Abstract

Introduction

Cancer is one of the leading causes of morbidity and mortality worldwide. According to world cancer fund, one-third of cancer cases in economically developed countries are due to physical inactivity, excess alcohol consumption, smoking, obesity, and poor nutrition. In case of developing countries like India, life style changes and environmental factors are major causes of cancer. According to the American Cancer Society, about 1688,780 new cancer cases were expected to be diagnosed and 600,920 cancer deaths in 2017.[1] Based on cancer scenario in India the incidence of cancer is 70–90/100,000 population and prevalence of cancer is found to be around 2.5 million with over 800,000 new cases and 550,000 deaths occurring each year. About 6% of all deaths in India are due to cancers, which contribute to 8% of global cancer mortality.[2]

Chemotherapy is the main-stay of treatment in patients with advanced malignant disease, which is incurable by local surgery or radiotherapy.[3] Although there are different targeted therapies have been approved for cancer therapy, these therapies may compliment rather than replace chemotherapy. However, chemotherapy improves survival it has its own toxicity and side effects. The most common of which are nausea and vomiting, diarrhea, alopecia, mucositis, and myelosuppression. Among which nausea and vomiting are the frequently observed side effect of chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) also leads to fatigue, muscle strain, esophageal tears, metabolic imbalance, lowered cognitive function, and increased anxiety or depression.[4]

Three different types of CINV have been identified; namely, Acute, delayed, and anticipatory. Acute emesis begins within 1–2 h of treatment and peaks in the first 4–6 h. Delayed emesis occurs more than 24 h after treatment, peaks at 48–72 h and then subsides over 2–3 days.[5] Anticipatory emesis occurs in patients who have developed significant CINV during previous cycles of therapy. Acute CINV is often associated with an increase in plasma serotonin concentrations for the most emetogenic agent while delayed and anticipatory vomiting seem to be mediated by serotonin independent pathways.[5] The patient risk for CINV is influenced by the emetogenicity of the chemotherapeutic agent.

The chemotherapeutic agents are classified into four emetic risk categories. It includes high (>90% of frequency of emesis), moderate (30%–90%), low (10%–30%), and minimal (<10 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686978/#ref5" rid="ref5" class=" bibr popnode" role="button" aria-expanded="false" aria-haspopup="true" xss=removed>5] The guidelines to prevent CINV includes the American Society of Clinical Oncology,[6] the Multinational Association for Supportive Care in Cancer[7] and National Comprehensive Cancer Network (NCCN). The principles of emesis control for cancer patient from NCCN include; (1) the goal of treatment is to prevent nausea/vomiting. (2) The risk period for chemotherapy induced nausea and vomiting with highly emetogenic chemotherapy (HEC) and moderate emetogenic chemotherapy (MEC) is at least 3 days and patients should be protected for the entire risk period. (3) Oral and intravenous (IV) 5-HT3 antagonists have equivalent efficacy when used at the appropriate doses. (4) choice of antiemetic(s) used should be based on emetic risk of chemotherapy, a patient's prior antiemetic experience, and other patient factors; and (5) for multi-drug regimens, select antiemetic therapy based on the drug with the HEC and consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.

Although there are many observational studies to implement antiemesis guidelines in practice, the adherence to guidelines in preventing CINV still remains as a main issue. The current study helps to evaluate the utilization of antiemetics in CINV, to assess the emetogenicity of chemotherapeutic agents and also the incidence of CINV.

Methods

It was a prospective study carried out in patients who were admitted in the Department of Oncology at a Teaching Hospital. The study was conducted from October 2016 to March 2017. Hospitalized patients above 18 years of either gender receiving chemotherapy was included in the study and patients with brain metastases, radiation-induced nausea and vomiting were excluded from the study. This study was approved by the Central Ethics Committee of the institution (enclosed), and informed consent form was obtained from all the participants.

A suitable data collection form was designed to collect and document data. It had a provision for recording information related to demographic details of the patient, cancer/treatment informations. A separate section was provided to record the details of the medications the patients were on, at the time and during the study.

To find out the incidence of chemotherapy-induced nausea and vomiting morrow assessment of nausea and emesis (MANE) form[8] was used. The MANE form involved questionnaire about the incidence of CINV, whether before or after the last chemotherapy treatment, the duration that patient experiences CINV in hours, and the description of CINV at its worst (very mild, mild, moderate, severe, very severe, and intolerable), the MANE form also involved questionnaire about the usefulness of antiemetic taking by patients which scored as (very useful, somewhat useful, works a little, or does not seem to help).

The chemotherapeutic regimens given were assessed based on their emetogenic potential and then classified them into high, moderate, low, and minimal using the standard NCCN guidelines.

Results

The questionnaire was completed for 200 cancer patients receiving chemotherapy. Among 200 cancer patients participated in the study, majority 112 (56%) were found to be female and remaining 88 (44%) were male. The mean age was found to be 52 ± 11.65 (range: 18–83) years [Table 1].

Table 1

Discussion

The present study was conducted to study the utilization and evaluation of antiemetics used in CINV, and to evaluate the incidence of CINV. Two hundred patients were included in the study. The prevalence of cancer is found to be more in females than males. These results were consistent with previously published studies in oncology.[9,10,11] In this study, the majority of patients were in the age group of 48–57 years and the mean age was found to be 52 ± 11.65 years. This indicates that middle-aged people have higher incidence of cancer. These findings correlate with other studies.[9,12,13]

The study showed that the most common cancer was found to be breast cancer.[4,9] The most commonly used chemotherapy regimen was doxorubicin and cyclophosphamide combination followed by carboplatin and paclitaxel, epirubicin, oxaliplatin, and capecitabine. Cisplatin was the most commonly used individual chemotherapy drug.[14,15] The current study assessed the emetogenicity of chemotherapeutic agents according to the NCCN guideline. It revealed that most of the subjects received MEC followed by HEC,[13] in contrary, HEC was prescribed more than MEC regimen.[12]

The present study showed that the antiemetic therapy used was consistent with the standard guidelines of NCCN. For acute and delayed emesis, the updated NCCN guideline recommends triple therapy with an NK1-RA (aprepitant or fosaprepitant), 5HT3-RA (palonosetron or ondansetron or granisetron), and corticosteroid (dexamethasone) for HEC regimens. In MEC regimens, double therapy of 5HT3-RA and dexamethasone is recommended with or without NK1-RA. In the case of low emetogenic chemotherapy, a monotherapy of dexamethasone or Metoclopramide or 5HT3-RA is recommended, and no prophylaxis antiemetic therapy is recommended for minimal emetogenic chemotherapy. The results of prescribing pattern of antiemetic showed that most of the subjects are prescribed with Cap. aprepitant, dexamethasone IV, and palonosetron IV followed by dexamethasone IV and palonosetron IV. Almost all the patients received 5HT3-RA in combination with corticosteroid and NK1-RA. The results were consistent with other findings.[12,13]

The findings of the current study showed that there was good adherence to the current antiemesis guideline. However, the incidence of CINV was high. Among the study population, the incidence of nausea postchemotherapy was 69.5% of which 54% for acute and 15.5% for delayed. The incidence of vomiting postchemotherapy was 46%, in which 36.5% for acute and 14.5% for delayed. Whereas in other study, the incidence of nausea postchemotherapy was found to be 65.38% and vomiting 50%.[12]

The time of incidence of delayed (>24 h) nausea and vomiting after chemotherapy was 15.5% and 14.5%, respectively. The severity of nausea and vomiting incidence postchemotherapy was found to be mild (32.5%) and moderate (19.5%), respectively.[12] These results indicate that CINV remains a major problem for cancer patients receiving chemotherapy and it also gives an idea about the need for more efficient implementation of guidelines of antiemesis in the clinical practice.

Patient satisfaction regarding the usefulness of antiemetic medication shows that 70.5% patients reported that antiemetic medication was very useful, 21.5% reported somewhat useful, 3% works a little and 0.5% reported that does not seem to help. Whereas in other study,[12] they found that 38.46% of patients reported that antiemetic treatment used was not useful and 61.51% reported as useful.

The current study showed that incidence of nausea and vomiting prechemotherapy treatment was found to be 5.5% and 4%, respectively. The results were found to be in contrast that the incidence of CINV prechemotherapy treatment was zero.[12]

Conclusion

The study evaluated the utilization of antiemetics in CINV and the incidence of nausea and vomiting in cancer patients receiving chemotherapy. The majority of the patients received HEC and MEC regimen of chemotherapy and the most commonly prescribed antiemetic regimen was triple therapy (5HT3-RA, corticosteorid, and NK1-RA) followed by double therapy (5HT3-RA and Corticosteroid). In conclusion, the incidence of CINV was relatively high, and it indicates that more attention is needed for the treatment of both acute and delayed CINV. It also gives an idea for implementation of more efficient antiemesis guideline in the clinical practice.

Acknowledgment