Background: Indisetron is a serotonin (5-hydroxytryptamine type 3) receptor antagonist that also antagonizes 5-hydroxytryptamine type 4 receptors. We designed a pilot study in order to explore the optimal dosing period for indisetron during modified FOLFOX6 (mFOLFOX6). Patients and Methods: Forty-two chemotherapy-naive patients with advanced colorectal cancer scheduled to receive mFOLFOX6 were randomly assigned to either a 1- or 3-day indisetron regimen arm. The primary endpoint was complete protection from vomiting. Results: Proportions of patients with complete protection from vomiting were 85.7% [95% confidence interval (CI) 63.7–97.0] with the 3-day regimen and 81.0% (95% CI 58.1–94.6) with the 1-day regimen. Proportions of patients with complete protection from nausea were 47.6% in each arm (95% CI 25.7–70.2). No rescue therapy rates were 66.7% (95% CI 43.0–85.4) versus 57.1% (95% CI 34.0–78.2). No severe adverse events were observed in either arm. Conclusion: Both 1- and 3-day indisetron regimens were feasible for preventing nausea and vomiting induced by mFOLFOX6.

Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, Clark-Snow R, Gill DP, Groshen S, Grunberg S, Koeller JM, Morrow GR, Perez EA, Silber JH, Pfister DG: Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol 1999;17:2971–2994.
Grunberg SM, Osoba D, Hesketh PJ, Gralla RJ, Borjeson S, Rapoport BL, du Bois A, Tonato M: Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity – an update. Support Care Cancer 2005;13:80–84.
Hesketh PJ: Chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358:2482–2494.
Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006;24:2932–2947.
Ioannidis JP, Hesketh PJ, Lau J: Contribution of dexamethasone to control of chemotherapy-induced nausea and vomiting: a meta-analysis of randomized evidence. J Clin Oncol 2000;18:3409–3422.
Aapro M: Granisetron: an update on its clinical use in the management of nausea and vomiting. Oncologist 2004;9:673–686.
Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med 2005;352:476–487.
de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938–2947.
Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22:23–30.
Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229–237.
Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L: Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008;26:2006–2012.
Fujiwara T: Pharmacologic and clinical properties of indisetron hydrochloride, a new 5-HT3 receptor antagonist for treating nausea and vomiting during cancer treatment (in Japanese with English abstract). Yakuri To Chiryo (Jpn Pharmacol Ther) 2005;33:17–45.
Nemoto M, Endo T, Minami M, Yoshioka M, Ito H, Saito H: 5-Hydroxytryptamine (5-HT)-induced depolarization in isolated abdominal vagus nerves in the rat: involvement of 5-HT3 and 5-HT4 receptors. Res Commun Mol Pathol Pharmacol 2001;109:217–230.
Horikoshi K, Yokoyama T, Kishibayashi N, Ohmori K, Ishii A, Karasawa, A: Possible involvement of 5-HT4 receptors, in addition to 5-HT3 receptors, in the emesis induced by high-dose cisplatin in Suncus murinus. Jpn J Pharmacol 2001;85:70–74.
Nukariya N, Niitani H, Sakuma A, Tsuya K: Clinical efficacy and safety profile of indisetron tablets in prevention of nausea and vomiting induced by chemotherapy including cisplatin (in Japanese with English abstract). Yakuri To Chiryo (Jpn Pharmacol Ther) 2004;32:839–853.
National Cancer Institute Common Toxicity Criteria for Adverse Events (version 3.0). (accessed November 16, 2011).
The SWOG Statistical Center. (accessed January 10, 2012).
Fuse N, Doi T, Ohtsu A, Takeuchi S, Kojima T, Taku K, Tahara M, Muto M, Asaka M, Yoshida S: Feasibility of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) for Japanese patients with unresectable metastatic colorectal cancer. Jpn J Clin Oncol 2007;37:434–439.
Gralla R, Lichinitser M, Van der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003;14:1570–1577.
Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S: Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist. Cancer 2003;98:2473–2482.
Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F: Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 2005;23:2822–2830.
Hesketh PJ, Wright O, Rosati G, Russo M, Levin J, Lane S, Moiseyenko V, Dube P, Kopp M, Makhson A: Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Support Care Cancer 2012;20:1471–1478.
Geling O, Eichler HG: Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol 2005;23:1289–1294.
Aapro MS, Grunberg SM, Manikhas GM, Olivares G, Suarez T, Tjulandin SA, Bertoli LF, Yunus F, Morrica B, Lordick F, Macciocchi A: A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 2006;17:1441–1449.
Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, Inoue K, Kitagawa C, Ogura T, Mitsuhashi S: Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009;10:115–124.
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