Metastatic Castration-resistant Cancer Research Articles

Phase 1/2 study of ADXS31-142 alone and in combination with pembrolizumab in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC): The KEYNOTE-046 trial

Phase 1/2 study of ADXS31-142 alone and in combination with pembrolizumab in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC): The KEYNOTE-046 trial

PARP Inhibition in Advanced Prostate Cancer

Although much of the recent progress in managing metastatic castration-resistant prostate cancer (mCRPC) is based on targeting the androgen receptor,

Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis.

Conflicting evidence exists regarding the beneficial effects of metformin in prostate cancer. To determine the association between metformin and clinical outcomes in prostate cancer using systematic review and meta-analysis. Original articles published in English until third week of July, 2014 were searched in electronic databases (Medline-Ovid, Scopus, The Cochrane Library, Web of Science, ProQuest) for studies on metformin use in prostate cancer. The clinical outcomes assessed were: development of biochemical recurrence, metastases or castration-resistant metastatic cancer, all-cause and prostate cancer-specific mortality. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I2 statistics. Sensitivity analysis was conducted to assess the robustness of findings and publication bias was assessed by the Egger's regression asymmetry test and contour plot. Out of 230 retrieved citations, eight retrospective cohort studies and one nested-case-control study met the inclusion criteria. Metformin use was marginally associated with reduction in the risk of biochemical recurrence (pHR: 0.82, 95% CI: 0.67, 1.01, P-value=0.06, I2=25%, five studies). Metformin use was not significantly associated with metastases (pHR: 0.59, 95% 0.30-1.18, P-value=0.14, I2=74%, three studies), all-cause mortality (pHR: 0.86; 95% CI, 0.67, 1.10, P-value=0.23, I2: 73%, six studies) and prostate cancer-specific mortality (pHR: 0.76, 95% CI: 0.43, 1.33, P-value = 0.33, I2=60%, four studies). Pooled estimates for all outcomes varied in sensitivity analysis by diabetes status and primary treatment of prostate cancer. Systematic review revealed mixed findings on metformin use and the risk of CRPC. Metformin may reduce the risk of biochemical recurrence in prostate cancer. Given the potential of selection bias in the observational studies, randomized trials should be designed to assess the efficacy of metformin use in prostate cancer.

Circulating tumor cells (CTCs) and LDH as prognostic factors in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or following docetaxel treated in the orteronel phase 3 ELM-PC 5 trial.

5014 Background: Results from a global phase 3 study demonstrated that orteronel 400 mg BID /prednisone 5 mg (O+P), vs placebo/prednisone alone (P), improved radiographic progression (rPFS) and inc...

Long-term efficacy of the treatment for metastatic castration-resistant prostate cancer

Objective To:investigate the role of docetaxel and prednisone on treating metastatic castration-resistant prostate cancer (mCRPC),and to report the long-term efficacy.Methods From July 2005 to March 2012,299 mCRPC patients were nonrandomised into two groups.Docetaxel (75 mg/m2) and prednisone (5 mg,bid) were given to patients in Group A,with a chemotherapy cycle of three-week.And the other patients in group B were treated with endocrine therapy,radiotherapy,traditional Chinese medicine,and so on.102 cases were nonrandomised into group A,with age range from 50 to 86 years (median 72 years),tPSA range from 9.9 μg/L to 5000.0 μg/L (median 94.0 μg/L),Gleason score range from 6 to 10 (median 7),pain score range from 0 to 7 (median 2),bone metastasis in 98 cases,lung metastasis in 1 1 cases,liver metastasis in 5 cases,lymph node metastasis in 19 cases,and the time from prostate cancer diagnosis to mCRPC range from 5.4 months to 123.2 months (median 18.6 months).The tPSA,pain score,bone scan,and metastatic focuses before and after chemotherapy were compared.197 patients were nonrandomised in group B,with age range from 54 to 85 years (median 73 years),tPSA range from 5.4 μg/L to 1270.0 μg/L (median 71.0 μg/L),Gleason score range from 6 to 10 (median 7),pain score range from 0 to 4 (median 2),bone metastasis in 176 cases,lung metastasis in 17 cases,liver metastasis in 6 cases,lymph node metastasis in 43 cases,and the time from prostate cancer diagnosis to mCRPC range from 6.0 months to 137.1 months (median 18.4 months).SPSS (v10.0),t and x2 analysis are used to evaluate the baseline differences between the 2 groups,and Kaplan-Meier survival curves are used to evaluate the overall survival between the two groups.Results There is no difference between the two group on baseline.In group A,100-170 milligram docetaxel were given for each cycle,1-12 cycles were experienced.The PSA responses were excellent in 59 cases (57.8％),effective in 21 cases (20.6％),useless in 22 cases (21.6％),and PSA response ratio was 78.4％ (80 cases).98 patients were suffered from bone metastasis.Bone scan improved in 33 cases (33.7％),stable in 47 cases (48.0％),progressed in 18 cases (18.4％).There are 11 cases with lung metastasis,improved in 5 cases (45.5％),progressed in 3 cases (27.3％),and stable in other cases after chemotherapy.There are 5 cases with liver metastasis,improved in 1 case,progressed in 4 cases.Among 19 N1 cases,lymph nodes diminished in 5 cases (26.3％),enlarged in 2 case (10.5％) and stable in 12 cases (63.2％) after chemotherapy.Pain scores were decreased in 38 cases (37.3％),increased in 27 cases (26.5％),and no different in 37 cases (36.3％).The median overall survival in group A is 28.3 months,and 23.9 months in group B.Extra median 4.4 months survival benefit is showed in group A.The common adverse events were myelosuppression,alopecia,fatigue,numbness in the end of limbs,nail changes,phlebitis.Conclusions Docetaxel combined with prednisone for the treatment of mCRPC can delay the progression of the disease,prolong the overall survival,decrease the PSA value,diminish the metastatic focuses,ease the pain,improvc thc quality of lifc,and thc tolcrance is quite good. Key words: Prostate cancer; Chemotherapy; Docetaxel; Prednisone

Survival analysis of patients with metastatic castration-resistant prostate cancer treated with docetaxel plus prednisone

Objective To explore the potential value of patient characteristics in predicting overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel plus prednisone.Methods We retrospectively analyzed the data of 115 consecutive Chinese patients with mCRPC received docetaxel chemotherapy in our institution from Nov.2005 to Sep 2011.The median age at diagnosis was 65 years old and median serum prostate-specific antigen (PSA) level at diagnosis was 100.0 μg/L.The Gleason score≤7 in 26 patients and ≥8 in 89 patients.The median age at chemotherapy was 68 years old,ranging from 51 to 82 years old.The median baseline PSA level was 90.5 μg/L,ranging from 0.8 to 4066.4 μg/L.The median baseline hemoglobin (Hb) concentration was 121 g/L and median baseline alkaline phosphatase (ALP) concentration was 110 U/L.The time to castration resistance ranged from 2 to 114 months and the median value was 23.All 115 patients have bone metastasis,and 16 cases were simultaneously observed the presence of visceral metastasis including lung (9 cases),bladder (4 cases),liver (2 cases) and brain (1 case).The average cycles of chemotherapy was 6,ranging from 1 to 16.We retrospectively collected the variables including patient characteristics at diagnosis and characteristics before the chemotherapy.All laboratory analyses were performed in the same laboratory.Survival analysis was performed using KaplanMeier curves,and the differences in overall survival rates were assessed using the log-rank test.Only variables that were statistically significant in the univariate analysis (P＜0.05) were included in the multivariate model.Results The follow-up was performed until April 30,2012,and median follow-up time was 45 months,ranging from 2 to 74 months.During the follow-up period,87 of 115 patients (75.7％) died and the median OS for the entire cohort was 17 months,ranging from 2 to 46 months.The univariate analysis identified a total of 8 statistically significant predictors of OS:baseline serum PSA level,baseline Hb concentration,baseline ALP concentration,baseline lactate dehydrogenase (LDH) concentration,baseline gamma-glutamyl transpeptidase (GGT) concentration,ECOG PS,time to castration resistance and cycles of chemotherapy.Subsequent multivariate analysis reserved baseline ALP≥110 U/L,baseline Hb＜110 g/L,time to castration resistance＜23 months and cycles of chemotherapy＜6 as independent prognostic factors for shorter OS.Conclusions This retrospective analysis has demonstrated that baseline ALP concentration,baseline Hb concentration,time to castration resistance and cycles of chemotherapy could provide independent prognostic information of OS in Chinese patients with mCRPC treated with docetaxel plus prednisone. Key words: Castration-resistant prostate cancer; Docetaxel; Prognosis ; ALP ; Time to castration resistance

Single‐cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT‐related genes in metastatic prostate cancer

Prostate tumors shed circulating tumor cells (CTCs) into the blood stream. Increased evidence shows that CTCs are often present in metastatic prostate cancer and can be alternative sources for disease profiling and prognostication. Here we postulate that CTCs expressing genes related to epithelial-mesenchymal transition (EMT) are strong predictors of metastatic prostate cancer. A microfiltration system was used to trap CTCs from peripheral blood based on size selection of large epithelial-like cells without CD45 leukocyte marker. These cells individually retrieved with a micromanipulator device were assessed for cell membrane physical properties using atomic force microscopy. Additionally, 38 CTCs from eight prostate cancer patients were used to determine expression profiles of 84 EMT-related and reference genes using a microfluidics-based PCR system. Increased cell elasticity and membrane smoothness were found in CTCs compared to noncancerous cells, highlighting their potential invasiveness and mobility in the peripheral circulation. Despite heterogeneous expression patterns of individual CTCs, genes that promote mesenchymal transitioning into a more malignant state, including IGF1, IGF2, EGFR, FOXP3, and TGFB3, were commonly observed in these cells. An additional subset of EMT-related genes (e.g., PTPRN2, ALDH1, ESR2, and WNT5A) were expressed in CTCs of castration-resistant cancer, but less frequently in castration-sensitive cancer. The study suggests that an incremental expression of EMT-related genes in CTCs is associated with metastatic castration-resistant cancer. Although CTCs represent a group of highly heterogeneous cells, their unique EMT-related gene signatures provide a new opportunity for personalized treatments with targeted inhibitors in advanced prostate cancer patients.

Erratum

Erratum

Immunotherapy for Castration-Resistant Prostate Cancer: A New Era?

Men with metastatic castration-resistant prostate cancer (CRPC) typically survive about 1 to 2 years after progression on hormonal therapy. Until 2010,