Assessment of Hematologic and Non-Hematologic Toxicity in Older Cancer Patients Receiving Systemic Chemotherapy: Results from a Prospective Nationwide Registry.

Introduction: Although 60% of all malignancies occur in patients ≥65, this population is poorly represented in cancer clinical trials. While fit elderly patients appear to tolerate chemotherapy as well as younger individuals, less is known about chemotherapy tolerance in older cancer patients with poor performance status or co-morbidities. The purpose of this study was to examine the impact of patient and disease characteristics on the reported toxicities of cancer chemotherapy.

Methods: This study represents part of a prospective, nationwide registry based at 137 randomly selected practice sites throughout the US. The major malignancies considered were cancers of the breast (33%), colon (10%), lung (19%) and ovary (7%) along with malignant lymphoma (8%). To date, 3422 patients have been registered of which 2719 are available for analysis including 1083 patients age ≥65 (40%). Primary outcome measures were: relative dose intensity (RDI) compared to standard doses, anemia (Hgb <10), neutropenia (neutrophils <1000) and non-hematologic toxicities pertinent to older adults including stomatitis, diarrhea, anorexia, dehydration and weight loss. Univariate and multivariate logistic regression analysis was performed to compare the difference between the 65–74 and ≥75 age groups.

Results: Complete data were available on 927 patients ≥65 years of age. Among breast cancer patients, increasing age (<65, 65–74, ≥75) was associated with progressively less Grade III/IV neutropenia (62%, 51% and 41%), respectively (p=0.006). This corresponds to patients receiving progressively less RDI (93.4%, 91.3%, 89.8%; P=.025) with 17%, 19% and 25% receiving RDI <85%, respectively. Most of the reduced RDI was planned in patients ≥75 years compared with less than half in younger patients (P=.035). Non-breast cancer patients experienced no significant difference in rates of Grade III/IV neutropenia by age. Increasing age was associated with progressively more anemia (27%, 34%, and 44%) respectively (p<0.0001) among non-breast cancer patients but not among those with breast cancer. Despite a trend, no significant increase in non-hematologic toxicities was observed with increasing age in breast cancer or non-breast cancer patients. Factors significantly associated with Grade III/IV neutropenia in univariate analysis included baseline ANC <3000, BSA<2.0, female gender and anthracycline containing regimens. In multivariate analysis, after adjusting for tumor type and performance status the following were significant predictors of Grade III/IV neutropenia: BSA<2.0 (OR=1.5 p=0.04), Baseline ANC<3000 (OR=2.0 p=0.001) and anthracycline containing regimen (OR=3.5 p<0.0001). Factors associated with non-hematologic toxicity in univariate analysis included colon cancer (p<0.0001), Charlson Co-morbidity Index (CCI) ≥ 3 (p=0.068), ECOG performance status ≥2 (p=0.05), and 5-Fluorouracil containing regimens (p<0.0001) while in multivariate analysis, only the CCI maintained a trend towards increased non-hematologic toxicity (p=0.069).

Conclusions: While anemia increases with age in non-breast cancer patients, neutropenia decreases with increasing age in breast cancer patients, most likely as a result of age-related reductions in RDI.