Risk factors for chemotherapy toxicity in elderly are identified

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CHICAGO—A risk stratification schema can be used to identify older patients who are at risk of grade-3 to -5 toxicity from chemotherapy. The schema includes risk factors based on cancer type, patient age, upfront dose of chemotherapy, the chemotherapeutic regimen used, and history of falling, among others, said Arti Hurria, MD at the 46th American Society of Clinical Oncology annual meeting.
“We wanted to develop a predictive model for tolerance to therapy in older adults with cancer,” she said.
To this end, 500 cancer patients 65 years or older from seven institutions completed a prechemotherapy assessment that captured sociodemographic characteristics, tumor characteristics, treatment characteristics, laboratory values, and geriatric assessment parameters. Chemotherapy toxicity was subsequently graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Two physicians graded toxicity to adjudicate whether or not the toxicity was due to the chemotherapy. Patients were followed until the end of the chemotherapy regimen.
The geriatric assessment included functional status (including Karnofsky Performance Rating Scale), comorbidity, cognition, psychological status, social functioning, social support, and nutrition (body mass index and the percentage of body weight lost in the past 6 months).
The most common tumor type was lung, in 144 patients, followed by gastrointestinal (137), gynecologic (86), breast (56), urologic (50), and other (27). Sixty percent of the patients had stage IV disease, 70% received polychemotherapy, and 18% received white blood cell growth factor with cycle 1 of treatment.
Almost half (43%) required assistance with instrumental activities of daily living (IADLs), 18% had fallen within the past 6 months, 44% had more than 2 comorbidities, and 38% had weight loss of at least 5% in past 6 months.
“Fifty three percent had grade-3 to -5 toxicity that was adjudicated as being secondary to chemotherapy,” said Hurria, the vast majority being grade-3 toxicity. Grade 3- to -5 hematologic and nonhematologic toxicity occurred in 26% and 43% respectively.
The most common grade-3 to -5 hematologic toxicities were low absolute neutrophil count (11%), low white blood cell count (10%), and low hemoglobin levels (10%); the most common nonhematologic toxicities were fatigue (16%), infection (9%), and dehydration (9%).
On the first model developed (through multivariate analysis), predictors of chemotherapy toxicity were age 73 years or older, gastrointestinal or genitourinary cancers, standard-dose chemotherapy given upfront, receipt of polychemotherapy, falls within the past 6 months, assistance required in IADLs, and decreased social activity.
Individuals with zero to two risk factors had a 34% chance of toxicity, those with three to four risk factors had a 54% chance of toxicity, and those with five to seven risk factors had an 85% risk of toxicity, said Hurria, director of the Cancer and Aging Research Program at City of Hope in Duarte, California.
The first model was then refined through an internal validation process, calibration of the data, and further analysis of individual items in the geriatric assessment measure (to increase ease of administration and scoring), and yielded the following risk factors for grade-3 to -5 toxicity:
  • Age 73 years or older
  • Gastrointestinal or genitourinary cancers
  • Standard-dose chemotherapy
  • Receipt of polychemotherapy
  • Low hemoglogin levels (<11 g/dL male; <10 g/dL female)
  • Low creatinine clearance (Jelliffe-ideal weight <34)
  • Falls in the past 6 months
  • Hearing impairment (fair or worse)
  • Limited in walking one block
  • Assistance required in medication intake
  • Decreased social activity

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