Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.
BACKGROUND
Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC.


METHODS
A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron).


RESULTS
Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670.0 in palonosetron cycle). Both treatments were well tolerated and safe.


CONCLUSIONS
Transdermal granisetron is a good alternative therapeutic option to palonosetron for preventing CINV after MEC.
Division of Hemato-Oncology, Department of Internal Medicine, Pusan National University Hospital Medical Research Institute, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea.
Young Mi
YM
Seol
Division of Hemato-Oncology, Department of Internal Medicine, Pusan National University Hospital Medical Research Institute, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea.
Hyo Jeong
HJ
Kim
Division of Hemato-Oncology, Department of Internal Medicine, Pusan National University Hospital Medical Research Institute, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea.
Young Jin
YJ
Choi
Division of Hemato-Oncology, Department of Internal Medicine, Kosin University Gospel Hospital, Busan, South Korea.
Eun Mi
EM
Lee
Division of Hemato-Oncology, Department of Internal Medicine, Kosin University Gospel Hospital, Busan, South Korea.
Yang Soo
YS
Kim
Division of Hemato-Oncology, Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine, Busan, South Korea.
Sung Yong
SY
Oh
Division of Hemato-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
Su Jin
SJ
Koh
Division of Hemato-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
Jin Ho
JH
Baek
Division of Hemato-Oncology, Department of Internal Medicine, Inje University Paik Hospital, Inje University College of Medicine, Busan, South Korea.
Won Sik
WS
Lee
Division of Hemato-Oncology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.
Young Don
YD
Joo
Department of Biostatistician, Pusan National University Hospital Medical Research Institute, Busan, South Korea.
Hyun Gi
HG
Lee
Department of Biostatistician, Pusan National University Hospital Medical Research Institute, Busan, South Korea.
Eun Young
EY
Yun
Division of Hemato-Oncology, Department of Internal Medicine, Pusan National University Hospital Medical Research Institute, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea. seol2100@daum.net.
Joo Seop
JS
Chung
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D017829:Granisetron / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000077924:Palonosetron; D017060:Patient Satisfaction; D011812:Quinuclidines / Q000627:therapeutic use*; D012074:Remission Induction; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D017829:Granisetron; D007546:Isoquinolines; D000077924:Palonosetron; D011812:Quinuclidines; D012702:Serotonin Antagonists
CINV; Palonosetron; Transdermal granisetron