Chemotherapy dose adjustment after severe toxicity in older cancer patients

Abstract

9627 Background: About 60% of older cancer patients experience a grade 4 hematologic (G4H) toxicity and/or a grade 3–4 non- hematologic (G3–4NH) toxicity from chemotherapy. Yet, the mean dose intensity of their treatment is 90% (Extermann et al., 2002). This suggests that oncologists might use alternative strategies to dose reduction. No data exist as to the safety of these alternative strategies. Methods: We reviewed the data from 2 prospective studies of tolerance to chemotherapy in older patients. The dose modifications were left at the discretion of the physicians. Toxicity data were prospectively collected for up to 6 months and rated with CTC 3.0. We assessed whether the treatment was modified in response to G4H, G3–4NH, or either (severe toxicity). We assessed what the modification was, whether patients experienced subsequent severe toxicity, and the reason for stopping treatment. Results: In our sample of 205 patients (age 70- 92, median 75), 72% had a severe toxicity: 35% G4H, 59% G3–4NH, and 24% both. Treatment was modified in 59% of patients with G4H, 56% with G3–4NH, and 57% with both. A modification was made for 85 patients: 22 interruptions of treatment, 25 dose reductions, 13 delays without dose reduction, 21 modified regimens, 3 additional anti-emetics, 2 prophylactic anti-infectious agents, 1 addition of G-CSF, and 1 potassium replacement. Subsequently, 37% of patients who had a modification experienced further severe toxicity, versus 14% of the patients who did not have a modification (p<0.002). Baseline age, sex, BMI, tumor stage, comorbidity, depression, and functional, nutritional, or cognitive status had little or no correlation with the decision to modify the treatment. Conclusions: Most older cancer patients experience a severe toxicity from their chemotherapy. Yet, 2 out of 5 do not undergo chemotherapy modification after it. Oncologists appeared able to effectively identify patients in whom it was safe to continue a full-dose regimen, although this study could not identify clear explanatory mediators. Therefore, requiring a systematic dose reduction for severe toxicity in therapeutic trials and practice might lead to undertreatment of older cancer patients. Research to establish more nuanced treatment modification guidelines needs to be conducted. No significant financial relationships to disclose.