Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

Nygren, Peter; Hande, Kenneth R.; Petty, Kevin J.; Fedgchin, Maggie; Dyck, Kristien Van; Majumdar, Anup; Panebianco, D.; Smet, M. De; Ahmed, Tuli; Murphy, M. Gail; Gottesdiener, Keith; Cocquyt, Véronique; Belle, Simon Van

doi:10.1007/s00280-004-0946-3

Cited by 59 publications

(25 citation statements)

References 15 publications

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“…Since aprepitant has an inhibitory effect on CYP3A4, interactions between aprepitant and antitumor agents metabolized by CYP3A4 were a concern. Supporting overseas reports that failed to find notable interactions between aprepitant and docetaxel or vinorelbine, (17,18) the present study showed that the incidence of adverse events was not affected by combining aprepitant with antitumor agents metabolized by CYP3A4. These results showed that the safety of aprepitant is maintained irrespective of which metabolic pathways are disrupted by the antitumor agents.…”

Section: Discussionsupporting

confidence: 79%

Multicenter, phase II, placebo‐controlled, double‐blind, randomized study of aprepitant in Japanese patients receiving high‐dose cisplatin

et al. 2010

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Aprepitant is a new neurokinin-1 (NK 1 ) receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). To evaluate the efficacy and safety of aprepitant used in combination with standard therapy (granisetron and dexamethasone), we conducted a multicenter, phase II, placebo-controlled, double-blind, randomized study in Japanese cancer patients who received cancer chemotherapy including cisplatin ( ‡70 mg ⁄ m 2 ). Aprepitant was administered for 5 days. A total of 453 patients were enrolled. In the three study groups, (i) standard therapy, (ii) aprepitant 40 ⁄ 25 mg (40 mg on day 1 and 25 mg on days 2-5) and (iii) aprepitant 125 ⁄ 80 mg (125 mg on day 1 and 80 mg on days 2-5), the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (75 ⁄ 149 subjects), 66.4% (95 ⁄ 143 subjects) and 70.5% (103 ⁄ 146 subjects), respectively. This shows that efficacy was significantly higher in the aprepitant 40 ⁄ 25 mg and 125 ⁄ 80 mg groups than in the standard therapy group (v 2 test [closed testing procedure]: P = 0.0053 and P = 0.0004, respectively) and highest in the aprepitant 125 ⁄ 80 mg group. The delayed phase efficacy (days 2-5) was similar to the overall phase efficacy (days 1-5), indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. In terms of safety, aprepitant was generally well tolerated in Japanese cancer patients. (ClinicalTrials.gov number, NCT00212602.) (Cancer Sci 2010; 101: 2455-2461 C hemotherapy-induced nausea and vomiting (CINV) is a common adverse event observed in more than 90% of patients treated with highly emetogenic antitumor agents, especially cisplatin.(1,2)In general, CINV persists for approximately 5 days.(3) The CINV that occurs within 24 h after administration of antitumor agents is defined as acute phase CINV, and delayed phase CINV occurs 2-5 days after administration of antitumor agents. It has been reported that the incidence of nausea ⁄ vomiting induced by cisplatin, the most highly emetogenic antitumor agent, is 98% in the acute phase and 77% in the delayed phase after administration of 50 mg ⁄ m 2 or higher doses without preventive treatment. (4) As of October 2009 in Japan, the standard antiemetic therapy for CINV is a 5-HT 3 receptor antagonist plus dexamethasone. In the presence of this therapy, CINV is known to occur in approximately 25 and 50% of patients treated with highly emetogenic antitumor agents in the acute and delayed phases, respectively.(5) In addition, the percentage of patients who developed CINV under standard antiemetic therapy increased from approximately 50% in the first course of cancer chemotherapy to approximately 75% in the sixth course. (6,7) In several clinical studies of a 5-HT 3 receptor antagonist with dexamethasone, no efficacy was demonstrated for CINV in the delayed phase. (3,8) Aprepitant is a neurokinin-1 (NK 1 ) receptor antagonist developed as a treatment for CINV. It acts by inhibiting the binding of substance P to the NK 1 rec...

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Section: Discussionsupporting

confidence: 79%

Multicenter, phase II, placebo‐controlled, double‐blind, randomized study of aprepitant in Japanese patients receiving high‐dose cisplatin

et al. 2010

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“…As such, a potential risk of interaction with cytotoxic drugs metabolized by CYP3A4 may occur. However, in a study by Nygren et al, aprepitant had no clinically significant effect on either the pharmacokinetics or the toxicity of standard doses of docetaxel in cancer patients [25]. The authors concluded that aprepitant given at clinically recommended doses may only have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.…”

Section: Side Effectsmentioning

confidence: 95%

Neurokinin-1-Receptor Antagonists: A New Approach in Antiemetic Therapy

Jordan

2006

Oncol Res Treat

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Aprepitant (Emend®), the first neurokinin-1-receptor antagonist (NK-1-RA), represents a new class of antiemetics. Aprepitant has been approved for the prevention and treatment of acute (0-24 h after chemotherapy) and delayed (1-5 days after chemotherapy) emesis resulting from cisplatin-based chemotherapy and moderately emetogenic chemotherapy. The addition of aprepitant to standard antiemetic therapy in cisplatin-based chemotherapy significantly improves emesis protection in general and, in particular, in the delayed phase by approximately 20%. Results from a recently published study in patients receiving moderately emetogenic chemotherapy suggest a benefit of aprepitant when combined with dexamethasone and a 5-HT3 receptor antagonist for the prevention of acute emesis, followed by aprepitant as a single agent in the prevention of delayed emesis. Altogether, the addition of aprepitant to the standard antiemetic regimen (5-HT3 receptor antagonist and dexamethasone) significantly improves the protection against vomiting in the acute as well as in the delayed phase in highly and moderately emetogenic chemotherapies. Therefore, the combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant should be considered as a new standard antiemetic therapy.

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“…Theoretical concerns that aprepitant might interact with chemotherapeutic agents could not be demonstrated in preclinical and clinical studies so far [23].…”

Section: Nk 1 Ras Aprepitantmentioning

confidence: 99%

Guidelines for Antiemetic Treatment of Chemotherapy-Induced Nausea and Vomiting: Past, Present, and Future Recommendations

2007

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After completing this course, the reader will be able to:1. Explain the optimal antiemetic prophylaxis for patients receiving chemotherapy in regard to the emetogenic potential of the therapy.2. Describe the difference between acute and delayed emesis.3. Discuss the properties and optimal use of the different antiemetic drugs.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT

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Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

Cited by 59 publications

References 15 publications

Multicenter, phase II, placebo‐controlled, double‐blind, randomized study of aprepitant in Japanese patients receiving high‐dose cisplatin

Multicenter, phase II, placebo‐controlled, double‐blind, randomized study of aprepitant in Japanese patients receiving high‐dose cisplatin

Neurokinin-1-Receptor Antagonists: A New Approach in Antiemetic Therapy

Guidelines for Antiemetic Treatment of Chemotherapy-Induced Nausea and Vomiting: Past, Present, and Future Recommendations

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