AI Article Synopsis

  • Enzalutamide is a key drug for metastatic prostate cancer, but standard doses often lead to side effects requiring reductions; this study examined the effects of starting with a lower dose (≤50%) on patient outcomes.
  • Researchers analyzed records from 111 patients and compared low-dose (≤80 mg/day) to standard-dose (160 mg/day) enzalutamide regarding survival outcomes (overall and progression-free survival).
  • Results showed no significant difference in overall or progression-free survival between the doses, but low-dose patients had a better longevity, reflected in a longer average attained age (89.1 years) compared to those on the standard dose (83.8 years).

Article Abstract

Background: Enzalutamide is an important drug in the treatment of prostate cancer. Standard dosing often requires dose reduction because of side effects. There is no information on survival outcomes with lower doses. We investigated the impact of starting enzalutamide at ≤ 50% dose on metastatic prostate cancer outcomes including patients' longevity.

Patients And Methods: Records of metastatic prostate cancer patients treated with enzalutamide at one center were retrospectively reviewed. Low-dose enzalutamide (≤80 mg/day) was compared with standard-dose (160 mg/day). The primary objective was to compute the restricted mean survival time (RMST - time scale) and restricted mean attained age (RMAA - age scale) using the Irwin method. Secondary objectives included overall survival (OS), progression-free survival (PFS), and PSA progression per PCWG3 criteria (PSA PFS). We used the logrank test and the ∆ difference between RMSTs for comparison.

Results: Of 111 patients treated, 32 received a low-dose and 79 the standard-dose. Low-dose patients had less prior abiraterone or chemotherapy (28.1% vs. 65.8%, P < .001); more testosterone assessment (65.6% vs. 40.5%, P = .016); poorer ECOG performance status (48.3% score ≥2 vs. 26.6%; P = .040), more comorbidities (75.9% vs. 46.3%; P = .010)) including increased cardiovascular disease (51.7% vs. 21.4%, P = .004). Baseline PSA value and doubling time at start of enzalutamide and distribution of metastases were similar between the groups. OS and PFS did not differ between low-dose and standard-dose. Patients on low-dose had a better longevity with significantly longer RMAA, 89.1 years, versus standard-dose RMAA of 83.8 years (∆ = 5.3 years, P = .003, logrank P = .025). In a subgroup analysis by age at start of enzalutamide, <75 versus ≥75 years old, longevity was also better with low-dose in younger patients (∆ = 2.9 years, P = .034, and older, ∆ = 3.3 years, P = .011).

Conclusion: The longevity advantage and reduced adverse events seen in patients with prostate cancer treated with low-dose enzalutamide warrants further investigation.

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Source
http://dx.doi.org/10.1016/j.clgc.2022.05.012DOI Listing

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