|Year : 2016 | Volume
| Issue : 3 | Page : 454-456
Weekly cisplatin (30–40 mg/m2) as radiosensitizer: Is it high or moderate emetic agent?
A Karpe, VM Patil, A Joshi, V Noronha, S Gupta, A Ramaswamy, A Sahu, V Doshi, T Gupta, S Rath, S Banavali, K Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||24-Feb-2017|
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
PURPOSE: The American Society of Clinical Oncology (ASCO) guideline recommends a high antiemetic prophylaxis for any dose of cisplatin. This hypothesis was tested by us in this analysis of solid tumor patients who received weekly cisplatin as a radiosensitizer in a dose range of 30–40 mg/m2. METHODS: This was a retrospective analysis of 181 solid tumor patients who received weekly cisplatin (in the dose range of 30–40 mg/m2) as a radiosensitizer between July 2015 and August 2015. The antiemetic prophylaxis schedule provided was classified as optimal (if a high antiemetic prophylaxis was provided) or suboptimal (if a nonhigh antiemetic prophylaxis was provided). The incidence of acute, delayed and breakthrough vomiting after chemotherapy was noted. SPSS version 20 was used for analysis. Fisher's exact test was used to determine the association between antiemetic schedule (suboptimal vs. optimal) and postchemotherapy emesis. RESULTS: In the present study, of 181 patients, only 25 patients (13.8%) received optimal antiemetic prophylaxis while the remaining 156 (86.2%) received suboptimal prophylaxis. In the cohort of patients with suboptimal prophylaxis, dexamethasone was omitted in all patients (100%) while NK receptor antagonist was omitted in 76 patients (48.7%). The rate of vomiting was lower in patients receiving optimal prophylaxis as compared to that in patients receiving suboptimal prophylaxis (12% vs. 39.75%; P - 0.005). CONCLUSION: Omission of dexamethasone followed by aprepitant was the main reason for suboptimal prophylaxis. High antiemetic prophylaxis in accordance with ASCO guidelines overall decreased the risk of emesis in patients receiving CTRT with weekly cisplatin in the dose range of 30–40 mg/m2.
Keywords: American Society of Clinical Oncology, antiemetic, chemotherapy-induced nausea and vomiting, weekly cisplatin
|How to cite this article:|
Karpe A, Patil V, Joshi A, Noronha V, Gupta S, Ramaswamy A, Sahu A, Doshi V, Gupta T, Rath S, Banavali S, Prabhash K. Weekly cisplatin (30–40 mg/m2) as radiosensitizer: Is it high or moderate emetic agent?. Indian J Cancer 2016;53:454-6
|How to cite this URL:|
Karpe A, Patil V, Joshi A, Noronha V, Gupta S, Ramaswamy A, Sahu A, Doshi V, Gupta T, Rath S, Banavali S, Prabhash K. Weekly cisplatin (30–40 mg/m2) as radiosensitizer: Is it high or moderate emetic agent?. Indian J Cancer [serial online] 2016 [cited 2017 Mar 30];53:454-6. Available from: http://www.indianjcancer.com/text.asp?2016/53/3/454/200666
| » Introduction|| |
Cisplatin is a commonly used antineoplastic agent with a considerable emetogenic potential. The emetogenic potential of cisplatin was considered a function of its dose. Cisplatin in a dose ≥50 mg/m 2 was considered as having high emetogenic potential and cisplatin in a dose of <50 mg/m 2 was considered as having moderate emetogenic potential. However, recent National Comprehensive Cancer Network and the European Society for Medical Oncology guidelines consider any dose of cisplatin as having a high emetogenic potential. High antiemetic prophylaxis regimen warrants administration of an NK-1 receptor antagonist, 5-HT3 receptor antagonist, and dexamethasone on day 1 and NK-1 receptor antagonist and dexamethasone on subsequent 2–3 days postchemotherapy administration.
One of the common indications of cisplatin in oncology is as a radiosensitizer., Both 3 weekly and weekly schedules are used for radiosensitization in head and neck cancers and cervical cancers, with a weekly dose range of 30–40 mg/m 2. Whether this dose range should be considered as having a high emetogenic potential is debatable. In a recent survey done in practicing oncologist by the authors, 46.9% of oncologists prescribed a moderate antiemetic prophylaxis along with weekly cisplatin (unpublished data). This study was planned to understand the antiemetic prophylaxis pattern at our institute in patients receiving cisplatin for radiosensitization and to study the impact of high antiemetic prophylaxis on prevention of vomiting.
| » Methods|| |
The study was conducted with the hypothesis that any dose of cisplatin has high emetogenic potential and should be offered high antiemetic prophylaxis as per the American Society of Clinical Oncology (ASCO) guidelines. This is a retrospective analysis of solid tumor patients who were treated with radiotherapy with concurrent cisplatin (30–40 mg/m 2) as radiosensitizer at our institute from July 2015 to August 2015. The Institutional Ethics Committee (IEC) III of Tata Memorial Center had approved the protocol. IEC granted a waiver of the requirement for informed consent as this is retrospective analysis.
One hundred and eighty-one solid tumor patients receiving weekly cisplatin along with radiotherapy from July 2015 to August 2015 were selected for the present study. From electronic medical records (EMRs) prescriptions were selected and subjected to following criteria.
- Patients receiving radiotherapy for solid tumors
- Age ≥16 years
- Weekly cisplatin (30–40 mg/m 2) as concurrent chemotherapy.
The prescription details of antiemetics were obtained from EMR. The antiemetic prophylaxis received was classified as:
- Optimal: The antiemetic prophylaxis (antiemetics, dose, and duration) given according to ASCO antiemetic guideline (for high emetogenic potential chemotherapy) with or without any additional antiemetics
- Suboptimal: The antiemetic prophylaxis was not given according to ASCO antiemetic guideline (for high emetogenic potential chemotherapy). Either antiemetics were omitted totally or not used on all recommended days or recommended duration or in lower than recommended doses.
To identify patients who had chemotherapy-induced nausea and vomiting (CINV), EMR of all patients in the study was reviewed. Postchemotherapy vomitings were considered CINV if the following criteria were met:
- Vomiting within 5 days postchemotherapy and
- No other identifiable causes of vomiting such as brain metastasis.
Vomiting further classified as acute (within 24 h of chemotherapy) or delayed (between 24 and 120 h after chemotherapy).
SPSS Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. was used for statistical analysis. Descriptive statistics were performed. Fisher's test was used to determine the impact of optimal versus suboptimal antiemetic prophylaxis on the rate of emesis, rate of emergency visits for emesis, and rate of hospitalization done due to emesis. One-sided P value of 0.05 was considered as statistically significant.
| » Results|| |
Baseline demographics can be seen in [Table 1]. A total 181 patients were included in the present study. Median age of study population was 47 years (interquartile range - 17–72 years). Out of these 181 patients, 71 (39.22%) were males while 110 (60.78%) were females. Distribution of solid tumors in patients who had received radiotherapy with weekly cisplatin (30–40 mg/m 2) as radiosensitizer in the present study is given in [Table 1].
Out of 181 patients, 25 patients (13.8%) received optimal antiemetic prophylaxis according to ASCO guidelines while 156 (86.2%) patients received suboptimal prophylaxis. In patients who received suboptimal prophylaxis, 77 patients (49.3%, n = 156) had one drug omitted while 79 (51.7%, n = 156) had two drugs omitted from the recommended regimen by ASCO [Table 2]. Dexamethasone was omitted in all 156 (100%) patients. It was omitted in delayed schedule (day 2–day 4 of dexamethasone) in 77 patients (49.3%). NK receptor antagonist was omitted in 76 patients (48.7%).
Impact of optimal versus suboptimal antiemetic prophylaxis
In five patients, data regarding emesis was missing. Hence, 176 patients were available for evaluation. Patient receiving optimal antiemetic prophylaxis had decreased rates of emesis (12%, three patients) as compared to suboptimal prophylaxis (39.75%, sixty patients) (P - 0.005). Acute vomiting was seen in 19 patients (12.6%) in suboptimal prophylaxis group while in 1 patient (4%) in optimal group and this difference was statistically significant (P - 0.0184). Similarly, delayed vomiting was seen in 44 patients (29.1%) in suboptimal prophylaxis group, and in 2 patients (8%) in optimal group, with difference being statistically significant as well (P - 0.017). Sixteen patients (10.6%) in suboptimal prophylaxis required emergency visits as compared to one patient (4%) with optimal prophylaxis for emesis (P - 0.267). Hospitalization was indicated in 13 cases (8.6%) in the suboptimal prophylaxis cohort versus 1 case (4%) in optimal prophylaxis group cohort (P - 0.378). On binary logistic regression analysis, supoptimal antiemetic schedule (P - 0.004) and female gender (0.013) were the only factor predicting for emesis.
| » Discussion|| |
The occurrence of emesis during chemotherapy is a multifactorial phenomenon. It depends on the chemotherapy administered, age of the patient, gender, emesis with previously administered chemotherapy, and also on concurrent therapies such as radiation. Radiation itself is emetogenic. Administration of radiation in large fields, especially to the abdomen is associated with higher risk of emesis., While a large body of research exists with regard to antiemetics in the prevention of CINV with chemotherapy, very limited data are available in the concurrent chemoradiation setting.
Concurrent chemoradiation is a curative treatment commonly utilized in locally advanced head and neck cancers and in uterine cervical carcinomas. Radiation at both these sites itself is emetogenic. Weekly concurrent cisplatin is a common regimen utilized for radiosenstization. Due to the weekly schedule, treating oncologists have concerns regarding the use of high antiemetic prophylaxis. A high antiemetic prophylaxis warrants administration of 12 mg dexa on day 1 and 8 mg dexa from day 2 to 4. Administration of potent steroid like dexamethasone for 5–7 weeks period is likely to predispose patients to steroid-related immunosuppression, gastritis, hyperglycemia, mood changes, and other side effects. Besides adverse events related to steroid usage, additional antiemetic prophylaxis in the form of aprepitant also has added cost considerations. This potentially leads to 46.9% of oncologists prescribing a moderate antiemetic prophylaxis (unpublished data). In this study, high antiemetic prophylaxis was used in only 13.8%.
Use of high antiemetic prophylaxis as shown in the present study, expectedly, is associated with a lower rate of emesis, emergency visits, and hospitalization. Multiple studies in combination chemotherapy and in single agent chemotherapy requiring high antiemetic prophylaxis have shown that suboptimal prophylaxis is associated with high rates of emesis.,, The result is also supported by a randomized study in patients with cervical cancer, which was reported after our study was initiated. The use of high antiemetic prophylaxis consisting of fosaprepitant, palonosetron, and steroids was associated with a significant improvement in emesis control rate. While confounding factors such as female gender, large pelvic fields (>10 cm × 10 cm), and different dosages per se (as seen in the trial) are associated with higher incidence of emesis and comparison to a predominantly male head and neck cancer population (as in the present study) may not be completely accurate, the results in our study seem to be in general agreement with the trial results. In addition to the above, our results also clarify that irrespective of the site of radiation, gender, and dose of cisplatin (30 or 40 mg/m 2), antiemetic prophylaxis for high-risk emetogenic group is required.
| » Conclusion|| |
In our study, the omission of dexamethasone and NK receptor antagonists was the main reason for suboptimal prophylaxis. It appears that emetogenic potential of cisplatin is independent of its dose. Hence, as per ASCO guideline, all dosing schedules of cisplatin should be offered antiemetic prophylaxis for high emetogenic risk. Optimal prophylaxis had overall decreased rates of CINV (statistically significant) as well as rates of emergency visits and hospitalization, thus reducing the overall health-care burden.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, et al
. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-9.
Suzuki S, Izumi K, Enokida T, Yajima Y, Kobayashi T, Ishiki H, et al
. Evaluation of nausea and vomiting in radiation plus concurrent weekly cisplatin (weekly CDDP+RT) without prophylactic aprepitant in head and neck cancer. Tokeibu Gan 2013;39:391-5.
Hesketh PJ, Bohlke K, Lyman GH, Basch E, Chesney M, Clark-Snow RA, et al.
Antiemetics: American Society of Clinical Oncology Focused Guideline Update. J Clin Oncol 2016;34:381-6.
Candelaria M, Garcia-Arias A, Cetina L, Dueñas-Gonzalez A. Radiosensitizers in cervical cancer. Cisplatin and beyond. Radiat Oncol 2006;1:15.
Strojan P, Vermorken JB, Beitler JJ, Saba NF, Haigentz M Jr., Bossi P, et al.
Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review. Head Neck 2016;38 Suppl 1:E2151-8.
Gupta PK, Lal P, Bajpai R, Goel A, Yadav R, Verma M, et al.
Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer. South Asian J Cancer 2016;5:80-4.
Scarantino CW, Ornitz RD, Hoffman LG, Anderson RF Jr. Radiation-induced emesis: Effects of ondansetron. Semin Oncol 1992;19 6 Suppl 15:38-43.
Maranzano E. Radiation-induced emesis: A problem with many open questions. Tumori 2001;87:213-8.
Hilarius DL, Kloeg PH, van der Wall E, van den Heuvel JJ, Gundy CM, Aaronson NK. Chemotherapy-induced nausea and vomiting in daily clinical practice: A community hospital-based study. Support Care Cancer 2012;20:107-17.
Aseeri M, Mukhtar A, Al Khansa S, Elimam N, Jastaniah W. A retrospective review of antiemetic use for chemotherapy-induced nausea and vomiting in pediatric oncology patients at a tertiary care center. J Oncol Pharm Pract 2013;19:138-44.
Yu S, Burke TA, Chan A, Kim HK, Hsieh RK, Hu X, et al. Antiemetic therapy in Asia Pacific countries for patients receiving moderately and highly emetogenic chemotherapy – A descriptive analysis of practice patterns, antiemetic quality of care, and use of antiemetic guidelines. Support Care Cancer 2015;23:273-82.
Ruhlmann CH, Christensen TB, Dohn LH, Paludan M, Rønnengart E, Halekoh U, et al.
Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): A multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol 2016;17:509-18.
[Table 1], [Table 2]