Efficacy and safety of triple therapy with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy for gynecological cancer: KCOG-G1003 phase II trial.
OBJECTIVE
Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)).


METHODS
Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy).


RESULTS
Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each).


CONCLUSIONS
Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.
Department of Gynecology, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan, nobuhiro.takeshima@jfcr.or.jp.
Nobuhiro
N
Takeshima
Maki
M
Matoda
Masakazu
M
Abe
Yasuyuki
Y
Hirashima
Kentaro
K
Kai
Kaei
K
Nasu
Masashi
M
Takano
Kenichi
K
Furuya
Seiya
S
Sato
Hiroaki
H
Itamochi
Hiroshi
H
Tsubamoto
Kosei
K
Hasegawa
Kiminari
K
Terao
Takeo
T
Otsuki
Keiko
K
Kuritani
Kimihiko
K
Ito
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000077608:Aprepitant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D000077924:Palonosetron; D011446:Prospective Studies; D011788:Quality of Life; D011812:Quinuclidines / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D007546:Isoquinolines; D009025:Morpholines; D011812:Quinuclidines; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone; D002945:Cisplatin