• Users Online: 249
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 425-426

Chemotherapeutic dose intensity and frailty: A subtle equilibrium

Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission14-May-2021
Date of Decision18-May-2021
Date of Acceptance20-May-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Suvir Singh
Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_104_21

Get Permissions

How to cite this article:
Singh S, Sharma R. Chemotherapeutic dose intensity and frailty: A subtle equilibrium. Cancer Res Stat Treat 2021;4:425-6

How to cite this URL:
Singh S, Sharma R. Chemotherapeutic dose intensity and frailty: A subtle equilibrium. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Aug 5];4:425-6. Available from: https://www.crstonline.com/text.asp?2021/4/2/425/320313

Bataillard et al. recently described the results of their systematic review that assessed the impact of the dose intensity of the cyclophosphamide, doxorubicin, vincristine, and prednisolone + rituximab (R-CHOP) regimen on survival in older patients with diffuse large B-cell lymphoma (DLBCL).[1] After screening 510 records, a total of 13 records were included in the final analysis. In studies reporting survival outcomes, it was observed that a reduced dose intensity of the R-CHOP regimen was associated with lower overall survival, irrespective of the patients' age (P < 0.05). When stratified by age, this effect was most pronounced for patients aged <80 years, while those aged more than 80 years demonstrated no consistent effects of the dose reduction. The key message from this analysis was to consider full-dose therapy for patients aged <80 years, considering its positive impact on the survival.

This study highlights several important aspects that need consideration before starting chemotherapy in older patients to balance the toxicity with clinical benefit. As a rule of thumb, all attempts must be made to administer optimal doses of chemotherapy for a maximal clinical response. A high incidence of treatment-related toxicity offsets the benefit obtained with chemotherapy and can lower the overall survival rates. Balancing efficacy and toxicity requires a fine balance between science (objectivity) and art (subjectivity); here, we provide a snapshot of the current data, reiterating the important message provided by this study.

DLBCL is primarily a disease of older adults, and the median age of onset has been reported to be between the sixth and seventh decades of life in the western countries. In contrast, in India, the median age at presentation has been reported to be 10–20 years lower than that reported by the western countries.[2],[3] Despite the lower median age at presentation, Indian patients appear to be more frail than their age-matched counterparts from the western countries, which ultimately impacts their response rates and survival. For instance, in a single-center analysis, Indian patients with DLBCL aged more than 60 years have been shown to have an overall survival as low as 9.5 months (range, 2–123 months).[4] An age cutoff as low as 40 years has been noted to predict for a lower overall survival in Indian patients with DLBCL.[5] Often, older patients or those with comorbidities do not receive full doses of anthracyclines or cytotoxic drugs, which explains the inferior outcomes in this cohort.[6]

Improvement in survival for DLBCL over the past three decades has disproportionately benefited patients from the younger age groups. Progress in the treatment outcomes of patients aged more than 85 years is still unsatisfactory, even in the high-income countries.[7] Therefore, until newer drugs or less toxic regimens become available, efforts must be made to administer the current agents at doses as close to the optimal calculated dose as possible to achieve maximal benefit. This can be meaningfully supported by an objective assessment of frailty. Accurate assessment of frailty at the time of diagnosis can enable more informed decision-making regarding dose adjustment or reduction without affecting the overall survival.[8] Recently, the simplified geriatric assessment score has been found to be capable of accurately categorizing patients with DLBCL into three groups with a clear demarcation of survival.[9] In India, population surveys have documented an objective evidence of frailty in 30%–40% of the people aged more than 60 years, and this is expected to be much higher in patients with DLBCL.[10] Considering the variations in frailty caused by ethnicity, it is imperative to validate similar tools in the Indian setting to obtain the corresponding cutoff values.

The present review provides a snapshot of important concepts in managing a common malignancy in older patients. Accurate assessment of frailty at diagnosis with indigenously validated tools will enable the administration of optimal doses of chemotherapy, which in turn will improve the overall response and survival rates.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bataillard EJ, Cheah CY, Maurer MJ, Khurana A, Eyre TA, El-Galaly TC. Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: A systematic review. Blood Adv 2021;5:2426-37.  Back to cited text no. 1
Babu SM, Garg S, Kanakasetty GB, Kuntegowdanahalli LC, Dasappa L, Rao SA. Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India. Indian J Cancer 2018;55:66-9.  Back to cited text no. 2
[PUBMED]  [Full text]  
Nair R, Arora N, Mallath MK. Epidemiology of non-Hodgkin's lymphoma in India. Oncology 2016;91 Suppl 1:18-25.  Back to cited text no. 3
Lokesh KN, Babu MC, Lakshmaiah KC, Babu KG, Saldanha SC, Loknatha D, et al. Diffuse large B-cell lymphoma in elderly: Experience from a tertiary care oncology center in South India. South Asian J Cancer 2017;6:72-4.  Back to cited text no. 4
[PUBMED]  [Full text]  
Ganesan P, Sagar TG, Kannan K, Radhakrishnan V, Rajaraman S, John A, et al. Long-term outcome of diffuse large B-cell lymphoma: Impact of biosimilar rituximab and radiation. Indian J Cancer 2017;54:430-5.  Back to cited text no. 5
[PUBMED]  [Full text]  
Huang HH, Ko BS, Chen HM, Chen LJ, Wang CY, Hsiao FY. Frontline treatments in extremely elderly patients with diffuse large B-cell lymphoma: A population-based study in Taiwan, 2010-2015. Immun Ageing 2020;17:17.  Back to cited text no. 6
Dinmohamed AG, Issa DE, van der Poel MW, Schouten HC, Lugtenburg PJ, Chamuleau ME, et al. Treatment and relative survival in very elderly patients with DLBCL in The Netherlands: A population-based study, 1989 to 2015. Blood Adv 2017;1:1839-41.  Back to cited text no. 7
Noronha V, Ramaswamy A, Dhekle R, Talreja V, Gota V, Gawit K, et al. Initial experience of a geriatric oncology clinic in a tertiary cancer center in India. Cancer Res Stat Treat 2020;3:208-17.  Back to cited text no. 8
  [Full text]  
Merli F, Luminari S, Tucci A, Arcari A, Rigacci L, Hawkes E, et al. Simplified geriatric assessment in older patients with diffuse large B-cell lymphoma: The prospective elderly project of the fondazione italiana linfomi. J Clin Oncol 2021;39:1214-22.  Back to cited text no. 9
Dasgupta A, Bandyopadhyay S, Bandyopadhyay L, Roy S, Paul B, Mandal S. How frail are our elderly? An assessment with Tilburg frailty indicator (TFI) in a rural elderly population of West Bengal. J Family Med Prim Care 2019;8:2242-8.  Back to cited text no. 10
[PUBMED]  [Full text]  


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article

 Article Access Statistics
    PDF Downloaded9    
    Comments [Add]    

Recommend this journal