Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

Objective To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥ 8 (p = 0.004), an extent of disease value (EOD) of ≥ 2 (p = 0.004), and a 3-month PSA level > 1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. A 3-month PSA level > 1% of the pretreatment level was an independent predictor of OS (p = 0.004). Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level > 1% of the pretreatment level correlated with a poor prognosis.

Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.

Measurement of Proteasome Activity in Peripheral Blood Mononuclear Cells as an Indicator of Susceptibility to Bortezomib-Induced Severe Neurological Adverse Events in Patients with Multiple Myeloma

Aims: To explore the biomarker for predicting the occurrence of adverse events in myeloma patients treated by intravenous bortezomib, we measured proteasome activity in peripheral blood mononuclear cells. Methods: Samples were obtained from 34 bortezomib-naïve patients. Proteasome activity was measured at pre- and postchemotherapy phase by using a synthetic substrate. Results: Bortezomib injection resulted in a dramatic decrease in proteasome activity, reaching 32.4 ± 18.79% (mean ± SD) of the pretreatment level at 1 h, but it generally recovered at the end of the first course. In total, 6 patients manifested with severe bortezomib-induced peripheral neuropathy (sBIPN) in the second-third course. There was a nonsignificant trend for these patients to have lower levels of the relative proteasome activity at the end of the first course than those without sBIPN (median: 74.03 vs. 103.2%, p = 0.052). Moreover, in all of them, proteasome activity did not recover to the pretreatment level, whereas no patients with complete recovery manifested with sBIPN. Analysis with Fisher's exact test demonstrated that incomplete recovery of proteasome activity is a significant risk factor for sBIPN (p = 0.014). Conclusion: Patients with incomplete recovery of proteasome activity are at high risk for developing sBIPN, and the susceptible patients can be indicated by monitoring proteasome activity.

Predicting bortezomib-related severe neurologic adverse events by measuring proteasome activity in PBMCs.

8094 Background: Although a proteasome inhibitor bortezomib (BOR) is one of the backbone drugs for the treatment of multiple myeloma, severe neurologic adverse event (sNE) is a major obstacle for continuing the treatment. As there is no clinically available biomarker for predicting the occurrence of sNAE, we measured the proteasome activity (PrsAtv) in peripheral blood mononuclear cells (PBMCs). Methods: Patients (Pts) were treated by either standard Q3wks or weekly (BOR 1.3mg/m2: day 1, 8, 15, 22; Q5wks) schedule depending on physician’s decision. PBMCs were collected from 21 Pts and 99 healthy volunteers. Pts’ samples were collected before treatment, 1 hour after the 1st injection of BOR, and at the end of the 1st course. PrsAtv in PBMCs was measured by using a specific substrate SUC-LLVY-AMC, which becomes fluorescent upon cleavage by proteasome. Results: Levels of PrsAtv among volunteers were highly variable with no certain correlation with age and sex. Pretreatment levels of PrsAtv among Pts were also variable, and didn't correlate with the occurrence of sNAE. After 1 hour of BOR injection, PrsAtv decreased to 33.2±20.5% (mean ± SD) of the pretreatment level, and it generally recovered (112.5±77.6%) at the end of the 1st course. However, in 12 out of 21 Pts, it didn’t recover to ≥ 100%. Among these Pts, 5 manifested with sNAE (≥G3) during the 2nd or 3rd course of the chemotherapy. In a sharp contrast, no patients whose PrsAtv recovered to ≥100% manifested with sNAE. Pts who manifested with sNAE (5 Pts) showed the lower levels of PrsAtv at the end of the 1st course than those without sNAE (16 Pts) (67.4±11.8 vs 126.6±83.8%, p=0.075). It should be also strengthened that all the Pts who manifested with sNAE were treated by the standard Q3wks schedule, although levels of PrsAtv at the end of the 1st course were not significantly different between Q3 and Q5wks groups (109.0±68.3 vs 121.1±96.4 %, p=0.38). Contrary, there was no significant difference of the bortezomib response between these two treatment groups. Conclusions: Pts whose PrsAtv does not recover to ≥100% at the end of the 1st course are at high risk of manifesting with sNAE, and these Pts should not be treated by the standard Q3wks schedule in the subsequent courses.

Adalimumab Monotherapy in a Patient with Psoriatic Arthritis Associated with Chronic Renal Failure on Hemodialysis: A Case Report and Literature Review

We report a patient with psoriatic arthritis (PsA) who was successfully treated with adalimumab even while under hemodialysis therapy for associated chronic renal failure. Flow cytometry of circulating lymphocytes revealed an obvious decrease in both Th1 and Th17 cells after starting adalimumab. The latter returned to the pretreatment level in the course of adalimumab therapy, while the former did not. Adalimumab is a potent therapeutic option for PsA patients with chronic renal failure on hemodialysis, and Th1 in peripheral blood may reflect the disease activity.