Patients with metastatic castration-resistant prostate cancer (mCRPC) have a lower risk of developing grade 3 or 4 neutropenia, likely due to less exposure to docetaxel.
Compared with other solid tumor types, patients with metastatic castration-resistant prostate cancer (mCRPC) have a lower risk of febrile neutropenia, a new meta-analysis has revealed.
The lower risk is likely attributable to less exposure to docetaxel, according to the study researchers. Currently, docetaxel is approved for the treatment of multiple solid tumors, including breast cancer, head and neck cancer, gastric adenocarcinoma, non—small cell lung cancer, and mCRPC.
The meta-analysis included 36 cohorts from 26 trials who were treated with docetaxel, either as monotherapy or in combination with chemotherapy or targeted therapy, between January 2006 and January 2016 at the Netherlands Cancer Institute or the Medical Center Slotervaart in Amsterdam, the Netherlands. The researchers extracted data on patient characteristics, neutrophil counts at cycle 1, and cancer types.
A total of 812 patients were included in the analysis, 115 of whom had mCRPC and 697 had other solid tumors. The most common types of other solid tumors included breast, lung, gastric/esophagus, and head and neck cancers. Across the studies, patients with mCRPC had a 1.8-fold lower exposure to docetaxel compared with other solid tumors (1.82 mg h/L vs 3.30 mg h/L, respectively).
“The mechanism behind the decreased exposure to docetaxel in the mCRPC patients remains to be elucidated,” wrote the researchers. “Possibly, castration levels of testosterone cause an increase in elimination and thus lower exposure of docetaxel.”
The researchers also pointed out that patients with prostate cancer receiving docetaxel concurrent with androgen deprivation therapy in an early stage of the disease have castration levels of testosterone, but these patients experience more toxicity compared with castration-resistant patients receiving docetaxel in a later stage of disease. Therefore, they wrote, it’s likely that length of treatment with androgen deprivation therapy is important in pharmacokinetic changes of docetaxel in patients with mCRPC.
The analysis also revealed that patients with mCRPC were also significantly less likely to develop grade 3 or 4 neutropenia compared with other patients, with an odds ratio of 0.46. Neutropenia occurred in 7.8% of patients with mCRPC and in 16.5% of patients with other solid tumors. According to the researchers, patients who received a dose of 100 mg/m3 or more of docetaxel were more likely to develop grade 3 or 4 neutropenia.
The researchers noted that concomitant administration of other types of chemotherapy was not associated with an increased risk of neutropenia.
Schultink A, Crombag M, Werkhoven, et al. Neutropenia and docetaxel exposure in metastatic castration-resistant prostate cancer patients: a meta-analysis and evaluation of a clinical cohort [published online February 22, 2019]. Cancer Med. doi: 10.1002/cam4.2003.