Weekly Docetaxel in Elderly Patients with Prostate Cancer: Efficacy and Toxicity in Patients Aged ≥ 70 Years Compared with Patients Aged < 70 Years

doi:10.3816/CGC.2003.n.025

Clinical Prostate Cancer

Volume 2, Issue 3, December 2003, Pages 167-172

https://doi.org/10.3816/CGC.2003.n.025 Get rights and content

Abstract

We sought to determine whether age was significantly associated with efficacy and toxicity of weekly docetaxel in patients with metastatic androgen-independent prostate cancer (AIPC). Individual patient ata were pooled from 2 phase II clinical trials of weekly docetaxel 36 mg/m² for 6 of every 8 weeks in men with metastatic AIPC. Baseline characteristics and outcome measures of men ≥ 70 years of age (n = 52) were compared with patients < 70 of age (n = 34) using Pearson χ² test for categorical variables, Mann-Whitney U test for continuous variables, and log-rank test of Kaplan-Meier estimates for time-dependent variable. Multivariate analysis was used to adjust for any imbalances in baseline characteristics. At baseline, older patients had a lower hemoglobin level (P = 0.05) and a higher serum prostate-specific antigen (PSA; P = 0.04). The PSA response rate was 47% (95% CI, 33%–62%) in older patients and 40% (95% CI, 23%–59%) in younger patients (P = 0.75). Similarly, measurable disease response rate (P = 0.43), time to progression (P = 0.28), and survival (P = 0.52) were not affected by age in both univariate and multivariate analyses. There was also no difference in overall hematologic and nonhematologic toxicity ≥ grade 2. This comparison of pooled individual patient data from 2 phase II studies of weekly docetaxel in AIPC did not reveal significant differences in efficacy or toxicity in men aged ≥ 70 years compared with younger patients. These findings are consistent with the hypothesis that docetaxel chemotherapy in patients with AIPC is equally well tolerated and effective across a wide range of ages.

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Cited by (49)

Plasma androgen receptor and response to adapted and standard docetaxel regimen in castration-resistant prostate cancer: A multicenter biomarker study
2021, European Journal of Cancer
Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown.
This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician. Upon analysis, patients were assigned randomly to either a training (n = 217) or validation (n = 108) cohort.
In the training cohort, AR-gained patients treated with adapted docetaxel regimen had a significantly worse median progression-free survival (PFS) (3.8 vs 6.3 months, hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.34–4.95, p < 0.0001), median overall survival (10.8 vs 20.6 months, HR 1.98, 95% CI 1.09–3.62, p = 0.0064) and PSA response (PSA > −50%: odds ratio 4.88 95%CI 1.55–14.32, p = 0.013) as compared to plasma AR normal patients. These findings were all confirmed in the validation cohort. However, in patients treated with standard docetaxel regimen, these differences were not seen. The interaction between AR CN status and dose reduction of docetaxel was considered as independent factor for PFS in both the training and validation cohort (HR 2.84, 95% CI 1.41–5.73, p = 0.003, and HR 4.79, 95% CI 1.79–12.82, p = 0.002).
Despite the retrospective non-randomised design of this study, our hypothesis-generating findings could suggest plasma AR as a potential biomarker for optimal docetaxel timing and dose in mCRPC patients. Prospective trials are warranted.
Characterizations of Clinical and Therapeutic Histories for Men with Prostate Cancer-Specific Mortality
2016, Clinical Genitourinary Cancer
Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC). Unique to the present study is the unequivocal attribution of PCa death by a single experienced clinician.
A total of 119 patients who had been treated at Tulane Cancer Center and had died of mCRPC from 2008 to 2015 were studied through a retrospective review of the medical records.
The median age at diagnosis was 65 years (range, 40-85 years), and 34.4% of the patients presented with metastatic disease (stage M1). Of these patients, 56% had received definitive primary therapy, all had received androgen-deprivation therapy, and 52% had received docetaxel. The patients had received a median of 7 (1-14) systemic therapies before death. Most were secondary hormonal manipulations after the diagnosis of mCRPC (median, 4; range, 0-9). The median survival was 69 months (range, 5-270 months) after diagnosis, and the median age at death was 73 years (range, 47-95 years). The presence of metastases at diagnosis was a significant predictor of early death (hazard ratio, 4.33; P < .001), and definitive primary therapy was a significant predictor of longer survival (P < .001). The median survival for patients presenting with metastases was 39 months (range, 5-235 months) compared with 100 months (range, 6-270 months) for those with localized disease (P < .001). The median age at diagnosis between the docetaxel- and non–docetaxel-treated patients was significantly different at 62 and 71 years, respectively (P = .002).
The present retrospective analysis provides initial views clarifying the clinical characteristics of men dying of mCRPC and the therapies they received before death. Additional data are needed in multi-institutional settings to confirm these findings.
Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy
2014, European Urology
Metastatic castration-resistant prostate cancer (mCRPC) is a disease that primarily affects older men. Abiraterone acetate (AA), a selective androgen biosynthesis inhibitor, in combination with low-dose prednisone (P) improved overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel versus placebo (PL) plus P.
To examine the efficacy and safety of AA plus P versus PL plus P in subgroups of elderly (aged ≥75 yr) (n = 331) and younger patients (<75 yr) (n = 863).
We conducted a post hoc analysis of a randomised double-blind PL-controlled study in mCRPC patients progressing after docetaxel chemotherapy.
Patients were randomised 2:1 to AA (1000 mg) plus low-dose P (5 mg twice daily) (n = 797) or PL plus P (n = 398).
Primary end point was OS. Secondary end points were time to prostate-specific antigen (PSA) progression (TTPP), radiographic progression-free survival (rPFS), and PSA response rate. Treatment differences were compared using the stratified log-rank test. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). The key limitation was the post hoc analysis.
Elderly patients treated with AA plus P showed improved OS (HR: 0.64; 95% CI, 0.478–0.853; p = 0.0022), TTPP (HR: 0.76; 95% CI, 0.503–1.155; p = 0.1995), and rPFS (HR: 0.66; 95% CI, 0.506–0.859; p = 0.0019), and higher PSA response rate with relative risk (HR: 4.15; 95% CI, 2.2–8.0]; p ≤ 0.0001) compared with patients treated with PL plus P. Grade 3/4 adverse events occurred in 62% of elderly patients and in 60% of patients aged <75 yr treated with AA plus P. Incidences of hypertension and hypokalaemia, although increased in the AA plus P arm, were similar in both age subgroups and readily managed.
AA improves OS and is well tolerated in both elderly patients and younger patients with mCRPC following docetaxel, hence providing an important treatment option for elderly patients who may not tolerate alternative therapies with greater toxicity.
ClinicalTrials.gov, identifier NCT00638690.
Tolerability and efficacy of docetaxel in older men with metastatic castrate-resistant prostate cancer (mCRPC) in the TAX 327 trial
2014, Journal of Geriatric Oncology
Prostate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population.
Two subgroup analyses of TAX 327 were conducted. Among patients receiving DPq3w, tolerability and efficacy were compared between three age groups: < 65, 65–74 and ≥ 75 years. For men ≥ 75 years, these outcomes were compared between DPq3w, DPq1w, and mitoxantrone (MP) arms. Tolerability outcomes included dose delivery, grade 3/4 adverse events and quality of life. Efficacy outcomes included overall survival and tumor response.
Of 1006 men with metastatic castrate-resistant prostate cancer (mCRPC) in the trial, 335 received DPq3w. Among these, 20% were age ≥ 75 years. For DPq3w, there were non-significant associations of worse tolerability and efficacy with advancing age. Twenty-eight percent of men age ≥ 75 years had an objective pain response, compared to 38% and 34% of patients 65–74 and < 65 years, respectively. There were no significant differences in prostate-specific antigen (PSA) response (43–48%, p = 0.74) or measurable tumor response (7–17%, p = 0.30) according to age. Among men ≥ 75 years, DPq3w resulted in more dose reductions than DPq1w (22% versus 8%, p = 0.007), but tolerability was otherwise comparable. Both were associated with more favorable efficacy than mitoxantrone.
Tolerability and efficacy of DPq3w appear less favorable with advancing age. Compared to DPq1w, DPq3w is associated with better survival outcomes, but similar tolerability, and remains the standard first-line chemotherapy option in mCRPC. Toxicity is substantial, therefore careful patient selection, close monitoring and early management of toxicities is advised.
The Experience with Cytotoxic Chemotherapy in Metastatic Castration-Resistant Prostate Cancer
2012, Urologic Clinics of North America
Citation Excerpt :
Docetaxel, given intravenously every 3 weeks (75 mg/m2) to men with prostate cancer in an initial small trial (n = 35), was associated with a 46% serum PSA response rate.17 In a series of clinical trials featuring intravenous weekly docetaxel (35–40 mg/m2), serum PSA response rates ranged from 41% to 64%.18–22 The addition of estramustine (see earlier discussion) to docetaxel appeared to produce significant benefits in early studies, both for serum PSA responses (45%–74%) and for measurable disease responses (11%–57%).23–27
Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): A trial of the Eastern cooperative oncology group
2012, Clinical Genitourinary Cancer
BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistant cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered by using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC).
Patients with metastatic CRPC received ixabepilone at 20 mg/m² intravenous weekly x 3, in 4-week cycles. This noncomparative study stratified patients to either a chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The primary endpoint was prostate-specific antigen response by using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints included radiographic response when using RECIST (Response Evaluation Criteria In Solid Tumors).
In total, 124 patients were enrolled, of whom, 109 were eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12 (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax, and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8 (20.5%), 12 (25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one patient on the CN and the TCx arm.
Ixabepilone was found to have an acceptable toxicity profile when administered by using a weekly schedule with less myelosuppression compared with prior studies when using the every 3-week schedule. Single-agent activity was observed and met prespecified activity levels for the Tax treated arm.

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Original ContributionWeekly Docetaxel in Elderly Patients with Prostate Cancer: Efficacy and Toxicity in Patients Aged ≥ 70 Years Compared with Patients Aged < 70 Years

Abstract

Hematol Oncol Clin North Am

Urology

Ann Oncol

Semin Oncol

Semin Oncol

Exploring the role of cancer centers for integrating aging and cancer research

Participation of patients 65 years of age or older in cancer clinical trials

J Clin Oncol

Chemotherapy for androgen-independent prostate cancer

Semin Urol Oncol

Pharmacology of Chemotherapy in the Older Cancer Patient

Cancer Control

Original Contribution
Weekly Docetaxel in Elderly Patients with Prostate Cancer: Efficacy and Toxicity in Patients Aged ≥ 70 Years Compared with Patients Aged < 70 Years