|Year : 2014 | Volume
| Issue : 2 | Page : 222-224
Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study
Dattatreyo Chatterjee1, Somnath Roy2, Avijit Hazra3, Partha Dasgupta4, Subir Ganguly4, Anup Kumar Das1
1 Department of Pharmacology, R. G. Kar Medical College and Hospital, Kolkata, West Bengal, India
2 Department of Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
3 Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
4 Department of Radiotherapy, R. G. Kar Medical College and Hospital, Kolkata, West Bengal, India
|Date of Submission||29-Jul-2013|
|Date of Decision||21-Sep-2013|
|Date of Acceptance||18-Jan-2014|
|Date of Web Publication||24-Mar-2014|
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Objectives: Toxicity of cancer chemotherapy may be affected by nutritional status of patients which is reflected in the body mass index (BMI). We sought to assess whether the adverse drug reaction (ADR) profile of platinum-based chemotherapy varies with BMI status.
Materials and Methods: Adult patients of either sex, suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach, colon) and started on platinum-based chemotherapy as initial treatment were included. BMI at chemotherapy commencement was obtained from medical records. Events were recorded and graded as per Eastern Co-operative Oncology Group Common Toxicity Criteria-patients' complaints; clinically evident signs and laboratory reports were considered. Frequencies of individual adverse events were compared between low BMI (<18.5 kg/m 2 ) and satisfactory BMI groups. Similar comparisons were done for events with grades 2 or 3 severities.
Results: A total of 50 patients were observed over a 3-month period of whom 17 (34%) belonged to the low BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and paresthesia were the commonly observed ADRs. The frequencies of anemia (P = 0.152) and vomiting (P = 0.140) and severity of grades of nausea (P = 0.066), anemia (P = 0.120) and paresthesia (P = 0.128) showed a higher trend in the low BMI group though differences were not statistically significant. The frequencies of tinnitus (P = 0.021) and paresthesia overall (P = 0.036) were significantly higher in the low BMI group.
Conclusion: ADR profile of primary platinum-based chemotherapy appears to be partly influenced by BMI. This suggests the importance of maintaining adequate nutrition in patients and the need for greater vigilance in those with low BMI.
Keywords: Adverse drug reaction, body mass index, platinum-based chemotherapy, solid tumor
|How to cite this article:|
Chatterjee D, Roy S, Hazra A, Dasgupta P, Ganguly S, Das AK. Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study. Indian J Pharmacol 2014;46:222-4
|How to cite this URL:|
Chatterjee D, Roy S, Hazra A, Dasgupta P, Ganguly S, Das AK. Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study. Indian J Pharmacol [serial online] 2014 [cited 2020 Sep 22];46:222-4. Available from: http://www.ijp-online.com/text.asp?2014/46/2/222/129325
| » Introduction|| |
The majority of cytotoxic anticancer drugs have narrow therapeutic index and exhibit interindividual variation in toxicities. , Heterogeneity in body composition resulting from variation in nutritional status could be a potential source of variation in drug concentration and drug effects.  Available literature indicates a link between low body mass index (BMI) and chemotherapy related adverse drug reactions (ADR). ,, The oncology wing of tertiary care hospitals caters to patients of diverse socio-economic backgrounds. The nutritional status of a proportion of patients is not optimum and yet chemotherapy cannot be delayed because of the seriousness of their disease. We therefore sought to assess whether the toxicity profile of primary platinum-based chemotherapy varies with the nutritional status of the recipients as reflected in their BMI status.
| » Materials and Methods|| |
Permission was taken from the institutional ethics committee before commencement. Data was collected from 50 patients over a 3-month period from the day-care chemotherapy center and oncology wards of R. G. Kar Medical College and Hospital, Kolkata. Purposive sampling was done.
Adult patients of either sex, suffering from commonly encountered solid tumors (lung, stomach, head and neck, colon, gall bladder, ovary) who received at least one cycle of primary platinum-based chemotherapy were included. Obese patients and patients whose initial treatment was not chemotherapy were excluded. Data from each patient was captured after taking written informed consent.
Height and weight at the time of starting chemotherapy were obtained from medical records and BMI (kg/m 2 ) was calculated. The subjects under study were divided into two groups - with low BMI (<18.5 kg/m 2 )  and with satisfactory or normal BMI (18.5-25 kg/m 2 ) groups.
Only events with causality status of at least possible by World Health Organization-Uppsala Monitoring Center criteria were considered. All toxicities were recorded and graded as per the Eastern Co-operative Oncology Group Common Toxicity Criteria (ECOG-CTC).  Patients' complaints, clinically evident signs and laboratory reports were all considered.
Frequencies of individual adverse events were compared between groups by Fisher's exact probability test. Similar comparisons were done for individual toxicities with grades 2 or 3 severities as per ECOG-CTC. The relative risk (RR) and 95% confidence interval (CI) values have been presented where deemed relevant.
| » Results|| |
A total of 50 patients were observed of whom 17 (34%) belonged to the low BMI group. Malignancies of the lung (44%) and head and neck (12%) were the most common in our series. All patients were on primary platinum-based chemotherapy; 38 (76%) of them were receiving a cisplatin-based regimen, 7 (14%) were on carboplatin-based regimen and the remaining 5 (10%) were on oxaliplatin-based regimen.
All patients showed some toxicity. The commonly observed events were - alopecia (96%), anemia (90%), nausea (90%), vomiting (82%), paresthesia (54%), diarrhea (38%), stomatitis (38%) and ototoxicity (26%). Comparison of the ADR frequency in the two groups is depicted in [Table 1]. The frequency of ototoxicity, manifesting as tinnitus, was significantly higher in the low BMI group with RR of 3.11 (95% CI: 1.20-8.05). Paresthesia RR was 1.80 (95% CI: 1.12-2.9) in the low BMI compared with the normal BMI group.
|Table 1: Comparison of frequency of individual adverse reactions between two study groups|
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[Table 2] presents a similar comparison restricted to toxicity of grades 2 or 3 severities as per ECOG-CTC. There was no statistically significant difference between the two groups, through trend (P < 0.2) toward greater frequency in the low BMI group was noted for anemia, nausea and paresthesia.
|Table 2: Comparison of frequency of individual adverse reactions of grades 2 or 3 severity between two study groups|
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| » Discussion|| |
The present observational study has shown some differences in the ADR profile of primary platinum-based chemotherapy with respect to BMI status. A significantly higher incidence of tinnitus and paresthesia were noted in the low BMI individuals and a trend toward higher frequency in the same group was noted for multiple other ADRs, particularly more severe grade ADRs. The limited sample size could be the reason why these trends did not attain statistical significance, although clinically relevant.
A study by Antoun et al. indicated that renal cell carcinoma patients with low BMI and/or muscularity had high incidence of toxicity to sorafenib leading to dose reduction or stoppage of treatment.  Another study by Miya et al. indicated that BMI may be a factor related to chemotherapy-related toxicity even in patients receiving doses adjusted as per body surface area (BSA).  They found BMI to be inversely related to the fall in leukocyte and platelet counts during treatment with cisplatin and etoposide. Yet another study by Meyerhardt et al. on the impact of BMI on the outcomes and treatment-related toxicity in patients with stages II and III rectal cancer demonstrated an inverse relation between severe grades of 5-fluorouracil-based chemotherapy-induced neutropenia and BMI.  There were higher incidences of diarrhea, stomatitis and leukopenia among the underweight recipients. Ma et al. in their study have reported that a particular cohort of breast cancer patients receiving a combination of doxorubicin and cyclophosphamide experienced significantly higher grades of neutropenia compared with another cohort.  A lower BMI status in the former cohort was indicated as one of the important factors responsible for this difference. In a recent study Esfahani et al. explored the association between hospital outcome and nutritional status of acute leukemia patients undergoing induction chemotherapy and concluded that early nutritional assessment can help to identify patients who need nutritional support and This may contribute to less toxicity and better outcome.  Hasenberg et al. concluded, from a randomized controlled trial, that supplementation with parenteral nutrition slows weight loss, stabilizes body-composition and improves quality of life in patients with advanced colorectal cancer and furthermore, can reduce chemotherapy-related side effects. Our study also points to the possibility that toxicity of platinum-based chemotherapy regimens may be less severe if low BMI patients are identified and provided nutritional support. 
Doses of anticancer drugs are often individualized according to the BSA in order to minimize interindividual variations in therapeutic and toxic effects.  However, the results of the present study raises concerns similar to previous studies that in deciding dosing it is potentially important to also take into account, body weight or BMI. Available literature suggests that while dose modification based solely on BSA in acceptable, there is also need for detailed pharmacokinetic and pharmacodynamic study of combination chemotherapy to establish the ideal dose modification method for individual regimens. 
The present study has limitations. Being an observational study, a substantial proportion of data has been gathered based on patient recall rather than prospective data collection carried out under controlled clinical trial setting. As already stated, the limited number of patients could have curtailed statistical significance in case of some of the toxicities. Cycle-wise differences in adverse effects could not be assessed in this short study period. Furthermore, different regimens in different cancers can have different ADR profile and it would have been ideal if we restricted the observations to a particular type of cancer being treated with a particular regimen. However, we did not do this because of the relatively short duration of the study and for the sake of generalizability of the study findings. Rather than limiting to a particular regimen for a particular cancer, we focused on a group of drugs (platinum compounds) and a group of tumors (non-osteogenic solid tumors of the head-neck, lung or abdomen).
Despite these limitations, we can conclude that low BMI status is a risk factor for toxicity of platinum-based chemotherapy. Since nutrition is a major contributor to BMI, careful attention to nutrition of such patients in needed and clinicians need to be more vigilant for adverse events in this subgroup. Keeping the dearth of published data in Indian cancer patients in mind, it is worth exploring the influence of BMI status on toxicity profile of other types of chemotherapy regimens and in other types of malignancies.
| » References|| |
|1.||Prado CM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res 2007;13:3264-8. |
|2.||Antoun S, Baracos VE, Birdsell L, Escudier B, Sawyer MB. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol 2010;21:1594-8. |
|3.||Miya T, Goya T, Yanagida O, Nogami H, Koshiishi Y, Sasaki Y. The influence of relative body weight on toxicity of combination chemotherapy with cisplatin and etoposide. Cancer Chemother Pharmacol 1998;42:386-90. |
|4.||Meyerhardt JA, Tepper JE, Niedzwiecki D, Hollis DR, McCollum AD, Brady D, et al. Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: Findings from Intergroup Trial 0114. J Clin Oncol 2004;22:648-57. |
|5.||Esfahani A, Ghoreishi Z, Abedi Miran M, Sanaat Z, Ostadrahimi A, Eivazi Ziaei J, et al. Nutritional assessment of patients with acute leukemia during induction chemotherapy: Association with hospital outcomes. Leuk Lymphoma 2013; Nov 14 [Epub ahead of print]. |
|6.||Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55. |
|7.||Ma B, Yeo W, Hui P, Ho WM, Johnson PJ. Acute toxicity of adjuvant doxorubicin and cyclophosphamide for early breast cancer - a retrospective review of Chinese patients and comparison with an historic Western series. Radiother Oncol 2002;62:185-9. |
|8.||Hasenberg T, Essenbreis M, Herold A, Post S, Shang E. Early supplementation of parenteral nutrition is capable of improving quality of life, chemotherapy-related toxicity and body composition in patients with advanced colorectal carcinoma undergoing palliative treatment: Results from a prospective, randomized clinical trial. Colorectal Dis 2010;12:e190-9. |
|9.||Kaestner SA, Sewell GJ. Chemotherapy dosing part I: Scientific basis for current practice and use of body surface area. Clin Oncol (R Coll Radiol) 2007;19:23-37. |
[Table 1], [Table 2]