Granisetron HCl Tablets prevent nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, as shown by 24-hour efficacy data from studies using both moderately- and highly-emetogenic chemotherapy.
Moderately Emetogenic Chemotherapy
The first trial compared Granisetron HCl tablets doses of 0.25 mg to 2 mg bid, in 930 cancer patients receiving, principally, cyclophosphamide, carboplatin, and cisplatin (20 mg/m
2 to 50 mg/m
2). Efficacy was based on complete response (ie, no vomiting, no moderate or severe nausea, no rescue medication), no vomiting, and no nausea.
Table 2 summarizes the results of this study.
Table 2 Prevention of Nausea and Vomiting 24 Hours Post-ChemotherapyChemotherapy included oral and injectable cyclophosphamide, carboplatin, cisplatin (20 mg/m2 to 50 mg/m2), dacarbazine, doxorubicin, epirubicin.
|
Percentages of Patients
Granisetron HCl Tablet Dose |
Efficacy Measures
| 0.25 mg bid
(n=229)
%
| 0.5 mg bid
(n=235)
%
| 1 mg bid
(n=233)
%
| 2 mg bid
(n=233)
%
|
| Complete Response No vomiting, no moderate or severe nausea, no rescue medication.
| 61
| 70 Statistically significant (P<0.01) vs. 0.25 mg bid.
| 81 Statistically significant (P<0.01) vs. 0.5 mg bid.
| 72
|
No Vomiting
| 66
| 77
| 88
| 79
|
No Nausea
| 48
| 57
| 63
| 54
|
Results from a second double-blind, randomized trial evaluating Granisetron HCl Tablets 2 mg qd and Granisetron HCl Tablets 1 mg bid were compared to prochlorperazine 10 mg bid derived from a historical control. At 24 hours, there was no statistically significant difference in efficacy between the two Granisetron HCl Tablet regimens. Both regimens were statistically superior to the prochlorperazine control regimen (see
Table 3).
Table 3 Prevention of Nausea and Vomiting 24 Hours Post-ChemotherapyModerately emetogenic chemotherapeutic agents included cisplatin (20 mg/m2 to 50 mg/m2), oral and intravenous cyclophosphamide, carboplatin, dacarbazine, doxorubicin.
| Percentages of Patients |
Efficacy Measures
| Granisetron HCl tablets
1 mg bid
(n = 354)
%
| Granisetron HCltablets
2 mg qd
(n = 343)
%
| Prochlorperazine Historical control from a previous double-blind granisetron hydrochloride trial.
10 mg bid
(n=111)
%
|
| Complete Response No vomiting, no moderate or severe nausea, no rescue medication
| 69 Statistically significant (P<0.05) vs. prochlorperazine historical control.
| 64
| 41
|
No Vomiting
| 82
| 77
| 48
|
No Nausea
| 51
| 53
| 35
|
| Total Control No vomiting, no nausea, no rescue medication.
| 51
| 50
| 33
|
Results from a Granisetron HCl Tablets 2 mg qd alone treatment arm in a third double-blind, randomized trial, were compared to prochlorperazine (PCPZ), 10 mg bid, derived from a historical control. The 24-hour results for Granisetron HCl Tablets 2 mg qd were statistically superior to PCPZ for all efficacy parameters: complete response (58%), no vomiting (79%), no nausea (51%), total control (49%). The PCPZ rates are shown in Table 3.
Over 3700 patients have received Granisetron HCl Tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens.
In patients receiving GranisetronHCl Tablets 1 mg bid for 1, 7 or 14 days, or 2 mg qd for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in
Table 4.
Other adverse events reported in clinical trials were:
Table 4 Principal Adverse Events in Clinical Trials
| Percent of Patients With Event
|
| Granisetron HCl Adverse events were recorded for 7 days when granisetron hydrochloride tablets were given on a single day and for up to 28 days when granisetron hydrochloride tablets were administered for 7 or 14 days. tablets
1 mg bid
(n=978)
|
Granisetron HCl
tablets
2mg qd
(n=1450) | Comparator Metoclopramide/dexamethasone; phenothiazines/dexamethasone; dexamethasone alone; prochlorperazine.
(n=599)
| Placebo
(n=185)
|
| Headache Usually mild to moderate in severity.
| 21%
| 20%
| 13%
| 12%
|
Constipation
| 18%
| 14%
| 16%
| 8%
|
Asthenia
| 14%
| 18%
| 10%
| 4%
|
Diarrhea
| 8%
| 9%
| 10%
| 4%
|
Abdominal pain
| 6%
| 4%
| 6%
| 3%
|
Dyspepsia
| 4%
| 6%
| 5%
| 4%
|
Gastrointestinal:In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24-hour efficacy assessment period.
Hepatic:In comparative trials, elevation of AST and ALT (>2 times the upper limit of normal) following the administration of granisetron hydrochloride tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%).
Cardiovascular:Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely.
Central Nervous System:Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms have been reported in a patient treated with Granisetron HCl Tablets.
Hypersensitivity:Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.
Other:Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia(9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%).
Over 5000 patients have received injectable granisetron hydrochloride in clinical trials.
Table 5gives the comparative frequencies of the five commonly reported adverse events (≥3%) in patients receiving granisetron hydrochloride Injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following granisetron hydrochloride Injection administration.
| Percent of Patients with Event
|
| Granisetron hydrochloride Adverse events were generally recorded over 7 days post- granisetron hydrochloride Injection administration Injection
40 mcg/kg
(n=1268)
| Comparator Metoclopramide/dexamethasone and phenothiazines/dexamethasone.
(n=422)
|
Headache
| 14%
| 6%
|
Asthenia
| 5%
| 6%
|
Somnolence
| 4%
| 15%
|
Diarrhea
| 4%
| 6%
|
Constipation
| 3%
| 3%
|
In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to granisetron hydrochloride, except for headache, which was clearly more frequent than in comparison groups.
