Dose Intensity and Hematologic Toxicity in Older Cancer Patients Receiving Systemic Chemotherapy.
Authors: Shayne Michelle , Culakova Eva , Poniewierski Marek S. , Wolff Debra , Dale David C. , Crawford Jeffrey , Lyman Gary H. 
Published: April 2020

Abstract
Introduction: Controlled clinical trials have provided limited data on hematologic toxicity and dose intensity of chemotherapy in the elderly. This study evaluated patient and treatment characteristics that contributed to hematologic toxicity in older cancer patients.
Methods: A prospective study of 115 randomly selected U.S. community oncology practices was undertaken between March 2002 and March 2005 that included 999 consecutive patients age 70 and older. Major malignancies included cancers of lung (26%), colorectal (15%), lymphoma (13%), breast (13%), ovary (9%), genitourinary (7%), other gastrointestinal (6%), other gynecologic (3%) and head and neck (2%). Primary outcome measures included: anemia (Hgb &lt;10 gm/dL), thrombocytopenia (plts &lt;75k/mm3), severe neutropenia (SN) (neutrophils &lt;500 cells/mm3, or WBC count &lt;1000/mm3), febrile neutropenia (FN) and both planned and actual relative dose intensity (RDI) compared to standard regimens. Univariate and multivariate logistic regression analyses were performed to compare the difference among patients age 70–74 (45%), 75–79 (34%), ≥ 80 (21%).
Results: Increasing age was associated with lower actual RDI (P&lt;001), although planned RDI did not differ among age groups. Along with reduced actual RDI in elderly patients, progressively fewer SN or FN events (25%, 24%, and 16%, respectively) occurred across chemotherapy cycles (P=0.036). More advanced stage of disease at the time of treatment was associated with fewer SN or FN events in all cycles (35%, 27%, 21%, and 19% for stages 1–4, respectively) (P=0.017) along with lower RDI (P=.041). Use of taxane-containing regimens decreased with advancing age (37%, 34%, 27%, respectively) (P=0.034). Among the 50% of patients receiving ≥ 85% RDI, there was no significant difference in SN or FN based on age group or stage. Use of anthracycline-containing regimens was associated with development of SN or FN compared to non-anthracycline regimens (P&lt;0.001). Older patients who received ≥ 85% actual RDI experienced more frequent SN or FN in all cycles of chemotherapy (27%) compared with patients who received &lt;85% (22%) (P=.041) although no significant increase with age was observed. There was no statistically significant difference in anemia or thrombocytopenia among the different age groups. Anemia and thrombocytopenia were more prevalent in older patients receiving an anthracycline or platinum-containing regimen. In multivariate analysis, lower risk of SN or FN remained significantly associated with increasing age (P=.044) after adjustment for stage (P=.115) and actual RDI (P=.066). Prophylactic colony-stimulating factor was used in 5% of patients with no significant difference observed among the age groups.
Conclusion: This report represents one of the largest studies to date of elderly cancer patients receiving chemotherapy. Neutropenic events increased with actual RDI while decreasing with age and disease stage. Advancing age alone does not appear to increase the risk of hematologic toxicity in older patients receiving full dose intensity chemotherapy. Nevertheless, half of elderly patients in this study received major reductions in actual dose intensity. More information is needed on the impact of reduced dose intensity chemotherapy on long term clinical outcomes in this population.