PONE-D-21-17359

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

PLOS ONE

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PLOS ONE

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: The authors have explored the impact of the initial dose of enzalutamide on the treatment response and incidence of AEs in patients with CRPC. They report that initial dose modification of enzalutamide did not decrease the incidence of AEs and might impair the efficacy. The topic is clinically significant as the patients are getting older, as written in the manuscript. The manuscript is concise and well-written. Some points to be clarified are as below.

1) In the univariate and multivariate analysis, 'Time to CRPC <12m' is independent risk factor for the prediction of PSA progression-free survival (Table 4). Then, I suppose some patients who had long, durable response with previous ADT (Time to CRPC >12m) might be treated with initial dose reduction. In contrast, some with resistant to ADT might be treated without dose modification. So , Could you check and provide subgroup analysis between these two group according to Time to CRPC?

2) It would be good to provide relative dose intensity if you can calculate from the subjects.

3) In Table 2, the Median time to CRPC (IQR) of the two groups seems different (median time 10.5 vs. 20.5). Although, P-value is not statistically significant. I recommend checking this value and provide other values, such as mean time or distribution if possible.

4) Please add abbreviations to each table.

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Reviewer #1: No

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Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

PONE-D-21-17359R1

Dear Dr. Tsuzuki,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Henry Woo

Academic Editor

PLOS ONE