European Journal of Pharmacology 722 (2014) 165–171

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European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar

Review

Radiation induced nausea and vomiting Petra Feyer a, Franziska Jahn b, Karin Jordan b,n a b

Department of Radiotherapy, Vivantes Medical Center Berlin-Neukölln, Berlin, Germany Department of Hematology/Oncology, Martin-Luther-University Halle/Wittenberg, Halle/Saale 06120, Germany

art ic l e i nf o

a b s t r a c t

Article history: Accepted 27 September 2013 Available online 21 October 2013

Radiation induced nausea and vomiting (RINV) is a frequent complication of radiotherapy and still often underestimated by radiation oncologists. Fractionated RT may involve up to 40 fractions over a 6–8 weeks period, and prolonged symptoms of nausea and vomiting affect quality of life. Approximately, 50– 80 percent of patients undergoing radiotherapy (RT) will experience these symptoms if no appropriate prophylaxis is applied. The incidence and severity are influenced by the specific RT regimen and by patient-specific factors. Patients should receive antiemetic prophylaxis as suggested by the international antiemetic guidelines based upon a risk assessment, taking especially into account the planned radiotherapy regimen. In this field the guideline from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Clinical Oncology (ESMO) and the American Society of Medical Oncology (ASCO) guidelines are wildly endorsed. The emetogenicity of radiotherapy regimens and recommendations for the appropriate use of antiemetics including 5-hydroxytryptamine (5-HT3) receptor antagonists and steroids will be discussed in regard to the applied radiotherapy or radiochemotherapy regimen. & 2013 Elsevier B.V. All rights reserved.

Keywords: Radiation therapy Nausea Vomiting Antiemetics Risk factors

Contents 1. 2. 3. 4. 5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Incidence of RINV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk classification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevention and treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. 5-HT3 receptor antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. Tachykinin NK1 receptor antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4. Other agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5. Duration of prophylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6. Rescue therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Guidelines and patient management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1. High risk setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2. Moderate risk setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3. Low risk setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4. Minimal risk setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.5. Concomitant chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

165 166 166 166 166 167 168 168 169 169 169 169 169 170 170 170 170 170 170

1. Introduction n

Correspondence to: Department of Internal Medicine IV, Oncology/ Hematology, Martin-Luther-University Halle/Wittenberg, Ernst-Grube-Str. 40, 06120 Halle/Saale, Germany. Tel.: þ 49 345 557 2924; fax: þ 49 345 557 2950. E-mail address: [email protected] (K. Jordan). 0014-2999/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejphar.2013.09.069

Nausea and vomiting caused by radiation therapy (RT) are clinically important and can be very distressing for patients. Especially patients receiving total body irradiation, half body irradiation

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or abdominal radiotherapy are at a great risk of nausea and vomiting. Insufficient control of these symptoms can result in potentially lifethreatening medical conditions, including dehydration and electrolyte imbalance. Although those intensive treatments have become more uncommon results of representative observational studies propose up to 80 percent overall cumulative incidence rate of some degree of nausea and vomiting among patients undergoing radiotherapy (Feyer et al., 2011). Anyhow for patients even a mild nausea or vomiting might be burdensome and can cause a delay or refuse of further treatment. The incidence, classification of risk, and management of radiation therapy induced nausea and vomiting (RINV) will be discussed in this review.

2. Pathophysiology The pathophysiology of Radiotherapy induced nausea and vomiting (RINV) is still incompletely understood. As it is thought to be similar to chemotherapy induced nausea and vomiting (CINV) the therapeutic options are also related. In depth details of CINV are discussed elsewhere in this special edition. Progress in understanding the pathophysiology of chemotherapy-induced emesis led to the development of agents that form also the basis for the treatment of RINV.

to be the radiation field. The recent guidelines from the Multinational Association for Supportive Care in Cancer (MASCC) and the European Society for Medical Oncology (ESMO), which have been subsequently endorsed by the American Society of Clinical Oncology (ASCO) in 2011, divide the risk of emesis due to RT into four categories as shown in Table 1 (Basch et al., 2011; Feyer et al., 2011). However, it should be a matter of discussion if the risk classification should precisely also include the risk of nausea, as some risk factors (e.g. pelvis, cranium) categorized by the risk of nausea rather than emesis (Maranzano et al., 2010). The risk of nausea and vomiting for a patient being treated with RT depends upon multiple other factors in addition to the emetogenicity of the specific RT regimen. Patient-specific factors include the simultaneous administration of chemotherapy as another prominent risk factor and also age, gender, alcohol consumption, anxiety, and previous experience of RINV or CINV (Table 2) (Feyer et al., 2005; Jordan et al., 2009; Maranzano, 2001). The four risk categories based upon the RT regimen can be modified to incorporate these patient-specific factors. Although not prospectively proven, an approach taking these risk factors into account might further improve emesis prophylaxis in patients receiving RT (Fig. 1). In spite of the potential benefit of this patient tailored approach, the current guidelines do not use this proposed multifactor risk categories, due to the lack of validation. However, a risk factor centered antiemetic prophylaxis approach seems also critical in patients with CINV (Warr et al., 2011).

3. Incidence of RINV 5. Prevention and treatment As there is a large amount of literature regarding antiemetic therapies to prevent CINV the body of evidence related to RINV is noticeable smaller (Dennis et al., 2011). Two prospective observational studies provide information on the frequency of RINV and antiemetic measures: The Italian Group for Antiemetic Research in Radiotherapy (IGARR) analyzed the incidence of RINV in 1020 patients receiving various kinds of RT (Maranzano et al., 2010). Overall, nausea and/ or vomiting were reported by 28 percent. The median time to the first episode of vomiting was three days. Antiemetic drugs were administered to 17 percent of the patients, including 12 percent treated prophylactically and 5 percent given rescue therapy. In a second cohort of 368 patients receiving RT, the overall incidence rates for nausea and vomiting were 39 and 7 percent (Enblom et al., 2009). Nausea was more frequent in those receiving RT to the lower abdomen or pelvis (66 percent) compared to the head and neck area radiated patients (48 percent).

4. Risk classification First of all the treatment (irradiated site and volume, single and total dose, fractionation schedule, techniques) determines the incidence and severity of RINV. The most important factor appears

Discussing prevention and treatment of RINV it is necessary to know that there are only few randomized trials evaluating the Table 2 Individual risk factors. Risk factor

Risc score

Age 455 years o 55years

0 1

Sex Male Female

1 2

Alcohol consumption Yes ( 4 100 g/day) No

0 1

Previous nausea and vomiting Yes No

1 0

Anxiety Yes No

1 0

Risk profile (4 ¼ normal risk | 5–6 high risk).

Table 1 Risk categories. Emetogenic potential

Risk of emesis without antiemetic prophylaxis (percent)

Location

High Moderate

Risk 490 Risk 60 to 90

Low

Risk 30 to 60

Minimal

Risk o 30

Total body irradiation (TBI), Total nodal irradiation (TNI) Upper abdominal irradiation, hemi-body irradiation (HBI) and upper body irradiation (UBI) Cranium (all), craniospinal, head and neck, lower thorax region, pelvis Breast and extremities

P. Feyer et al. / European Journal of Pharmacology 722 (2014) 165–171

167

Risk evaluation of emetogenic potential

Emetogenic potential of radiotherapy

Risk score of patients (points)

Feyer PC, Maranzano E, Molassiotis A, Roila F, Clark-Snow RA, Jordan K. Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy: update 2009. Support Care Cancer. 2011; 19 Suppl 1: S5-14 Feyer P. The importance of simple, easy-to-follow antiemetic guidelines. Acta Oncol. 2004; 43 Suppl 15: 5-8.

Fig. 1. Risk evaluation and emetogenic potential.

Table 3 Randomized trials with 5-HT3 receptor antagonists and upper abdomen irradiation (Feyer et al., 2011). Author (reference)

Number of patients

Radiotherapy

Antiemetic prophylaxis

Complete response

Results

Priestman et al. (1990) Priestman et al. (1993) Bey et al. (1996)

N ¼ 82

8–10 Gyr single fraction

OND 8 mg  3/day p.o. for 5 days MCP 10 mg  3/day p.o. for 5 days

97% 46%

OND better than MCP1).1).

N ¼ 135

1.8 Gyr/day for at least 5 fractions

OND 8 mg  3/day p.o. MCP 10 mg  3/day p.o.

61% 35%

OND better than MCP (for vomiting)

N ¼ 50

At least 6 Gyr single fraction

At least 1.7 Gyr/day for Z 10 fractions

100%a 93%a 83%a 54%a 67% 45%

DOL better than placebo

N ¼ 111

DOL 0.3 mg/kg i.v. DOL 0.6 mg/kg i.v. DOL 1.2 mg/kg i.v. Placebo OND 8 mg  2/day p.o. Placebo

N ¼ 23

2 Gyr/day to 30 Gyr in 15 fractions 10–30 fractions (1.8–3 Gyr/fraction)

91% 50% 57.5% 42%

TRO better than MTC

N ¼ 260

TRO 5 mg/day p.o. MTC 10 mg  3/day p.o. GRAN 2 mg/day Placebo

N ¼ 154

At least 5 fractions to minimum total DEX 2 mg  3/day p.o. for 5–7 days dose of 20 Gyr Placebo

70% 49%

DEX better than placebo

N ¼ 211

Z15 fractions to the upper abdomen to a dose of 20 or more Gyr

OND 8 mg bid for 5 daysþ Placebo for 5 days

ONDþDEX better than OND alone

Fractionated radiotherapy of moderate or high emetogenic potential

5 mg TRO daily starting 1 day before radiotherapy until 7 days after end of radiotherapy 5 mg TRO on an as needed base

71%a 12%b 78%a 23%b Incidence of vomiting was 2.19 (p ¼0.001) times higher in the rescue TRO arm

Franzen et al. (1996) Aass et al. (1997) Lanciano et al. (2001) Kirkbride et al. (2000) Wong et al. (2006)

Mystakidou et al. (2006)

N ¼ 288

OND 8 mg bid þDEX 4 mg for 5 days

OND better than placebo

GRAN better than placebo

Prophylactic TRO better than rescue TRO

OND ondansetron, MCP metoclopramide, DOL dolasetron, PCP prochlorperazine, TRO tropisetron, DEX dexamethasone, p.o. orally, i.v. intravenously a Complete plus major response. a b

Primary endpoint: CR day 1–5. Secondary endpoint: CR day 1–15.

efficacy of antiemetic drugs in preventing RINV (Tables 3 and 4) and that these trials were conducted in patients with moderate or high risk for RINV. The most studied agents in these settings seem to be 5-hydroxytryptamine (5-HT3) receptor antagonists, proving good response and activity. Other agents such as the tachykinin NK1 receptor antagonist may play a role but these agents’ needs to be further studied.

5.1. 5-HT3 receptor antagonists In a recent meta-analysis, including nine trials, the antiemetic properties of 5-HT3 receptor antagonists were analyzed (Salvo et al., 2012). As expected a good response concerning the control of emesis was achieved: Compared with placebo fewer patients had residual emesis (40 versus 57 percent, relative risk [RR] 0.7, 95

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Table 4 Randomized clinical trials with 5-HT3 receptor antagonists for total-body irradiation or half-body irradiation (Feyer et al., 2011). Author (reference)

Number of patients Radiotherapy

Tiley et al. (1992)

N ¼ 20

Spitzer et al. (1994)

N ¼ 20

Prentice et al. (1995) N ¼ 30

Huang et al. (1995) Sykes et al. (1997)

N ¼ 116 N ¼ 66

Spitzer et al. (2000)

N ¼ 34

Antiemetic prophylaxis

10.5 Gyr OND 8 mg i.v. TBI single fraction Placebo 1.2 Gyr  3/day OND 8 mg  3/day p.o. TBI 11 fractions to a total Placebo dose of 13.2 Gyr 7.5 Gyr GRAN 3 mg i.v. versus TBI single fraction MTC 20 mg i.v. plus DEX 6 mg/m2 i.v. plus LOR 2 mg i.v. 7–7.7 Gyr OND 8 mg (i.v.?) plus 8–12.5 Gyr OND 8 mg  2 p.o. versus HBI single fraction CLP 25 mg  3 p.o. plus DEX 6 mg  3 p.o. 1.2 Gyr  3/day OND 8 mg  3/day p.o. versus TBI 11 fractions to a total GRAN 2 mg  1/day p.o. dose of 13.2 Gyr

Complete response (%) Results 90a 50a 50 0

OND better than placebo OND better than placebo

53 13

GRAN better than MTC þ DEXþ LOR

84 94 34

ONDþDEX better than paspertin þ DEX OND better than CLPþ DEX

47 61

No difference

TBI total-body irradiation, HBI half-body irradiation, OND ondansetron, GRAN granisetron, MTC metoclopramide, LOR lorazepam, CLP chlorpromazine, DEX dexamethasone, p. o. orally, i.v. intravenously a

All patients received intravenous dexamethasone (8 mg) and phenobarbitone (60 mg/m2).

percent CI 0.57–0.86) and less patients required rescue medication (6.5 versus 36 percent, RR 0.18, 95 percent CI 0.05–0.60). In accordance to CINV the control of nausea seems to be more difficult: Most patients did develop RT-induced nausea despite treatment (70 versus 83 percent with placebo, RR 0.84, 95 percent CI 0.73–0.96). In summary, these trials show patients receiving upper abdomen irradiation have a greater benefit using 5-HT3 receptor antagonists than metoclopramide, phenothiazines or placebo to control RINV (Aass et al., 1997; Bey et al., 1996; Franzen et al., 1996; Lanciano et al., 2001; Priestman et al., 1990, 1993). Similarly, 5-HT3 receptor antagonists provided significantly better protection against RINV caused by TBI or HBI than conventional antiemetics or placebo (Table 4) (Prentice et al., 1995; Spitzer et al., 1994, 2000; Sykes et al., 1997; Tiley et al., 1992). Separate analyses of trials comparing 5-HT3 receptor antagonists with metoclopramide also demonstrated a statistically significant benefit for the control of vomiting. The adverse effects of 5-HT3 receptor antagonists are generally mild, consisting mainly of headache, constipation, and asthenia (Goodin and Cunningham, 2002; Jordan et al., 2007; Prentice et al., 1995; Priestman et al., 1993; Spitzer et al., 2000). In some patients, 5-HT3 receptor antagonists reduced the frequency of diarrhea, a troublesome side effect due to acute radiation enterotoxicity (Feyer et al., 1998; Franzen et al., 1996). Randomized trials in RINV have utilized four different 5-HT3 receptor antagonists (ondansetron, granisetron, dolasetron, tropisetron). There is still no data comparing those different 5-HT3 receptor antagonists and data to define optimal doses and schedules are also missing (Salvo et al., 2012). A systematic review including 25 randomized and non-randomized trials revealed that 5-HT3 receptor antagonists were most commonly administered for the entire duration of a course of radiotherapy. Thus we still leaking of evidence of knowledge related duration and timing of 5-HT3 receptor antagonist therapy (Dennis et al., 2012). To develop effective and cost-efficient antiemetic strategies further studies comparing different application intervals are still needed. With regard to palonosetron, the newest 5-HT3 receptor antagonist, no fully published studies are currently available on the appropriate dosing and frequency in the RINV setting in contrast to the CINV setting. However, the updated ASCO guideline suggests that dosing every second or third day may be appropriate for this agent (Basch et al., 2011).

5.2. Corticosteroids Corticosteroids are an attractive therapeutic antiemetic option because of their widespread availability and low cost. For short term use the side effects are rather low and do not outweigh the benefit of these agents. One randomized trial showed that dexamethasone was significantly more effective than placebo in patients receiving RT of the upper abdomen (Table 3) (Kirkbride et al., 2000). Combining corticosteroids with a 5-HT3 receptor antagonists was assessed in a well-designed, randomized trial in which a fiveday course of dexamethasone plus ondansetron was compared to ondansetron plus placebo in 211 patients who received RT to the upper abdomen (Table 3) (Wong et al., 2006). During the first five days, there was a statistically non-significant trend toward complete control of nausea (50 versus 38 percent with placebo) and vomiting (78 versus 71 percent), which was the primary objective of the trial. The effects of dexamethasone extended beyond the initial five day period, and significantly more patients had complete control of emesis over the entire course of radiotherapy (23 versus 12 percent, with placebo), a secondary objective of the trial. Thus this study demonstrates that the addition of dexamethasone has a modest effect on RT induced nausea and vomiting and is potentially a useful addition to a 5-HT3 receptor antagonists within this setting. Furthermore, since emesis is more frequent in early phase of treatment, prophylactic antiemetics may not be necessary for a full course of RT, and treatment for the first week may be sufficient (Basch et al., 2011; Feyer et al., 2011; Kirkbride et al., 2000). 5.3. Tachykinin NK1 receptor antagonists Tachykinin NK1 receptor antagonists, namely aprepitant and fosaprepitant have an established role in the management of CINV, as discussed also in this issue. So far, there are no studies that have evaluated the impact of this drug class solely on the risk of RINV. Although preclinical data indicate that RINV is mediated in part by substance P (Yamamoto et al., 2005), these agents still cannot be recommended at this time. Therefore, tachykinin NK1 receptor antagonists are not reflected in the actual antiemetic guidelines. Data from a small clinical trial (n ¼59 patients) presented at the MASCC meeting 2011 provides a first hint that tachykinin NK1 receptor antagonists

P. Feyer et al. / European Journal of Pharmacology 722 (2014) 165–171

in combination with 5-HT3 receptor antagonists and dexamethasone proved to be advantageous in the prophylaxis of acute and delayed nausea during simultaneous radio-chemotherapy compared with the standard antiemetic treatment. More patients on the emetic prophylaxis containing tachykinin NK1 receptor antagonists reached a complete response (Riesner et al., 2011).

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5.6. Rescue therapy The benefit of 5-HT3 receptor antagonists once nausea or vomiting occurs has been suggested in all studies, but there are no trials specifically in this setting (LeBourgeois et al., 1999; Maranzano et al., 2005; Mystakidou et al., 2006). The emerging role of olanzapine in breakthrough emesis in patients with CINV has not been studied in RINV yet (Navari et al., 2013).

5.4. Other agents Older, less specific antiemetic drugs such as prochlorperazine, metoclopramide, and cannabinoids have shown limited efficacy in the prevention or treatment of RINV, although they may have a role in patients with milder symptoms and as rescue agents (Roila et al., 1998).

5.5. Duration of prophylaxis The appropriate duration of antiemetic prophylaxis for patients receiving fractionated radiotherapy is not clear. There have been no randomized trials using 5-HT3 receptor antagonists that compared a five-day course of treatment with a more protracted course. A systematic review including 25 randomized and nonrandomized trials revealed that 5-HT3 receptor antagonists were most commonly administered for the entire duration of a course of radiotherapy. Thus we still leaking of evidence related duration and timing of 5-HT3 receptor antagonist therapy (Dennis et al., 2012). Although a lack of evidence the current guidelines recommended, that the decision on whether or not to continue antiemetic prophylaxis beyond the first week should be based upon an assessment of the risk of emesis as well as relevant individual factors.

6. Guidelines and patient management The development of new antiemetic agents and a better understanding of their activity as a function of the emetogenicity of different RT regimens have led to the generation of guidelines for patient management. The most recent guidelines were promulgated by the Multinational Association for Supportive Care in Cancer (MASCC) and European Society for Medical Oncology (ESMO) in 2009 (Feyer et al., 2011) and which were subsequently endorsed by the American Society of Clinical Oncology (ASCO) in 2011 (Basch et al., 2011). In summary, these guidelines are presented and incorporated into the following (Table 5). 6.1. High risk setting For patients at high risk of developing RINV (Table 5), a prophylaxis with a 5-HT3 receptor antagonist is recommended by the guidelines. Based upon results from patients receiving highly emetogenic chemotherapy, the addition of dexamethasone to the 5-HT3 receptor antagonist is suggested. There are no fully published comparative clinical trials on the use of tachykinin NK1 receptor antagonists in preventing RINV and its use can therefore not be recommended.

Table 5 Antiemetic dosing by radiation risk category (ASCO Guidelines (Basch et al., 2011)). Risk category

Dose

High emetic risk 5-HT3 receptor antagonist Granisetrona Ondansetrona Palonosetronb Dolasetron Tropisetron Corticosteroid Dexamethasone Moderate emetic risk 5-HT3 receptor antagonist Corticosteroid Dexamethasone Low emetic risk 5-HT3 receptor antagonist

Minimal emetic risk 5-HT3 receptor antagonist

Dopamine receptor antagonist Metoclopramide Prochlorperazine

Schedule

5-HT3 receptor antagonist before each fraction throughout XRT; continue for at least 24 h after completion of XRT 2 mg oral; 1 mg or 0.01 mg/kg IV 8 mg oral twice daily; 8 mg or 0.15 mg/kg IV 0.50 mg oral; 0.25 mg IV 100 mg oral only 5 mg oral or IV 4 mg oral or IV

During fractions 1–5

Any of the above listed agents are acceptable; note preferred optionsb

5-HT3 receptor antagonist antagonist before each fraction throughout XRT

4 mg IV or oral

During fractions 1–5

Any of the above listed agents are acceptable; note preferred options

5-HT3 receptor antagonist either as rescue or prophylaxis; if rescue is used, then prophylactic therapy should be given until the end of XRT

Any of the above listed agents are acceptable; note preferred options

Patients should be offered either class as rescue therapy; if rescue is used, then prophylactic therapy should be given until the end of XRT

20 mg oral 10 oral or IV

Abbreviations: 5-HT3, 5-hydroxytryptamine-3; IV, intravenous; XRT, radiation therapy. a

Preferred agents. No data are currently available on the appropriate dosing frequency with palonosetron in this setting. The Update Committee suggests that dosing every second or third day may be appropriate for this agent. b

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6.2. Moderate risk setting For patients at moderate risk of developing RINV (Table 5), prophylaxis with a 5-HT3 receptor antagonist is the prophylaxis of choice. However, in this risk group, the addition of short course dexamethasone to the 5-HT3 receptor antagonist may be offered during fraction 1–5. 6.3. Low risk setting For patients at low risk of developing RINV (Table 5), prophylaxis with a 5-HT3 receptor antagonist is suggested. Based upon an individualized assessment of risk, observation with rescue treatment using a 5-HT3 receptor antagonist if necessary is an appropriate alternative. 6.4. Minimal risk setting For patients at minimal risk of developing RINV (Table 5), a prophylactic antiemetic treatment is not necessary. If patients develop RINV treatment with a dopamine receptor antagonist or a 5-HT3 receptor antagonist might be appropriate. 6.5. Concomitant chemotherapy For patients being treated with concomitant RT and chemotherapy, antiemetic prophylaxis should be based upon the higher chemotherapy or RT risk category.

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Radiation induced nausea and vomiting.

Radiation induced nausea and vomiting (RINV) is a frequent complication of radiotherapy and still often underestimated by radiation oncologists. Fract...
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