|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 2 | Page : 425-426
Chemotherapeutic dose intensity and frailty: A subtle equilibrium
Suvir Singh, Rintu Sharma
Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
|Date of Submission||14-May-2021|
|Date of Decision||18-May-2021|
|Date of Acceptance||20-May-2021|
|Date of Web Publication||30-Jun-2021|
Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab
Source of Support: None, Conflict of Interest: None
|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
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). 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., 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). An age cutoff as low as 40 years has been noted to predict for a lower overall survival in Indian patients with DLBCL. 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.
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. 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. 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. 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. 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.
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Conflicts of interest
There are no conflicts of interest.
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