J Gynecol Oncol.  2015 Oct;26(4):311-319. 10.3802/jgo.2015.26.4.311.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer

• Fujiwara S
• Terai Y
• Tsunetoh S
• Sasaki H
• Kanemura M
• Ohmichi M

• KMID: 2345922
• DOI: http://doi.org/10.3802/jgo.2015.26.4.311

Abstract

OBJECTIVE
There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC.
METHODS
We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant.
RESULTS
When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001).
CONCLUSION
The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Keyword

Antiemetics; Aprepitant; Granisetron; Neoplasms; Palonosetron; Serotonin 5-HT3 Receptor Antagonist

MeSH Terms

Adult
Aged
Antiemetics/*administration & dosage
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Carboplatin/administration & dosage/adverse effects
Cross-Over Studies
Diet
Drug Administration Schedule
Female
Genital Neoplasms, Female/*drug therapy
Granisetron/administration & dosage
Humans
Isoquinolines/administration & dosage
Middle Aged
Morpholines/administration & dosage
Nausea/chemically induced/*prevention & control
Paclitaxel/administration & dosage/adverse effects
Quinuclidines/administration & dosage
Serotonin 5-HT3 Receptor Antagonists
Vomiting/chemically induced/*prevention & control
Antiemetics
Carboplatin
Granisetron
Isoquinolines
Morpholines
Quinuclidines
Serotonin 5-HT3 Receptor Antagonists
Paclitaxel

Figure

• 

  Fig. 1 Study design flowchart. During the first cycle, the patients received palonosetron or granisetron with the other two drugs, aprepitant and dexamethasone. During the next cycle, patients received the other 5-HT3 antagonist.

• 

  Fig. 2 Proportion of patients achieving a complete response (CR; no emetic episodes or use of rescue therapy) according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the first and second cycles. We compared the CR rates achieved with palonosetron and granisetron administered as 5-HT3 receptor antagonists according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the first and second cycles.

• 

  Fig. 3 Changes in the level of dietary intake by grade based on the Common Terminology Criteria for Adverse Events (CTCAE) grade according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the first and second cycles. The grade of change in the level of dietary intake was determined based on the CTCAE criteria. We compared the changes obtained with palonosetron or granisetron administered as 5-HT3 receptor antagonists according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the first and second cycles.

• 

  Fig. 4 Proportion of patients achieving a complete response (CR; no emetic episodes or use of rescue therapy) according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the third cycle. Comparison of the three drugs group (addition of aprepitant) and two drugs group. We compared the CR rates between the two groups according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the third cycle. RA, reseptor antagonist.

• 

  Fig. 5 Changes in the level of dietary intake by grade based on the Common Terminology Criteria for Adverse Events (CTCAE) criteria according to the study phase (A: acute, 0-24 hours; B: delayed, 2-7 days) during the third cycle. We compared the changes in the level of dietary intake between the patients who received two drugs (without aprepitant) and three drugs during the third cycle. RA, reseptor antagonist.

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