Transdermal Granisetron

To compare the efficacy and tolerability of the granisetron transdermal delivery system (GTDS) to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV)

Patients were randomized to oral (2 mg per day for 3–5 days) or transdermal (one GTDS patch over 7 days) granisetron before receiving multiday chemotherapy. Patients received placebo capsules or capsules according to group assignment. Corticosteroids and rescue medications were given at the discretion of the investigator. Patients were followed for 14 days after chemotherapy.

• The study consisted of 582 participants.
• The mean age of participants in the GTDS group was 54 years (SD = 13 years). The mean age of participants in the oral granisetron group was 55 years (SD = 14 years).
• In the GTDS group, 52% of patients were female and 48% were male. In the oral granisetron group, 51% were female and 49% were male.
• Diagnoses were not provided.
• Patients were receiving the first cycle of a new multiday moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) regimen.

The study was conducted at multiple sites in Europe, the United States, Mexico, and India.

This was a randomized, double-blind, controlled trial.

Patients recorded the following in diaries daily.

• Vomiting, presence and severity, on a five-point scale ranging from 1 = none and 5 = very severe.
• Nausea, presence and severity, on a four-point scale ranging from 1 = none and 4 = severe.

Complete control (CC) was defined as no vomiting or retching, no more than mild nausea, and no use of rescue medication from the first administration until 24 hours after the last administration of chemotherapy.

• GTDS was not inferior to oral granisetron in CC.
• The percentage of patients achieving complete response (CR) or total control (TC) was not significantly different.
• Time to failure and time to treatment CC failure were similar.
• In patients receiving three- and five-day chemotherapy regimens, CC and CR were similar between the GTDS and oral granisetron groups.
• The GTDS group reported more constipation, and the oral granisetron group reported more headaches.
• In the experimental group, 65% of patients achieved CR with oral graniestron, and, in the control group, 60% of patients achieved CR with oral granisetron.

The GTDS provided effective, well-tolerated control of CINV associated with moderately or highly emetogenic, multiday chemotherapy.

• Diagnoses were not reported.
• No information was provided or subgroup analysis done on the use of dexamethasone or rescue medications.
• No differentiation or analysis was provided regarding acute versus delayed nausea or between those receiving MEC or HEC.
• No neurokinin 1 (NK1) receptor antagonists were used.

GTDS could be an option for CINV from multiday chemotherapy regimens. Further research to determine the role of this approach within an overall antiemetic regimen is warranted.

To determine the efficacy (as measured by complete response [CR]) of the granisetron transdermal system (GTS) compared to IV and oral granisetron in managing chemotherapy-induced nausea and vomiting (CINV) in Korean patients receiving moderately emetogenic chemotherapy (MEC)

Adult patients with cancer (aged 20 years or greater) assigned to receive the first cycle of a MEC regimen (according to National Comprehensive Cancer Network guidelines) in three hospitals in Korea were eligible to participate. Patients were randomly assigned to receive either GTS or IV/PO granisetron. In the GTS group, patches were applied 24–48 hours prior to chemotherapy and left in place for four days. In the control group, patients received 3 mg IV granisetron day 1 and 1 mg of oral granisetron every 12 hours on days 2 and 3. All patients received 10 mg of IV decadron on day 1. Patients recorded daily in diaries and rated nausea and vomiting on four- and five-point scales. Quality of life was assessed using the Functional Living Index-Emesis (FLI-E). The primary endpoint was the percentage of patients achieving complete response from beginning of chemotherapy until after the final administration from the PPS group.

• N = 263
• MEDIAN AGE = 56 years
• MALES: 62.4%, FEMALES: 37.6%
• KEY DISEASE CHARACTERISTICS: 97.9% had gastrointestinal cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Eastern Cooperative Oncology Group score ≤ 2; life expectancy of ≥ 3 months; receiving a three-day course of MEC; 77% receiving either FOLFOX or FOLFIRI; exclusion criteria included all other sources of nausea and vomiting including opioids for pain

• SITE: Multi-site    
• SETTING TYPE: Multiple settings  
• LOCATION: Three hospitals in South Korea

• PHASE OF CARE: Active antitumor treatment

Randomized, active controlled, open-label, prospective, multicenter trial

The primary efficacy endpoint was CR for the entire regimen, and the secondary endpoint was daily complete response. Patients kept daily diaries, and the Functional Living Index-Emesis (FLI-E) was used to measure patient satisfaction. Efficacy was assessed using a noninferiority model with a noninferiority margin of 15% as determined by a previous comparison research of serotonin antagonists.

GTS showed noninferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of the control group. GTS offers a convenient alternative option for relieving CINV in patients receiving MEC.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Findings not generalizable

Because the results of this trial suggest GTS is no-inferior to IV or oral granisetron it offers a convenient alternative for relieving CINV in patients receiving MEC. GTS should be considered for patients with gastrointestinal malignancies who are at an even greater risk of having issues with nausea, abdominal pain, or malabsorption, especially male patients.

To compare the efficacy and tolerability of the granisetron transdermal delivery system (GTDS) to palonosetron for the control of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC)

Eligible patients were randomized to either the granisetron group (GP) or palonosetron group (PG). The GP group received transdermal granisetron (one patch, seven days) for the first chemotherapy cycle and palonosetron (IV 0.25 mg/day, one day) for the second chemotherapy before receiving MEC in two consecutive cycles. The PG received palonosetron for cycle 1 and granisetron for cycle 2. Granisetron was applied 24–48 hours prior to the start of chemotherapy in both groups and left in place for seven days. IV injection of palonosetron 0.25 mg was given 30 minutes prior to chemotherapy on day 1. Both groups received dexamethasone (IV 10 mg) within 30 minutes before chemotherapy on day 1. All subjects were followed for a total of 15 days. Patient diaries were used to record the following: emetic episodes, use of rescue medications, patch adhesion, and severity of nausea (which was evaluated daily until day 4) by the CTCAE. Adverse events and vital signs were also recorded.

• N =188   
• AGE = 29–83 years
• MALES: 59.3% GP, 65% PG  
• FEMALES: 40.7% GP, 35% PG
• CURRENT TREATMENT: Chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving MEC combining 5-fluorouracil/leucovorin with Irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) in two consecutive chemotherapy cycles

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Korea

PHASE OF CARE: Active antitumor treatment

Multicenter, randomized, open-label, cross-over, active-controlled, phase IV study

• Complete response in acute and delayed phases—no emesis and no use of rescue medication
• Functional Living Index-Emesis (FLI-E)

The GTDS cycles showed noninferiority to palonosetron cycles during the acute phase. Complete responses were achieved by 75% of patients in the GTDS cycles and 80% in the palonosetron cycles. There was no significant difference in complete response rate of acute phase after the first cycle and the second cycle between the GP group and PG group (p = 0.405, p = 0.074).  Similar proportions of compete response were noted during the overall period of 0–72 hours. In both groups, small portions of patients had severe nausea during the acute phase (3 of 175 in the GTDS cycle and 1 of 175 of the palonosetron cycle). Satisfaction scores were measured by FLI-E and were equal in both groups for patients in the PG group, but in the GP group, patients' scores were lower in the palonosetron cycle versus GTDS. There were no differences in adverse events between the groups.

This study demonstrated that the granisetron transdermal delivery system is noninferior to palonosetron for relieving CINV in patients receiving MEC. Patients' satisfaction was higher with the GTDS than with palonosetron.

The GTDS is noninferior to palonosetron for patients receiving MEC. This may be a valuable option for patients who are unable to swallow pills or who have impaired absorption.

To evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately and highly emetogenic chemotherapy

• This article describes two clinical trials. The first, which was a phase II study, consisted of 210 patients with cancer. The second, which was a phase III study, consisted of 641 patients with cancer.
• Ages, gender, and key disease characteristics were not specified.

This was a multisite study conducted in the inpatient setting. The phase II trial was conducted in Germany. The phase III trial was conducted in nine countries.

All patients were in active treatment. Clinical applications of these studies are late effects and survivorship.

• The first clinical trial was a double-blind, double-dummy, randomized, multicenter study.
• The second trial was a randomized, active control, double-blind, double-dummy, parallel group, multicenter, multinational study.

In the first trial, patients used a Likert-type scale and visual analog scale (VAS) to measure CINV.

• No statistically significant differences were found in severity of nausea and vomiting, number of emetic episodes, or patient satisfaction between the two trial groups.
• Constipation was more common in patients treated with the granisetron patch compared with patients who were treated with oral granisetron.

Transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with moderate and high emetogenic potential; its efficacy and safety are fully comparable with those of oral granisetron.

Age, gender, cancer type, and stage were not mentioned.

The transdermal route may bring more comfort to patients. The patch is simple to apply and is maintained throughout chemotherapy without skin problems in most patients. The use of transdermal patch can avoid one of the many venous manipulations necessary in chemotherapy. Also, patches could be helpful in patients with swallowing problems.  Nurses need to consider obstacles, including cost and insurance coverage, when selecting antiemetics.

To compare the efficacy and tolerability of transdermal granisetron to oral granisetron

Patients were randomized to receive either a granisetron patch and placebo capsules or a placebo patch and granisetron capsules. Samples were stratified according to emetogenicity of chemotherapy, gender, and chemotherapy duration. Patches were applied for 24-48 hours before chemotherapy and left in place for seven days. Patients received 1 mg oral medication one to two hours before chemotherapy and then 1 mg every 12 hours throughout chemotherapy.

• N = 313   
• MEDIAN AGE = 59 years, 57 years
• MALES: 61%, FEMALES: 30%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Varied tumor types—lung and gastrointestinal were most common.
• OTHER KEY SAMPLE CHARACTERISTICS: About one-third were chemotherapy naive.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: China

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, parallel group trial

• Complete control (CC): no vomiting or retching, no rescue medication, and no more than mild nausea
• Time to failure of CC
• Complete response (CR): no vomiting or retching, no use of rescue medication

More patients in the oral granisetron group achieved CC (58.97% versus 46.75%, p = 0.04). The biggest difference occurred on the first day of chemotherapy. From days 2–5, no significant difference existed between groups. There were no differences based on gender, age, or emetogenicity of the chemotherapy regimen. More patients taking oral granisetron reported constipation.

In this study, oral granisetron was more effective than transdermal granisetron for control of chemotherapy-induced nausea and vomiting (CINV) during the acute phase.

• Measurement/methods not well described
• Documentation of CINV episodes was not described.
• Other antiemetics recommended for highly and moderately emetogenic chemotherapy were not used.

In this study, oral granisetron was more effective for CINV prevention than transdermal granisetron during the acute phase. In the delayed phase, results were similar for both interventions. It is unclear if the timing of application of the transdermal medication may affect this finding.