Frequency and Determining Factors of Empiric Chemotherapy Dose Reduction

To determine the frequency and key factors regarding empiric chemotherapy dose reductions (ECDR) in nonsmall cell lung cancer (NSCLC) patients.

Empiric chemotherapy dose reduction

Non-small cell lung cancer (NSCLC) is a disease of the elderly with a median age diagnosis at seventy-one years of age . Unfortunately, the risk of chemotherapy toxicities, such as mucositis, myelosuppression, neuropathy, and cardiomyopathy, increases with advancing age .

It has been estimated that frailty in elderly cancer patients can be as high as 42% . This has led to the practice of empiric chemotherapy dose reductions (ECDR) in elderly patients to prevent morbidity and mortality . A multisite cohort study involving elderly cancer patients demonstrates that 29% of those with advanced cancer have experienced a dose reduction in their first chemotherapy cycle .

There are existing guidelines on chemotherapy dosage for patients with NSCLC . However, no guidelines are available in assisting physicians on how to manage patients with NSCLC who may also require ECDR. For that reason, clinical judgment and experience play a significant role in treatment decisions.

However, this may result in potential biases and variation among physicians. Therefore, it is imperative to seek and understand the possible variables to avoid unnecessary chemotherapy toxicities in the frail elderly or under treatment of fit elderly patients. To date, there are few existing studies that explore potential factors in ECDR in specific population such as elderly and obesity but not in NSCLC population . This study aims to determine the frequency and key factors regarding empiric chemotherapy dose adjustments in patients with NSCLC.

Our studies indicated that medical oncologists in Sunnybrook Health Sciences Complex considered moderate stage of chronic kidney disease to determine whether or not they performed ECDR. In addition, our study suggested that medical oncologists considered multiple combined impacting factors – 3 or more of aged 61 or above, polypharmacy, presence of kidney disease (particularly in moderate stage), and palliative intent – rather than a single factor to determine the practice of ECDR. The extent to which ECDR was performed (i.e. dose reduction of 10% or less, 11%-20%, or 21% or above) were correlated with patient age, moderate stage chronic kidney disease, and having combinations of impacting factors.

The treatment goals in our patient population of advanced NSCLC should focus on symptom relief, quality of life improvement, and possible survival prolongation . Current BCCA guidelines recommend to not extend platinum-based doublet chemotherapy beyond 4 to 6 cycles as first-line palliative chemotherapy, given that it might not provide survival benefit but increase cumulative toxicity profiles. Instead, the guideline recommends a single agent maintenance therapy when appropriate. This was consistent with our finding of palliative intent as one of the major factors in performing ECDR.

Despite the limitations, our study provided some understanding in the factors determining the presence of ECDR. Future studies evaluating patient outcomes in multiple cancer centers secondary to empiric dose reductions are recommended. Such findings will be useful in developing guidelines in the future.

conclusion

More studies are required in the future to examine the variances in ECDR amongst medical oncologists, which might lead to clinically significant outcomes. As our population ages rapidly, the incidence of ECDR would increase dramatically. Thus, it is important to increase awareness of such dosing patterns and to further evaluate the association between ECDR and its intended outcomes in future studies.

This article published by SciDocPublishers in " International Journal of Cancer Studies & Research". Read the original article.