediatric patients was comparable to the prevention of vomiting in patients aged 4 years and older.