Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

Abstract

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

• Authors: Yoshito Komatsu, Kenji Okita, Satoshi Yuki, Tomohisa Furuhata, Hiraku Fukushima, Hiroyuki Masuko, Yasuyuki Kawamoto, Hiroshi Isobe, Takuto Miyagishima, Kazuaki Sasaki, Michio Nakamura, Yoshinobu Ohsaki, Junta Nakajima, Miki Tateyama, Kazunori Eto, Shinya Minami, Ryoji Yokoyama, Ichiro Iwanaga, Hitoshi Shibuya, Mineo Kudo, Koji Oba, Yasuo Takahashi
• Journal: Cancer science (Cancer Sci) Vol. 106 Issue 7 Pg. 891-5 (Jul 2015) ISSN: 1349-7006 [Electronic] England
• PMID: 25872578 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antiemetics
• Isoquinolines
• Organoplatinum Compounds
• Quinuclidines
• Serotonin Antagonists
• Oxaliplatin
• Palonosetron
• Irinotecan
• Dexamethasone
• Camptothecin

Topics

• Antiemetics (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Dexamethasone (administration & dosage)
• Female
• Humans
• Irinotecan
• Isoquinolines (therapeutic use)
• Male
• Middle Aged
• Nausea (chemically induced, drug therapy)
• Neoplasms (drug therapy)
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Palonosetron
• Quality of Life
• Quinuclidines (therapeutic use)
• Serotonin Antagonists (therapeutic use)
• Treatment Outcome