Acta Oto-Laryngologica. 2014; 134: 1198–1204

ORIGINAL ARTICLE

Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas KIYOAKI TSUKAHARA1, KAZUHIRO NAKAMURA1, RAY MOTOHASHI1, HIROKI SATO1, MINORU ENDO1, YASUAKI KATSUBE1, YURI UEDA1 & MAMORU SUZUKI2 1

Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo and Department of Otolaryngology, Tokyo Medical University, Tokyo, Japan

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Abstract Conclusion: Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma. Objective: A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines. Methods: Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition. Results: The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.

Keywords: Chemotherapy-induced nausea and vomiting, CINV, aprepitant, rescue therapy, food intake

Introduction Platinum-containing drugs are the major agents used in head and neck carcinoma chemotherapy. However, platinum-containing agents, particularly cisplatin (CDDP), cause severe chemotherapy-induced nausea and vomiting (CINV) [1], an adverse effect that causes tremendous distress to patients. For this reason, the guidelines of the American Society of Clinical Oncology (ASCO), Multinational Association of Supportive Care in Cancer (MASCC), and National Comprehensive Cancer Network (NCCN) [2–4] all recommend concomitant administration of three agents as standard antiemetic therapy with CDDP: a 5-hydroxytryptamine receptor antagonist

(5-HT3RA), to inhibit serotonin peripherally in the acute phase; a neurokinin-1 receptor antagonist (NK1RA), to inhibit substance P centrally in the acute and delayed phases; and dexamethasone. The NK1 receptor antagonist aprepitant has been reported to have good antiemetic activity [5]. However, in patients with head and neck carcinoma, structural disorders due to the carcinoma and radiation mucositis-induced pain make the ingestion of an oral agent like aprepitant difficult. Also, aprepitant has to be taken for 3 days, causing concern about reduced compliance in chemotherapy outpatients. As a solution to these problems, fosaprepitant, a pro-drug of aprepitant administered on only a single day, was developed. Fosaprepitant is reportedly not inferior

Correspondence: Kiyoaki Tsukahara, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan. Tel: +81 42 665 5611. Fax: +81 42 665 5639. E-mail: [email protected]

(Received 2 March 2014; accepted 22 March 2014) ISSN 0001-6489 print/ISSN 1651-2251 online  2014 Informa Healthcare DOI: 10.3109/00016489.2014.913314

Antiemetic therapy of fosaprepitant to aprepitant according to clinical trials conducted mainly on patients with lung cancer and digestive carcinoma [6]. However, no studies have clarified the efficacy of fosaprepitant when used as the NK1RA for CDDP-based chemotherapy in head and neck carcinomas. The purpose of the present study was to evaluate the effectiveness of concomitant administration of fosaprepitant as the NK1RA, palonosetron as the 5-HT3RA, and dexamethasone with CDDP-based chemotherapy in patients with head and neck carcinoma.

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given at 2 Gy/day; when 40 Gy had been reached, a 14-day split was introduced. Taking the day of starting radiotherapy as day 1, DOC was administered at 50 mg/m2 on days 1 and 42, CDDP at 60 mg/m2 on days 4 and 45, and 5-FU at 600 mg/m2 on days 1– 4 and 42–45. In postoperative therapy, radiotherapy was given at 2 Gy/day for a total dose of 50–60 Gy. Taking the start of radiotherapy as day 1, CDDP was administered at 80 mg/m2 on days 1 and 36 (Figure 1). Fosaprepitant was administered at 150 mg/kg body weight, palonosetron at 0.75 mg/kg body weight, and dexamethasone at 10 mg/kg body weight on the same day as CDDP. Furthermore, over the period of chemotherapy or until day 3 of CDDP, dexamethasone was administered at 6.6 mg/kg body weight. When nausea or vomiting that could not be tolerated by patients occurred, rescue therapy (i.e. metoclopramide, domperidone, or lorazepam) was administered. CINV persists for approximately 5 days [10]. We investigated patient diaries (Figure 2) for CINV symptoms over 5 consecutive days. CINV has an acute phase occurring within 24 h of anticancer agent administration and a delayed phase occurring on days 2–5 following administration. In the present trial, we conducted our evaluation using the day of administration as the acute phase, the period from day 2 to day 5 following administration as the delayed phase, and the period from the day of administration to day 5 as the overall phase (OP). Nausea and general condition were assessed using a visual analog scale

Material and methods Subjects in this study comprised 41 patients who consented to participate in a clinical trial involving 71 courses of CDDP-based chemotherapy in the Department of Head and Neck Surgery of Tokyo Medical University’s Hachioji Medical Center from July 2012 to September 2013. The specific regimens were induction chemotherapy consisting of CDDP, docetaxel (DOC) and 5-fluorouracil (5-FU); radical therapy consisting of CDDP, DOC, and 5-FU in combination with radiotherapy [7–9]; and postoperative therapy using CDDP in combination with radiotherapy. In the induction chemotherapy, CDDP and DOC were both administered at 60 mg/m2 on day 1 and 5-FU at 800 mg/m2 from day 1 to day 5. As for the regimen of CDDP, DOC, and 5-FU in combination with radiotherapy, a total dose of 60 Gy was Induction chemotherapy Chemotherapy ↓ Cisplatin (60 mg/m2) ↓ Docetaxel (60 mg/m2) 5-Fluorouracil(800 mg/m2) ↓ ↓ ↓ ↓ ↓ Day

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Radiotherapy with chemotherapy Radiotherapy (2 Gy/day) Chemotherapy ↓ Cisplatin (60 mg/m2) ↓ Docetaxel (50 mg/m2) 5-fluorouracil (600 mg/m2) ↓ ↓ ↓ ↓ Day 1234

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Postoperative chemotherapy Radiotherapy (2 Gy/day) Chemotherapy Cisplatin (80 mg/m2) ↓ Day 1234 ••

36

14

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28

↓ ↓ ↓ ↓ ↓ ↓ 42 43 44 45 • • 56

↓ ••

42

1 h before cisplatin (day 1), patients received fosaprepitant (150 mg); 30 min before cisplatin, patients received palonosetron (0.75 mg) and dexamethasone (9.9 mg).On days 2 and 3, dexamethasone (6.6 mg) was administered in the morning. Figure 1. Chemotherapy regimens.

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K. Tsukahara et al. 1. In the 21 h since you started taking capsules, how bad was the worst feeling of nausea? Check the degree of nausea on the sacle below. No nausea 0

Felt really terrible 1

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3

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5

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7 8

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2. Did you vomit during the 24 h since you started taking the capsules? Didn’t vomit Vomited once or twice Vomited 6 or more times

Vomited 3~5 times

3. Did you take medicine to suppress nausea or vomiting? Take medicine

Didn’t take medicine

4. Amount of food eaten in the 24 h No different from normal About half normal amount

Somewhat less than normal Hardly any food or liquid

5. Please check your present physical condition on the scale below. No problem 0

1

Feel really terrible 2

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9

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Figure 2. Form for patient diaries.

(VAS) from 0 to 100 mm. No nausea was taken as 0, slight nausea as ‡ 0 but

Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas.

Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma...
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