INTRODUCTION — Few side effects of cancer treatment are more feared by patients than nausea and vomiting. Although nausea and emesis (vomiting and/or retching) can result from surgery or radiation therapy, chemotherapy-induced nausea and vomiting (CINV) is potentially the most severe and most distressing.
The objective of prophylactic antiemetic therapy is the complete prevention of CINV, and this should be achievable in the majority of patients receiving chemotherapy, even with highly emetogenic agents. However, many patients experience clinically significant CINV (poorly controlled or "breakthrough" CINV) despite the use of guideline-directed, appropriate prophylaxis. For these patients, immediate treatment with additional antiemetics is indicated, followed by a reassessment of the adequacy of the prophylactic regimen.
Management of poorly controlled or breakthrough CINV will be reviewed here. Prevention of CINV in adult patients receiving cancer chemotherapy is reviewed separately as is the pathophysiology of CINV, the characteristics of antiemetic drugs, and nausea and vomiting associated with radiation therapy and opioid analgesics. (See "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting" and "Characteristics of antiemetic drugs" and "Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment" and "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Nausea and vomiting'.)
PROPHYLAXIS FOR CINV — Antiemetics are most effective when given prophylactically, and it is preferable to use maximally effective antiemetics as first-line therapy rather than withholding them for later use at the time of antiemetic failure (ie, breakthrough or poorly controlled CINV) [1]. Guidelines for prophylactic antiemetic therapy for intravenously administered chemotherapy according to the estimated risk of CINV are available from the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network, and in a year 2016 update of recommendations from the Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) [1-4]. Our approach to prophylaxis, which largely parallels recommendations from MASCC/ESMO and ASCO, is summarized in the following sections and outlined in the accompanying table (table 1).
Despite the use of guideline-directed, appropriate antiemetic prophylaxis, as many as 30 to 40 percent of patients experience clinically significant CINV, particularly those individuals receiving highly emetogenic chemotherapy regimens (eg, those containing cisplatin or a combination of cyclophosphamide and doxorubicin). Delayed nausea is a particular problem, since conventional antiemetics are more successful at preventing emesis than at preventing nausea, particularly delayed nausea.
Prevention of CINV is discussed in detail elsewhere. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)
MANAGEMENT OF POORLY CONTROLLED AND BREAKTHROUGH CINV
Initial evaluation — For patients with breakthrough CINV, clinicians should reevaluate disease status, concurrent illnesses and medications, the emetic risk of the chemotherapy regimen, and ascertain that the best regimen was administered for that regimen.
Examples of other disease- and medication-related causes for emesis include:
●The use of opioid analgesics (see "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Nausea and vomiting')
●Certain antibiotics (eg, erythromycin), and infectious causes (see "Approach to the adult with nausea and vomiting", section on 'Acute disorders')
●Central nervous system metastases (see "Epidemiology, clinical manifestations, and diagnosis of brain metastases", section on 'Clinical manifestations')
●Gastrointestinal obstruction (see "Palliative care of bowel obstruction in cancer patients" and "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults")
●Gastroparesis (see "Gastroparesis: Etiology, clinical manifestations, and diagnosis")
●Hypercalcemia (see "Clinical manifestations of hypercalcemia")
●Abdominopelvic radiation therapy (see "Overview of gastrointestinal toxicity of radiation therapy" and "Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment")
Assuming that other disease and medication-related issues are excluded, it is important to ensure that the patient received the antiemetic regimen appropriate for the drug(s) being given (table 2 and table 3) at the correct dose and schedule (table 1). As an example, if the recommended prophylactic regimen included a glucocorticoid on days 2 to 4 to prevent delayed emesis, and it was not administered, it should be given. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Prevention of delayed emesis'.)
Treatment
Olanzapine — For most patients who experience nausea or vomiting despite optimal prophylaxis for CINV and who did not receive olanzapine with the initial prophylactic regimen, we suggest olanzapine rather than a different rescue antiemetic, in addition to continuing the standard antiemetic regimen. The use of a 5 mg rather than 10 mg dosing regimen may reduce treatment-related sedation.
Olanzapine is a second-generation antipsychotic that blocks serotonin type two 5-hydroxytryptamine (5-HT2) receptors and dopamine D2 receptors. Olanzapine is an effective rescue emetic for refractory CINV, achieving complete control of nausea and emesis in 50 to 70 percent of patients [5,6]. In the only published randomized trial conducted in patients receiving standard dose chemotherapy, superiority for olanzapine (10 mg orally, daily for three days) over metoclopramide (10 mg orally, three times daily for three days) for treatment of breakthrough nausea and vomiting was shown in a double-blind randomized trial involving 80 patients receiving highly emetogenic chemotherapy [7]. During the 72-hour observation period, significantly more patients receiving olanzapine had no recurrent emesis (70 versus 31 percent) and no nausea (68 versus 23 percent). Fewer than 2 percent of patients receiving olanzapine reported sedation on days 1 or 3. There were no grade 3 or 4 adverse effects in either group, and symptom scores, such as sedation, did not differ significantly.
The optimal dose for olanzapine is not definitively established. We generally prefer the 5 mg dose, at least initially, to diminish the likelihood of treatment-related somnolence. A year 2018 review of olanzapine for CINV prophylaxis concluded that there is insufficient evidence to exclude the possibility that 5 mg doses may confer a lower risk of somnolence or fatigue as compared with 10 mg doses [8]. However, a later randomized phase II trial not included in the analysis concluded that a lower prophylaxis dose (5 mg orally, three times a day for three days) provides similar antiemetic efficacy with a more favorable side effect profile than a 10 mg dose [9]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)
Alternative conventional antiemetics — For patients who experience nausea or vomiting despite optimal prophylaxis for CINV and who previously received olanzapine, they may be offered an antiemetic of a different class than was administered with the prophylactic regimen, in addition to continuing the standard antiemetic regimen. Options include a neurokinin-1 receptor (NK1R) antagonist, lorazepam or alprazolam, a dopaminergic antagonist (eg, prochlorperazine, thiethylperazine, haloperidol), or an alternative type of type three 5-hydroxytryptamine (5-HT3) antagonist than was administered initially.
With the exception of the single trial, described above comparing ondansetron with metoclopramide [7], there are no randomized trials that have investigated or compared the benefits of other conventional antiemetics in the management of breakthrough CINV, and the literature on benefit from specific strategies is sparse. (See 'Olanzapine' above.)
Older agents that were previously used for prevention of CINV have generally not been formally studied for the treatment of established CINV in the context of modern prophylactic regimens that include a 5-HT3 antagonist plus dexamethasone with or without a NK1R antagonist.
Scattered case reports and small series support benefit for lorazepam [10], prochlorperazine [11], a 5-HT3 antagonist [11,12], a transdermal topical gel containing lorazepam, diphenhydramine and haloperidol [13], NK1R antagonists [14,15], and metoclopramide plus methylprednisolone [16]. There are no data on the use of single-agent glucocorticoids in this setting.
Consensus-based guidelines from expert groups do not generally provide specific actionable recommendations for rescue medications:
●Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) guidelines suggest that when breakthrough emesis occurs, the prophylactic regimen for subsequent cycles should be changed by switching to a different 5-HT3 antagonist, substituting metoclopramide for the 5-HT3 receptor antagonist, or adding other agents such as dopamine antagonists or benzodiazepines, but they do not provide a specific recommendation for treating breakthrough CINV [1].
●Year 2020 guidelines from American Society of Clinical Oncology (ASCO) suggest that adults who experience nausea and/or vomiting despite optimal prophylaxis and who have already used olanzapine may be offered a NK1R antagonist, lorazepam or alprazolam, a dopaminergic antagonist (eg, prochlorperazine, thiethylperazine, haloperidol), or an alternative type of 5-HT3 antagonist than was administered initially [3].
●The National Comprehensive Cancer Network (NCCN) guidelines suggest treating breakthrough CINV with an agent from a drug class that was not used in the prophylactic regimen and recommend continuing the breakthrough medication with subsequent courses of chemotherapy if nausea and vomiting is controlled [4].
Cannabinoids and medical marijuana — Cannabinoids such as dronabinol and nabilone (where available) are an option for rescue antiemetics in patients with refractory nausea and vomiting, but the modest benefits are counterbalanced by an unfavorable side effect profile, especially in older patients. We do not offer use of medical marijuana or cannabidiol (CBD) oil for prevention or treatment of CINV. This recommendation is consistent with published antiemetic guidelines for managing CINV from the NCCN, ASCO, and the MASCC/ESMO, all of which support use of synthetic cannabinoids but not inhaled or ingested marijuana as a rescue antiemetic [1,3,4].
The potential antiemetic utility of cannabis and cannabinoids was first observed in scattered reports of improved emetic control in patients using marijuana during chemotherapy [17]. Since then, several randomized trials and meta-analyses have addressed the efficacy of synthetic cannabinoids for prevention and management of CINV, but little data on benefit from inhaled or ingested cannabis (medical marijuana).
Synthetic cannabinoids — Several randomized trials have explored the efficacy of synthetic cannabinoids (versus placebo or other antiemetics) for management of CINV, but none are high-quality controlled clinical trials comparing cannabinoids versus other rescue strategies in patients who are refractory to modern antiemetics. At least five meta-analyses have been conducted addressing benefit of synthetic cannabinoids for management of CINV [17-21]; and a meta-analysis of all five meta-analyses has also been undertaken.
●The 2018 meta-analysis of all five meta-analyses concluded that control of CINV was significantly better with synthetic cannabinoids versus placebo (7 controlled trials, 500 patients, risk ratio [RR] 3.60, 95% CI 2.55-5.09, with a number needed to treat [NNT] of 4), as well as versus other antiemetics (predominantly neuroleptics, 14 trials, 1022 patients, RR 1.85, 95% CI 1.18-2.91, NNT 7) [22]. In a broader analysis that included trials of cannabinoids for managing pain, spasticity, or CINV adverse effects were very common with synthetic cannabinoids, including dizziness (3 trials, 666 patients, RR 2.87, 95% CI 2.02-4.08, 32 versus 11 percent, number needed to harm [NNH] 5), sedation (15 trials, 1373 patients, relative risk 1.66, 95% CI 1.46-1.89, NNH 5), confusion (5 trials, 508 patients, RR 2.85, 95% CI 1.25-6.47, NNH 15), and dissociation (6 trials, 571 patients, RR 8.58, 95% CI 6.38-11.5, NNH 20). "Feeling high" during treatment was reported by 35 to 70 percent of users.
Despite these adverse effects, patient preference significantly favored the cannabinoid over both placebo (RR 4.82, 95% CI 1.74-13.36) and other antiemetics (RR 2.76, 95% CI 1.88-4.03) with available data all coming from one of the meta-analyses [21]. The quality of evidence ratings for benefit were modest for the comparison of cannabinoids versus placebo (downgraded because of serious risk of bias and imprecision); all other comparisons were low to very low quality evidence because of risk of bias, inconsistency, and imprecision. However, there was a large magnitude of effect.
Although concern about the abuse potential of cannabinoid drugs has slowed their development, a few synthetic cannabinoid-type drugs are commercially available, and others are under study. Guidelines from the NCCN, ASCO, and MASCC/ESMO [3,4] all state that cannabinoids such as dronabinol can be considered for refractory nausea and vomiting, and as a rescue antiemetic.
Dronabinol is approved in the United States for CINV in patients who have failed to respond adequately to conventional antiemetic treatments. In Canada and the UK, another oral cannabinoid (nabilone) is available, but this was discontinued in the United States in 2019. An oromucosal spray containing THC plus CBD (and smaller concentrations of other compounds), called nabiximols (Sativex), is also approved in Canada and elsewhere (but not yet in the United States) for treatment of neuropathic pain due to multiple sclerosis, but not refractory nausea and vomiting. However, it has been used off label for this purpose. It is rapidly absorbed from the buccal mucosa, and the dose can be self-titrated by the patient.
Medical marijuana — Although one of the most common reasons for patients to request access to medical marijuana is to relieve refractory nausea and vomiting [23], its value for the prevention and treatment of CINV remains uncertain. An early prospective, uncontrolled pilot study from 1988 found that inhaled cannabis was effective in 78 percent of 56 patients who had inadequate control of CINV with the conventional antiemetics that were available at that time [24], but there have been no subsequent clinical reports addressing efficacy of inhaled or ingested marijuana for CINV.
Medical use of smoked, vaporized, or ingested cannabis ("medical marijuana") is legal in several countries, including the Netherlands and Canada. Cannabis use is still illegal in the United States at the federal level (which considers marijuana a schedule I controlled substance) but is legal in most states. Clinicians may not prescribe cannabis but the states that have legalized medical use may rely on clinician assessment to determine eligibility for treatment and recommended formulation and dose.
Given the heterogeneous legal status of marijuana, especially within the United States, the differences in cannabinoid concentrations across strains of cannabis and available products [25], the inability to stipulate, know, or titrate the dose taken by the patient, the general paucity of evidence-based information about efficacy for CINV, and concerns about respiratory effects and cancer risk in cannabis smokers [26-32], we do not offer medical marijuana to patients with refractory CINV, even in jurisdictions where it is legal. However, given the state of the science and the sociopolitical complexities, each clinician must make his or her own decision about this issue while hopefully keeping an open mind. In jurisdictions where it is legal, should patients experience refractory CINV or report using and benefitting from medical marijuana, it is reasonable to accept a patient's decision to try medical cannabis and continue its use if it is helpful.
CBD oil — CBD (cannabidiol) is a naturally occurring molecule which is derived from cannabis but lacks tetrahydrocannabinol (THC) and thus has no psychoactive properties. It can be procured by patients from legal marijuana dispensaries, online companies, or street suppliers (CBD oil [nutraceutical]). An approved formulation of CBD oil (pharmaceutical) is now available in the United States as a purified product available by prescription (Epidiolex) and approved for treatment of some types of refractory epilepsy in children. (See "Dravet syndrome: Management and prognosis" and "Lennox-Gastaut syndrome".)
Although CBD oil (herbal) is used by patients as a nutraceutical for a variety of other conditions, there are few data on its benefits or risks in cancer patients, and use cannot be recommended. A single phase II randomized, double-blind, placebo-controlled trial of CBD oil for relief of symptoms in advanced cancer concluded that CBD oil did not add value to the reduction in symptom distress (including nausea and vomiting) provided by specialist palliative care [33].
Complementary therapies — For patients with CINV despite an adequate prophylactic regimen, there is insufficient evidence for a recommendation either for or against the use of ginger supplementation, acupuncture/acupressure, or other complementary therapies. However, given the low potential for harm, a trial of ginger supplementation or acupuncture/acupressure is reasonable for patients who desire it.
Ginger — Conventional antiemetics are more successful at preventing emesis than at preventing nausea. At least eight randomized placebo-controlled trials have studied the benefit of ginger (Zingiber officinale) as an aid to reduce nausea during chemotherapy, with mixed results. Five demonstrate at least some benefit [34-38], while three did not [39-41]:
●The largest trial randomly assigned 744 patients who experienced nausea following any chemotherapy cycle despite the use of a prophylactic antiemetic regimen to placebo or supplemental ginger (at doses of 0.5, 1, or 1.5 g twice daily) for six days, starting three days prior to the first day of the next two chemotherapy cycles [34]. All patients received a 5-HT3 receptor antagonist on day 1 of all cycles. Two-thirds of the enrolled patients were receiving chemotherapy for breast cancer. All doses of ginger were associated with a significant reduction in acute nausea throughout day 1 of the chemotherapy cycles, although the largest reduction was seen with the 0.5 and 1 g doses. The authors concluded that ginger supplementation significantly aids in reduction of day 1 nausea during chemotherapy.
●However, in contrast to these results, a benefit for ginger in addition to conventional antiemetics (5-HT3 antagonists and/or aprepitant) could not be shown in a randomized placebo-controlled phase II trial of 162 cancer patients who had suffered CINV during at least one prior cycle of chemotherapy [39]. In fact, patients who took ginger plus aprepitant had more severe acute nausea than did those who took only aprepitant.
Updated 2020 guidelines from ASCO state that the evidence is insufficient for a recommendation for or against use of ginger to prevent CINV [3]. On the other hand, in 2018, ASCO endorsed the Society for Integrative Oncology (SIO) evidence-based guideline for the use of integrative therapies after breast cancer treatment, stating that ginger could be considered as an addition to standard antiemetic drugs to control nausea and vomiting during chemotherapy [42].
Acupuncture and related therapies — Several techniques have been used to stimulate the pericardium 6 (P6 or Neiguan) site, which is commonly thought to be useful in the management of CINV. These include manual stimulation with the insertion of fine needles (acupuncture), acupuncture using electrical stimulation (electroacupuncture), and noninvasive pressure on the skin over the P6 pressure point (ie, acupressure).
Multiple trials have explored the benefits of acupuncture and acupressure for control of CINV [43-47]. Unfortunately, interpretation of the results of randomized trials is hampered by a high risk of bias in most studies and a lack of a control group undergoing a sham procedure in most, lack of standardization of treatment methods, and comparison groups that do not reflect modern antiemetic therapy. A year 2013 systematic review of acupuncture in cancer care included 11 randomized trials in which nausea and vomiting were assessed; eight were considered to have a high risk of bias [48]. Only one trial [43] had a low risk of bias and demonstrated a short-term benefit for electroacupuncture after chemotherapy for breast cancer. The authors concluded that, based upon the single positive study with a low risk of bias, acupuncture could be considered an appropriate adjunctive treatment for management of CINV but that additional studies were needed.
Even if there are benefits, they are likely to be modest:
●In one multicenter randomized sham-controlled trial, the addition of acupuncture to standard antiemetics for prevention of CINV did not improve the proportion of patients with a complete control of CINV at any time point (from day 1 through day 21), but it did modestly reduce the severity of both nausea and vomiting [49]. Treatment was overall well-tolerated, and there were no adverse events in either group in the study.
●In another trial, in which 500 patients receiving chemotherapy were randomly assigned to acupressure wrist bands, a sham acupressure control group, or conventional antiemetic care, there were no statistically significant differences among all three arms as regards to control of nausea, vomiting, or quality of life, although the median nausea scores for the four cycles of chemotherapy were somewhat lower in both the real and sham acupressure groups [46]. Furthermore, qualitatively, patients perceived the wristbands (both real and sham) to be as effective and helpful in the management of their chemotherapy-related nausea. These data suggest a strong placebo-effect, as has been seen in other trials utilizing these approaches in a variety of settings. (See "Acupuncture", section on 'Difficulties in research'.)
Consensus-based guidelines are discordant:
●Updated 2020 antiemetic guidelines from ASCO state that the evidence is insufficient for a recommendation for or against use of acupuncture/acupressure to prevent CINV [3].
●On the other hand, in the 2018 endorsement of the SIO guideline for the use of integrative therapies after breast cancer treatment, ASCO stated that acupressure and electroacupuncture could each be considered as an addition to antiemetic drugs to control nausea and vomiting during chemotherapy [42].
●NCCN guidelines suggest consideration of acupuncture/acupressure as an alternative treatment approach for anticipatory CINV only [4].
Other nonpharmacologic complementary/integrative medicine strategies — Findings from randomized controlled trials of reasonable quality provide limited support for several nonpharmacologic complementary/integrative therapy approaches to reduce CINV, including cognitive distraction (eg, playing video games during treatment), systematic desensitization (a cognitive approach using visualization and learned relaxation techniques), exercise, massage, hypnosis, progressive muscle relaxation, yoga, and transcutaneous electrical nerve stimulation [50-55]. (See "Complementary and alternative therapies for cancer".)
Updated 2020 guidelines from ASCO and the joint ASCO/SIO guideline on integrative therapies for patients with breast cancer both state that the evidence is insufficient for a recommendation for or against use of any of these complementary/integrative therapies to prevent or treat CINV [3,42,56].
Managing subsequent cycles of chemotherapy — Once the breakthrough emesis has been controlled, attention must be paid to modifying the prophylactic regimen to be used for subsequent chemotherapy courses, if continuation of the same regimen is planned.
The majority of patients who have breakthrough emesis have derived some benefit from the original antiemetic regimen employed. Thus, the original antiemetic regimens should usually be retained, and other agents added.
Options for modifying the prophylactic antiemetic regimen include:
●If the chemotherapy regimen was categorized as moderate risk (eg, a non-carboplatin-containing regimen), the prophylactic regimen can be adjusted to one that is typically used for a higher risk group (ie, with the addition of a NK1R antagonist) (table 1). (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Recommendations for specific groups'.)
●If it was not given initially, olanzapine can be added to the prophylactic regimen. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)
●If the patient previously received olanzapine, the addition of an agent from a different drug class is reasonable and supported by NCCN guidelines [4]. The choice of agent should be based on assessment of the current prevention strategies used. Some patients may require several agents utilizing differing mechanisms of action.
Options include lorazepam or alprazolam, or a dopaminergic antagonist (eg, prochlorperazine, thiethylperazine, haloperidol), or substituting high-dose intravenous metoclopramide for the 5-HT3 antagonist [3,57]. (See 'Alternative conventional antiemetics' above.)
●Another alternative is to switch to a different 5-HT3 antagonist since there may be incomplete cross-resistance between agents [58-61]. This approach was tested in a double-blind trial in which patients who failed ondansetron plus dexamethasone in the first 24 hours following highly emetogenic chemotherapy were randomly assigned to continue the same treatment or switch to granisetron plus dexamethasone. There was a significantly higher rate of complete protection from emesis in the patients who switched to granisetron (47 versus 5 percent) [58].
●If anxiety is a major factor in the refractory CINV, the addition of a benzodiazepine may be particularly helpful. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Anticipatory emesis'.)
●If patients desire nonpharmacologic therapy, a trial of acupuncture/acupressure is reasonable although benefits appear modest, at best. (See 'Acupuncture and related therapies' above.)
●If patients desire a trial of a cannabinoid, such an approach is also reasonable. One placebo-controlled randomized phase II trial that used a crossover design examined the efficacy of adding an oral mixture of THC plus CBD to dexamethasone, a 5HT3 receptor antagonist, and an NK1R antagonist for subsequent cycles of chemotherapy in 81 patients with poorly controlled emesis after the first cycle [62]. Efficacy was modest (complete response rates improved from 14 to 25 percent, but 72 percent of the patients in the cannabinoid arm required rescue with conventional antiemetics, and 31 percent still vomited), and 31 percent experienced moderate or severe cannabis-related adverse effects, including sedation, dizziness, and disorientation. Despite this, patient preference after the crossover phase overwhelmingly favored the cannabinoid (83 versus 15 percent). A randomized phase III trial is planned. (See 'Cannabinoids and medical marijuana' above.)
As noted above, we do not offer medical marijuana or CBD oil for either prophylaxis or treatment of CINV.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chemotherapy-induced nausea and vomiting in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Nausea and vomiting with cancer treatment (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Evaluation – For patients presenting with poorly controlled or breakthrough chemotherapy-induced nausea and vomiting (CINV), clinicians should reevaluate disease status, concurrent illnesses and medications, the predicted emetic risk of the chemotherapy regimen, and ascertain that the appropriate and best prophylactic regimen was administered for that regimen. (See 'Initial evaluation' above.)
●Antiemetic treatment – If an otherwise treatable cause is not identified, adding an appropriate antiemetic therapy to the initial prophylactic regimen is appropriate.
For most patients we suggest olanzapine rather than a different rescue antiemetic, in addition to continuing the standard antiemetic regimen (Grade 2C). The use of a 5 mg rather than 10 mg dosing regimen may reduce treatment-related sedation. (See 'Olanzapine' above.)
Alternatives to olanzapine are appropriate, particularly if the patient had been previously treated with olanzapine. Options include a neurokinin-1 receptor antagonist, lorazepam or alprazolam, a dopaminergic antagonist (eg, prochlorperazine, thiethylperazine, haloperidol), or an alternative type of 5-hydroxytryptamine (5-HT3) antagonist than was administered initially. (See 'Alternative conventional antiemetics' above.)
●Role of other therapies – We do not offer use of medical marijuana or cannabidiol (CBD) oil for prevention or treatment of CINV. However, cannabinoids such as dronabinol and nabilone (where available) are an option for rescue antiemetics; their modest efficacy must be counterbalanced by the risk for side effects, particularly in older adults. (See 'Cannabinoids and medical marijuana' above.)
For patients with CINV despite an adequate prophylactic regimen, there is insufficient evidence for a recommendation either for or against the use of ginger supplementation, acupuncture/acupressure, or other complementary therapies. However, these modalities have low potential for harm, and a trial of these approaches is reasonable for patients who desire it. (See 'Complementary therapies' above.)
●Subsequent cycles of chemotherapy – Once the breakthrough emesis has been controlled, future prophylactic regimens for subsequent chemotherapy courses should be modified if the same chemotherapy regimen is to be continued. Several strategies may be considered, based upon clinician and patient preference, and are outlined above. (See 'Managing subsequent cycles of chemotherapy' above.)
