Dataset Information

Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.

ABSTRACT: We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression.Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine levels with lenalidomide treatment effect. Estimates were obtained using generalized estimating equations. Changes in circulating anti-prostate antibodies were evaluated using a high-throughput immunoblot technique.Treatment with lenalidomide was associated with global changes in immunoreactivity to a number of prostate-associated antigens, as well as with changes in circulating levels of the T(H) 2 cytokines IL-4, IL-5, IL-10, and IL-13. Disease progression in treated patients was associated with an increase in circulating IL-8 levels, while IL-8 levels decreased significantly in non-progressors.Lenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti-prostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL-8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials.

SUBMITTER: Zabransky DJ

PROVIDER: S-EPMC3248613 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.

Zabransky Daniel J DJ Smith Heath A HA Thoburn Christopher J CJ Zahurak Marianna M Keizman Daniel D Carducci Michael M Eisenberger Mario A MA McNeel Douglas G DG Drake Charles G CG Antonarakis Emmanuel S ES Antonarakis Emmanuel S ES

The Prostate 20110711 5

<h4>Background</h4>We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression.<h4>Methods</h4>Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine level ...[more]

PMID: 21748755

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Project description:New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro.In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000 mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen.The cohort (n = 14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000 mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P = 0.17). No patients experienced a maintained decline in serum PSA from baseline.These data suggest that 4,000 mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500 mg) and high-dose (4,000 mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial.

Project description:BackgroundPhase 2 trial endpoints that can be utilized in high-risk biochemical recurrence (BCR) after prostatectomy as a way of more rapidly identifying treatments for phase 3 trials are urgently needed. The efficacy of abiraterone acetate plus prednisone (AAP) in BCR is unknown.ObjectiveTo compare the rates of complete biochemical responses after testosterone recovery after 8 mo of AAP and degarelix, a gonadotropin-releasing hormone antagonist, alone or in combination.Design setting and participantsPatients with BCR (prostate-specific antigen [PSA] ≥1.0 ng/ml, PSA doubling time ≤9 mo, no metastases on standard imaging, and testosterone ≥150 ng/dl) after prostatectomy (with or without prior radiotherapy) were included in this study.InterventionPatients were randomized to AAP (arm 1), AAP with degarelix (arm 2), or degarelix (arm 3) for 8 mo, and monitored for 18 mo.Outcome measurements and statistical analysisThe primary endpoint was undetectable PSA with testosterone >150 ng/dl at 18 mo. Secondary endpoints were undetectable PSA at 8 mo and time to testosterone recovery.Results and limitationsFor the 122 patients enrolled, no difference was found between treatments for the primary endpoint (arm 1: 5.1% [95% confidence interval {CI}: 1-17%], arm 2: 17.1% [95% CI: 7-32%], arm 3: 11.9% [95% CI: 4-26%]; arm 1 vs 2, p = 0.93; arm 2 vs 3, p = 0.36). AAP therapy showed the shortest median time to testosterone recovery (36.0 wk [95% CI: 35.9-36.1]) relative to degarelix (52.9 wk [95% CI: 49.0-56.0], p < 0.001). Rates of undetectable PSA at 8 mo differed between AAP with degarelix and degarelix alone (p = 0.04), but not between AAP alone and degarelix alone (p = 0.12). Limitations of this study include a lack of long-term follow-up.ConclusionsRates of undetectable PSA levels with testosterone recovery were similar between arms, suggesting that increased androgen suppression with AAP and androgen deprivation therapy (ADT) is unlikely to eradicate recurrent disease compared with ADT alone.Patient summaryWe evaluated the use of abiraterone acetate plus prednisone (AAP) and androgen deprivation therapy (ADT), AAP alone, or ADT alone in men with biochemically recurrent, nonmetastatic prostate cancer. While more men who received the combination had an undetectable prostate-specific antigen (PSA) level at 8 mo on treatment, once men came off treatment and testosterone level rose, there was no difference in the rates of undetectable PSA levels. This suggests that the combination is not able to eradicate disease any better than ADT alone.

Dataset Information

Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.

Publications

Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.

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