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. 2014 Apr 24;5(5):390-7.
doi: 10.7150/jca.7706. eCollection 2014.

Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients

Yumiko Sato  1 , Masahiro Kondo  2 , Atsushi Inagaki  3 , Hirokazu Komatsu  4 , Chika Okada  5 , Kumi Naruse  6 , Tomoyo Sahashi  6 , Junko Kuroda  2 , Hiroka Ogura  3 , Shiori Uegaki  4 , Tatsuya Yoshida  4 , Yoshinori Mori  4 , Hiroo Sawada  7 , Shoichi Watanabe  8 , Hiroshi Sugiura  9 , Yumi Endo  10 , Nobuyasu Yoshimoto  10 , Tatsuya Toyama  10 , Shinsuke Iida  11 , Koichi Yamada  1 , Kazunori Kimura  2 , Atsushi Wakita  3
Affiliations

Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients

Yumiko Sato et al. J Cancer. .

Abstract

Background: Fosaprepitant-associated injection site reaction (ISR) has been reported in patients treated with cisplatin, an irritant drug. We conducted this retrospective study to clarify the incidence and symptoms of fosaprepitant-associated ISR in patients treated with anthracycline.

Patients and methods: Fifty six patients receiving 159 injections administering doxorubicin/cyclophosphamide (AC), fluorouracil/epirubicin/cyclophosphamide (FEC), or rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-)CHOP regimen through a peripheral vein at ambulatory treatment centers reviewed for this study from patients' medical records. Incidence of ISR was compared between 24 patients with fosaprepitant injection (fosaprepitant group) and 32 patients without fosaprepitant (control group). Frequency and symptoms of ISR per injection were also compared between 61 injections with fosaprepitant and 98 injections without fosaprepitant.

Results: Both the ISR incidence rate per patient and per injection were significantly higher in the fosaprepitant group than in the control group (67% vs. 16%; P=0.0002, 34% vs. 8.2%; P<0.0001, respectively). By multivariate analysis, fosaprepitant injection was found to be a significant independent variable correlated with ISR risk. Symptoms observed in 61 injections of fosaprepitant were pain (n=14, 23%), erythema (n=10, 16%), swelling (n=6, 10%), and delayed drip infusion (n=6, 10%). After the observation period, no ISR occurred when the administration route was changed to central venous injection or oral aprepitant was administered despite the continuation of chemotherapy.

Conclusion: ISR occurred more frequently and severely when fosaprepitant was injected through the peripheral vein in patients treated with anthracyclines compared to those without fosaprepitant.

Keywords: Antiemesis; anthracycline; fosaprepitant; injection site reaction; venous toxicity.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Schema of treatment regimen. Fosaprepitant, 5-HT3RA (FEC, AC: palonosetron 0.75 mg/body, (R-)CHOP: granisetron 3 mg/body), and/or dexamethasone 9.9 mg/body were administered to patients (fosaprepitant group), while only 5-HT3RA (FEC, AC: palonosetron 0.75 mg/body, (R-)CHOP: granisetron 3 mg/body) and/or dexamethasone 9.9 mg/body were administered to the control group via peripheral venous route for premedication of a particular chemotherapy (AC, FEC or (R-)CHOP). fAPR, fosaprepitant; NS, normal saline; 5-HT3RA, 5-hydroxytryptamine-3 receptor antagonist; DEX, dexamethasone; EPI, epirubicin; DXR, doxorubicin; VCR, vincristine; iv, intravenous injection; CPA, cyclophosphamide; and 5-FU, 5-fluorouracil.
Figure 2
Figure 2
Comparison of the incidence of ISR with or without administration of fosaprepitant: (A) per patient, (B) per injection. ISR was evaluated according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. Black bars represent the incidence of treatment-required ISR, and gray bars represent the incidence of non-treatment required ISR. ISR, injection site reaction; and fAPR, fosaprepitant.
Figure 3
Figure 3
Clinical symptoms (A) and managements of ISR (B). The frequency of (A) clinical symptoms and (B) managements of ISR was assessed for 61 injections in the fosaprepitant group and 98 injections in the control group. Black bars represent the frequency of symptoms or managements together with treatment-required ISR, and gray bars represent the frequency of clinical symptoms or managements together with non-treatment required ISR. * depicts the phenomenon observed without the handle of clinical staffs. ISR, injection site reaction; and fAPR, fosaprepitant.
Figure 4
Figure 4
The ISR monitoring of patients who experienced ISR during or after the observation period. After the observation period, we monitored the occurrence of ISR in patients who experienced ISR during the observation period. Patients who experienced ISR from fosaprepitant injection did not develop ISR again when they received subsequent chemotherapy with peroral administration of aprepitant. Gray panels indicate patients who experienced ISR; and white, patient had no ISRs. fAPR, fosaprepitant; APR, aprepitant; PV, peripheral vein; CV, central venous; and ISR, injection site reaction.
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