Impact of geriatric covariates on metronomic cyclophosphamide efficacy and tolerance—the CHEMETROLD study

BACKGROUND: Metronomic cyclophosphamide is sometimes considered in older or frail patients with advanced cancer when disease-related symptoms affect quality of life and standard treatments are no longer suitable. While clinical feedback on its tolerance and efficacy is often positive, the evidence remains limited in geriatric, comorbid populations. PATIENTS AND METHODS: This retrospective, monocentric study evaluated the impact of patient-, tumour-, and treatment-related characteristics on the efficacy and safety of metronomic cyclophosphamide in patients aged ≥70 years with metastatic solid tumors. Baseline geriatric assessments were collected, and treatment exposure, tolerance, and outcomes were analyzed. An exploratory subgroup analysis focused on patients treated for ≥9 months. RESULTS: Thirty-seven patients (median age 84 years, range 70-96) were included: 15 had prostate cancer (40.5%), 8 breast cancer (21.6%), and 14 other primary tumors (37.8%). The median treatment duration was 4 months; the median progression-free survival was 4 months and 6 months in breast and prostate cancer subgroups. Overall dose intensity was 87%, with 62.2% of patients maintaining ≥90%. Treatment was generally well tolerated; only 5 grade ≥3 toxicities were reported, and 83.7% of patients remained at home during therapy. Notably, patients treated for ≥9 months had a poorer performance status and lower functional scores at baseline. No specific molecular alterations were associated with prolonged treatment benefit. CONCLUSION: Metronomic cyclophosphamide appears to be a safe and potentially effective option in older and frail patients with metastatic cancer, including those with limited functional reserve. These findings support its use as a pragmatic alternative to supportive care, even in late disease stages.