Br J Clin Pharmacol. 2020 Oct 19. doi: 10.1111/bcp.14614. Online ahead of print.
AIM: Chemotherapy-induced neutropenia has been associated with an increase in overall survival in non-small cell lung cancer patients. Therefore, neutrophil counts could be an interesting biomarker for drug efficacy as well as linked directly to toxicity. For drugs where neutropenia is dose limiting, neutrophil counts might be used for monitoring drug effect and for dosing optimisation.
METHODS: The relationship between drug effect on the 1st cycle neutrophil counts and patient survival was explored in a Phase III clinical where patients with non-small cell lung cancer were treated with docetaxel. Once the association has been established, dosing optimisation was performed for patients with severe toxicities (neutropenia) without compromising drug efficacy (overall survival).
RESULTS: After taking into account baseline prognostic factors, such as ECOG performance status, smoking status, liver metastasis, tumour burden, neutrophil counts and albumin levels, a model-predicted drug effect on the 1st cycle neutrophil counts was strongly associated with patient survival (p=0.005). Utilizing this relationship in a dose optimisation algorithm, 194 out of 366 patients would have benefited from a dose reduction after the 1st cycle of docetaxel. The simulated 1-year survival probabilities associated with the original dose and the individualised dose were not different.
CONCLUSION: The strong relationship between drug effect on the 1st cycle neutrophil counts and patient survival suggests that this variable could be used to individualise dosing, possibly without needing PK samples. The algorithm highlights that doses could be reduced in case of severe haematological toxicities without compromising drug efficacy.