Demographic profile and clinical characteristics of patients with breast cancer receiving highly emetogenic chemotherapy (n=71)

Of the 71 patients analyzed, 21 patients received a combination of Adriamycin and cyclophosphamide and 50 patients received epirubicin along with cyclophosphamide [Table 2].

Highly emetogenic chemotherapy regimens prescribed in patients with breast cancer, along with mean doses prescribed (n=71)

All patients (n = 71) were prescribed premedication in with at combination of ondansetron and dexamethasone intravenously at a dose of 8 mg each or a dose of 16 mg each. Along with this, in the first cycle, 48 patients were prescribed an aprepitant kit, given as 125 mg orally on the 1st day of chemotherapy and followed by a maintenance dose of 80 mg orally on days 2 and 3. The antiemetic regimens prescribed were as per the treating physician's discretion and were modified in subsequent cycles based on the feedback given by the patient as per her experience in the prior cycle. Thus, six patients in the second cycle were escalated to a regimen containing aprepitant and four more in the third cycle were prescribed additional aprepitant [Table 3]. In all cycles, the patients were given ondansetron three times a day for 5 days, as well as rescue medication in case the patient experienced more nausea or increased frequency of vomiting episodes. In case of severe nausea or vomiting, patients were prescribed injection granisetron 3 mg intravenously.

Antiemetic regimens prescribed in patients with breast cancer, along with doses prescribed (n=71)

None of the patients in the first cycle required rescue with injection granisetron. Two patients in the second cycle and one patient in the third cycle received granisetron as rescue medication.

The mean scores for the intensity of nausea as per the VAS were higher for the patients who were prescribed ondansetron and dexamethasone alone as compared to patients prescribed Aprepitant plus ondansetron and dexamethasone. The VAS scores were highly significant in the triple-drug regimen at 6 h, 24 h, and 48 h postchemotherapy as compared to the two-drug regimen [Table 4a]. In the second cycle and third cycles, the mean VAS scores were significantly lower at 6 h, 24 h, and 48 h postchemotherapy for the patients receiving aprepitant as part of the antiemetic regimen [Table 4b] and [Table 4c].

Comparison of visual analog scale score for intensity of nausea in cycle 1 in patients receiving antiemetic regimens for highly emetogenic chemotherapy (n=71)

Comparison of visual analog scale score for intensity of nausea in cycle 2 in patients receiving antiemetic regimens for highly emetogenic chemotherapy (n=71)

Comparison of visual analog scale score for intensity of nausea in cycle 3 in patients receiving antiemetic regimens for highly emetogenic chemotherapy (n=71)

In cycles 2 and 3, patients in both the regimens experienced nausea at 0 h of chemotherapy, i.e., anticipatory nausea; however, we did not observe a statistically significant difference in the extent of anticipatory nausea between the two regimens [Figure 1].

Comparison of frequency of no emesis in the acute, delayed, and overall phase in patients receiving antiemetic regimens for highly emetogenic chemotherapy (n=71)

Further, in our study, none of the patients prescribed either antiemetic regimen reported a complete control of symptoms, i.e., no nausea, no emesis, and no need for rescue medication across any of the cycles of chemotherapy.

In our study, five patients had adverse drug reactions which were possibly linked to the antiemetic regimens used. Three patients reported urticaria after injection ondansetron and were prescribed antihistaminic drugs for the same. Two patients reported constipation, which likely could be due to ondansetron, and were treated with stool softeners. None of the patients reported any serious adverse effects linked to the antiemetic regimens.

Discussion

The impact of the diagnosis and treatment of cancer is not only on the physical domain of well-being but also on the emotional, social, and spiritual aspects of a person.[8] Chemotherapy as such, by default, results in definite adverse effects as well as long-term sequelae such as neutropenia, anemia, and bone marrow suppression along with gastrointestinal adverse effects like nausea and vomiting, mucositis, and diarrhea.[9] All these adverse effects may translate to noncompliance to the treatment protocol or a higher cost of treatment to be paid by the patient.[10]

Nausea and vomiting is a very distressing side effect induced by chemotherapy for solid tumors which not only occurs very commonly in almost 70%–80% individuals but is also recurrent, that is, the patient will experience it during every subsequent cycle as well.[11] This can lead to nonadherence to the chemotherapeutic treatment, which can affect disease progression and recurrence. Further, nausea and vomiting has severe effects on the quality of life with impaired functioning, increased anxiety, or depression.[3]

Despite the best efforts to optimize the use of antiemetics, patients still experience nausea and/or vomiting during and after chemotherapy, especially with HEC. The efficacy of different antiemetics can vary according to various factors such as patient characteristics, the type of chemotherapy received as well as the site of cancer tumors.[12] The addition of NK1 receptor antagonists to the antiemetic regimens has yielded a better armament for tackling CINV.

The most frequently used antiemetic regimen in our study was a combination of NK1 receptor antagonist, aprepitant along with 5-HT3 receptor antagonist, ondansetron and dexamethasone, followed by ondansetron with dexamethasone in all the three cycles of solid tumors.

The NK1 receptor antagonist prescribed in our study was a 3-day regimen of oral aprepitant. Along with this, patients were given premedication either with 8 mg or 16 mg each of ondansetron and dexamethasone, both given intravenously. A maintenance dose of oral ondansetron was also prescribed thrice a day for 5 days and to be taken as per the requirement as rescue medication. All doses prescribed were as per the treating physician's empirically based discretion.

We observed a deviation in the doses used for antiemetic drugs as compared to internationally used regimens. In a study done by Dranitsaris et al., patients were prescribed either a combination of ondansetron and dexamethasone added to aprepitant or only a regimen of ondansetron and dexamethasone. However, the regimen varied from our study as patients were premedicated with dexamethasone 12 mg given intravenously and ondansetron 8 mg given orally, repeated after 8 h.[13] A variation in the dosage regimen has reflected in the incomplete control of nausea and vomiting with the antiemetic regimens used in our study.

The patients reported anticipatory nausea as observed on the VAS in cycle 2 and cycle 3 at 0 h. The anticipatory nausea was lesser in the aprepitant containing regimen as compared to the ondansetron and dexamethasone containing regimen.

In a study done by Molassiotis et al., they explored the incidence of anticipatory nausea in patients in successive chemotherapy cycles. They concluded that in patients receiving the second and third cycles of chemotherapy, there was a significant increase in patients presenting with anticipatory nausea, similar to our results.[14]

Profoundly symmetrical graphs are obtained when comparing VAS scores in the three cycles. There is a very minor difference in the intensity of nausea between the three cycles; thus, repeated exposure has not significantly reduced the susceptibility of the patients to experience nausea.

In our study, in the acute phase of cancer chemotherapy, the incidence of no emesis was better with the three-drug combination, containing aprepitant as compared to the two-drug regimen over the acute, delayed as well as overall phase. Similar results were observed across the second and third cycles of chemotherapy as well confirming the results of a study by Hilarius et al. in their investigation in a community hospital in daily practice.[15] In their study, they observed that the control of emesis in the delayed phase did not vastly differ between the regimens which contained aprepitant as compared to the regimen without aprepitant. In contrast, we observed a marked difference in the delayed phase, an effect that may be explained by the longer action of aprepitant which persists beyond the acute phase.

Present guidelines for patients receiving HEC suggest the use of an NK 1 receptor antagonist along with premedication with ondansetron and dexamethasone for the adequate control of CINV, as well as additional prescription of olanzapine and dexamethasone on the subsequent days.[5]

The primary reason for inadequate prescription of the NK1 receptor antagonist was probably a lack of sensitization of physicians, as well as a lack of awareness of the latest recommendations. Due to inadequate knowledge of the advantages of olanzapine or dexamethasone, they were possibly not included in the antiemetic regimen of the patients in the maintenance dose as suggested by international guidelines. A suboptimal utilization of aprepitant as a prophylactic drug is most likely due to the socioeconomic constraints of the patients. The addition of aprepitant increases the cost incurred by the patient drastically as compared to a prescription of ondansetron–dexamethasone alone. In a resource-poor setting like India, a due consideration has to be made for the ability of the patients to afford the additional cost of aprepitant or other drugs of the same class.[16]

Some of our study limitations were inadequate sample size, as well as a possible bias due to the subjective nature of nausea. As our study sample consisted of only breast cancer patients, the assessment for other cancers may be inadequate. Further, a cost analysis can be performed to assess the economic impact of the control of CINV. This study can further be expanded to include different emetogenicity of chemotherapeutic regimens and different regimens of antiemetic drugs as well as can be investigated by the specific site of cancer to get a better impression of the extent of CINV.

Conclusion

For any patient being treated for cancer, the occurrence of CINV is a disturbing and immediate adverse effect that drastically effects the life of the patient. In our study, a statistically significant difference in VAS scores between the regimens was observed. In addition, we observed that with a combination of aprepitant, ondansetron, and dexamethasone, the control of CINV was better as compared to a regimen without aprepitant. Thus, more patients reported a better response, in terms of no emesis when prescribed aprepitant. Still, a lot needs to be done to achieve a complete cure in our setting. There is a constant need for constructing an evidence-based regimen that can be uniformly applied to optimize the efforts to control and treat this disturbing adverse effect of chemotherapy. Due consideration can be made to try and maximize the effectiveness of the antiemetic regimen to ensure patient compliance to chemotherapy.

Acknowledgments

The authors would like to sincerely acknowledge the contribution of Himalayan Institute of Medical Sciences and Cancer Research Institute, Himalayan Hospital Dehradun. The authors humbly thank the guidance provided by the faculty and staff of the Department of Pharmacology and Department of Medicine, HIMS, Dehradun. We would like to extend our gratitude to all colleagues for the support and encouragement.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Received: 27 April 2020

Accepted: 22 August 2020

Article published online:
14 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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