First‐ and second‐line chemotherapy with docetaxel or mitoxantrone in patients with hormone‐refractory prostate cancer

Abstract

BACKGROUNDDocetaxel and mitoxantrone are considered first‐line chemotherapeutic options in patients with hormone‐refractory prostate cancer (HRPC), but their clinical effectiveness in a second‐line setting is unknown. Therefore, the authors conducted a population‐based retrospective study to establish activity and tolerability of second‐line docetaxel or mitoxantrone in HRPC.METHODSThe study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression‐free survival (PFS), posttreatment prostate‐specific antigen (PSA) decline of ≥ 50% and treatment‐related toxicity were evaluated.RESULTSOf 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first‐line had a trend toward longer median OS compared with patients treated with second‐line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2–26.8 mos vs. 15 mos, 95% CI, 10.4–19.6 mos). Median number of second‐line chemotherapy cycles was 3 and median PFS survival was 2–3 months in both groups. Second‐line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second‐line docetaxel and mitoxantrone were associated with a high frequency of treatment‐related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively).CONCLUSIONSStudy results favored docetaxel given up‐front for patients with HRPC considered suitable for further chemotherapy. Second‐line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second‐line chemotherapy, should be enrolled into clinical trials. Cancer 2006. © 2006 American Cancer Society.

The 2014 CUA-CUOG Guidelines for the Management of Castration Resistant Prostate Cancer (CRPC)

“…12 The timing of docetaxel therapy in men with evidence of metastases, but without symptoms, should be discussed with patients and therapy should be individualized based on patients' clinical status and preferences (Level 3, Grade C).…”

Chemotherapy for hormone-resistant prostate cancer: Where are we today?

“…Moreover, 46% of patients in the mitoxantrone-after-docetaxel group and 64% patients in the docetaxel-after-mitoxantrone group had to have dose reduction, delay or cessation of chemotherapy or hospitalization as a result of toxicity. [34] Other studies confirmed the activity of taxane-based chemotherapy before or after mitoxantrone but the duration of responses is short and there is no difference in OS or PFS regardless of the drug sequence used. [35]…”

“…[33] The largest of crossover trials comparing docetaxel and mitoxantrone as second-line agents was published by Michels et al . [34] These authors found that second-line docetaxel after first-line mitoxantrone-based chemotherapy produced better PSA responses than second-line mitoxantrone after docetaxel. Despite the PSA responses, neither of these strategies improved PFS or OS, which were two to three months and seven to 12 months, respectively.…”

A review of treatments targeting DNA-repair gene defects in metastatic castration resistant prostate cancer

“…These treatments include second generation androgen receptor blockers, inhibition of androgen biosynthesis with an agent such as abiraterone (6), and taxane chemotherapy with docetaxel or cabazitaxel (7). There have been studies using mitoxantrone but multiple studies have shown increased toxicity with response rates between 9-20% (7)(8)(9)(10). Radium 223 is also approved for use in castrate resistant prostate cancer with bone metastases (11).…”