Chemotherapy For Metastatic Prostate Cancer Research Articles

AlphaBet: A phase I/II trial evaluating the combination of radium-223 and [177Lu]Lu-PSMA-I&T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

TPS280 Background: [177Lu]Lu-PSMA-I&T (LuPSMA) is a small molecule radioligand that delivers radiation via beta-particulate emission to cells expressing prostate-specific membrane antigen (PSMA). Despite a survival benefit in mCRPC, responses for many are not durable, with the majority of pts developing progressive osseous disease. Due to the lack of crossfire radiation in micrometastatic disease, small cancer cell clusters in the bone marrow may not receive an adequate dose of radiation from 177Lu to induce cytotoxic double-stranded DNA breaks. Alpha-emitters have a shorter path length (≤100 µm) and higher linear energy transfer, making them better suited for treating micrometastatic disease. As a calcium-mimetic, radium-223 (223Ra) is a bone-specific alpha-emitter which targets osteoblastic bone metastases. We hypothesise that the combination of LuPSMA with 223Ra will be well tolerated and lead to improved response durability. Methods: This phase I/II, single-arm, single-centre study will enrol 36 patients with mCRPC who have progressed on a prior second-generation antiandrogen. Up to 6 cycles of LuPSMA (7.4 GBq) and 223Ra (28 kBq/kg - 55 kBq/kg) will be given intravenously every 6 weeks, along with background androgen deprivation and bone protective therapy. Key eligibility criteria include a diagnosis of mCRPC with at least two untreated bone metastases visible on bone scintigraphy and PSMA-positive disease on PSMA PET/CT (SUVmax ≥20). Sites of FDG-positive disease must be either PSMA-positive or have increased uptake on bone scan. Other eligibility criteria include an ECOG status of 0-2, and adequate bone marrow and organ function. Patients treated with more than one line of chemotherapy for metastatic prostate cancer are not eligible. Blood samples and biopsies will be taken at baseline, on treatment, and at progression to develop tumor- and immune-based biomarkers that predict treatment response and associated survival benefit. A traditional 3+3 dose-escalation model will be utilized initially, escalating the dose of 223Ra. The dose of LuPSMA will remain fixed. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with LuPSMA, and the 50% PSA response rate. Secondary objectives include measuring the frequency and severity of adverse events, assessment of efficacy through overall, radiographic and PSA progression-free survival, overall survival, objective tumor response rate, and evaluation of pain and health-related quality of life. Enrolment commenced in September 2022 and will continue for 24 months. Clinical trial information: NCT05383079 .

Changes in neutrophile-to-lymphocyte ratio as predictive and prognostic biomarker in metastatic prostate cancer treated with taxane-based chemotherapy

ObjectivesTo assess the predictive and prognostic value of changes in longitudinal neutrophile-to-lymphocyte (NLR) ratios in men receiving taxane-based chemotherapy for metastatic prostate cancer (PC).MethodsRetrospective, unicentric cohort study of patients treated with either docetaxel for metastatic hormone-sensitive PC (mHSPC) or docetaxel or cabazitaxel for metastatic castration-refractory PC (mCRPC) at a tertiary referral hospital between 2010 and 2019. NLR ratios were calculated for each cycle. Next, slopes over the first three (NLR3) and over six cycles (NLR6) were calculated and analysed for biochemical/radiologic response and survival.ResultsA total of 36 mHSPC (docetaxel), 118 mCRPC (docetaxel) and 38 mCRPC (cabazitaxel) patients were included. NLR3 was significantly associated with 1-year-survival, radiographic and biochemical response in mCRPC (docetaxel) in uni- and multivariable analyses. In mCRPC (docetaxel), positive NLR3s were associated with favourable 1-year-survival.ConclusionThis study demonstrated NLR3 as a prognostic marker in men receiving docetaxel for mCRPC. NLR3 might be a clinical tool to reflect the individual’s response to taxane-based chemotherapy. Thereby, NLR3 could complement existing biomarkers and help to early identify treatment failure before complications arise. Further prospective and multicentric studies are needed to extend and confirm the presented results.

The role of chemotherapy in metastatic prostate cancer.

To summarize the role of chemotherapy and offer some guidance regarding the selection of chemotherapy in mPC. Patients with mHSPC have varied prognoses with testosterone suppression alone (androgen deprivation therapy, ADT) and differential responses to docetaxel with ADT. Patients with de novo and metachronous high-volume disease have a robust survival benefit with the addition of docetaxel to hormonal therapies. Patients with synchronous low-volume disease have a more modest survival benefit from docetaxel and there is no evidence of survival benefit with docetaxel in patients with metachronous low-volume disease. Integration of biomarkers may refine treatment selection regardless of volume of disease. Docetaxel and cabazitaxel also impart an OS benefit in patients with metastatic castration-resistant prostate cancer (mCRPC). The choice of chemotherapy in mCRPC depends on treatment received in mHSPC setting. Docetaxel remains the first line chemotherapy in castration-resistant patients who have not received it in mHSPC followed by cabazitaxel, otherwise cabazitaxel can be deployed without docetaxel retreatment. Chemotherapy is a key class of therapy for selected patients with mHSPC and mCRPC.

Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups.

No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void. We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014-2015). Separate and specific Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed. Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63-0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54-1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73-1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11-0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group. Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities.

A0526 - Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups

A0526 - Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups

68Ga-PSMA PET/CT for Response Assessment and Outcome Prediction in Metastatic Prostate Cancer Patients Treated with Taxane-Based Chemotherapy.

We aimed to evaluate the role of PET targeting the prostate-specific membrane antigen (PSMA) for response assessment in metastatic prostate cancer (PCa) patients treated with taxane-based chemotherapy (docetaxel or cabazitaxel) and its predictive value on patient outcome. Methods: We retrospectively evaluated 37 patients with metastatic hormone-sensitive PCa or metastatic castration-resistant PCa (mCRPC) who underwent 68Ga-PSMA-11 PET/CT at baseline and after the last cycle of taxane-based chemotherapy (docetaxel or cabazitaxel) without treatment modification between scans. Biochemical response (BR) was defined as an undetectable or at least 50% decreased level of prostate-specific antigen, compared with baseline. Associations between BR and different PET parameters were tested. A cutoff of at least a 30% decrease in PSMA total tumor volume (PSMA-TV) was used to define a PSMA response (PSMA-R) versus a PSMA nonresponse (PSMA-NR). Correlations between PSMA PET/CT response and BR were evaluated using the ϕ-coefficient. Associations between PET response and overall survival (OS) was tested using Cox regression and the Kaplan-Meier method. Results: Our cohort comprised 8 (22%) metastatic hormone-sensitive PCa and 29 (78%) mCRPC patients. Twenty-one patients received docetaxel treatment, and 16 received cabazitaxel (median, 6 cycles; interquartile range, 5-8 cycles). BR was found in 18 of 37 patients. Using PSMA total tumor volume, PSMA PET/CT response was concordant with BR in 35 of 37 patients (ϕ = 0.89, P < 0.0001). Eighteen of 37 patients had PSMA-R (6, complete response; 12, partial response), and 19 had PSMA-NR (17, progressive disease; 2, stable disease). After a median follow-up of 23 mo, there was a statistically significant longer OS for PSMA-R than for PSMA-NR (median OS not reached vs. 12 mo, respectively; hazard ratio, 0.10; 95% CI, 0.03-0.39; P = 0.001) for the entire population. Among the mCRPC subgroup, differences in OS were also observed (median, 22 vs. 12 mo, respectively; hazard ratio, 0.22; 95% CI, 0.06-0.82; P = 0.023), with a 12-mo OS rate of 100% for PSMA-R and 52% for PSMA-NR (P = 0.011). Conclusion: This retrospective analysis suggests that 68Ga-PSMA-11 PET/CT is a promising imaging modality for assessing response to taxane-based chemotherapy in metastatic PCa. Changes in PSMA expression might be used as a predictive biomarker for OS to help tailor individual therapy and select eligible patients for clinical trials.

Docetaxel Treatment for Metastatic Hormone-sensitive Prostate Cancer in Daily Practice

BackgroundCurrently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations. ObjectiveWe aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice. Design, setting, and participantsIn this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records. Outcome measurements and statistical analysisWe compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice. Results and limitationsDespite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%). ConclusionsEarly docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment. Patient summaryWe studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.

Improvement in overall and cancer-specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients.

Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001). In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.

In vivo CRISPR/Cas9 knockout screen: TCEAL1 silencing enhances docetaxel efficacy in prostate cancer.

Docetaxel chemotherapy in metastatic prostate cancer offers only a modest survival benefit because of emerging resistance. To identify candidate therapeutic gene targets, we applied a murine prostate cancer orthograft model that recapitulates clinical invasive prostate cancer in a genome-wide CRISPR/Cas9 screen under docetaxel treatment pressure. We identified 17 candidate genes whose suppression may enhance the efficacy of docetaxel, with transcription elongation factor A-like 1 (Tceal1) as the top candidate. TCEAL1 function is not fully characterised; it may modulate transcription in a promoter dependent fashion. Suppressed TCEAL1 expression in multiple human prostate cancer cell lines enhanced therapeutic response to docetaxel. Based on gene set enrichment analysis from transcriptomic data and flow cytometry, we confirmed that loss of TCEAL1 in combination with docetaxel leads to an altered cell cycle profile compared with docetaxel alone, with increased subG1 cell death and increased polyploidy. Here, we report the first in vivo genome-wide treatment sensitisation CRISPR screen in prostate cancer, and present proof of concept data on TCEAL1 as a candidate for a combinational strategy with the use of docetaxel.

Re: Platinum-based Chemotherapy in Metastatic Prostate Cancer with DNA Repair Gene Alterations

Re: Platinum-based Chemotherapy in Metastatic Prostate Cancer with DNA Repair Gene Alterations

Early Chemotherapy in Metastatic Prostate Cancer Improves Survival: a Quick Note to Surgical Colleagues

Metastatic prostate cancer is a hormone sensitive cancer. For patients with prostate cancer, general surgeons and urologists are the points of first contact. Historically, restricted treatment options meant that such patients were started on, and continued hormonal therapy with them. Chemotherapy is started once these tumours became hormone-refractory, with limited survival benefits. However, three recently published randomized, Phase III trials (GETUG-AFU15, CHAARTED, STAMPEDE) have provided Level I evidence that upfront chemotherapy in hormone sensitive metastatic prostate cancer dramatically improves survival, especially in those with heavy volume disease (an increase of up to 22 months). The authors recommend that general surgeons and urologists discuss patients in multi-disciplinary tumour boards so that fit patients can receive the benefits of upfront chemotherapy.

Platinum-Based Chemotherapy in Metastatic Prostate Cancer With DNA Repair Gene Alterations.

Alterations in DNA damage repair (DDR) genes occur in up to 25% of patients with metastatic castration-resistant prostate cancer (mCRPC) and may sensitize to platinum chemotherapy. We aimed to evaluate the efficacy of platinum-based chemotherapy in DDR-mutant (DDRmut) mCRPC. We assessed response to platinum chemotherapy based on DDR gene alteration status in men with mCRPC who underwent tumor and germline genomic profiling. Patients with deleterious alterations in a gene panel that included BRCA2, BRCA1, ATM, PALB2, FANCA, and CDK12 were considered DDRmut. A total of 109 patients with mCRPC received platinum-based chemotherapy between October 2013 and July 2018. Sixty-four of 109 patients were taxane refractory and poly (ADP-ribose) polymerase inhibitor (PARPi) naïve. Within this subset, DDRmut was found in 16/64 patients (25%) and was associated with an increased likelihood of achieving a prostate-specific antigen (PSA) decline of 50% or more from baseline (PSA50; odds ratio, 7.0; 95% CI, 1.9 to 29.2). Time on platinum chemotherapy tended to be longer in the DDRmut group (median, 3.0 v 1.6 months; hazard ratio, 0.55, 95% CI, 0.29 to 1.24). No difference in survival was detected. Of 8 patients with DDRmut disease who received platinum-based therapy after a PARPi, 3/7 evaluable patients had radiographic partial response or stable disease, and 2/7 had a PSA50 response. None of 4 patients with ATM mutations had platinum responses regardless of prior PARPi exposure. Patients with DDRmut disease had better response to platinum-based chemotherapy, suggesting that DDR status warrants prospective validation as a potential biomarker for patient selection. Responses to platinum chemotherapy were observed in BRCA-altered prostate cancer after PARPi progression. Additional studies are needed to determine the predictive role of individual genes on platinum sensitivity in the context of other clinical and genomic factors.

Platinum-based chemotherapy in metastatic prostate cancer with alterations in DNA damage repair genes.

5038 Background: Platinum-based chemotherapy has shown palliative and radiographic benefit in small unselected studies of metastatic castration-resistant prostate cancer (mCRPC). Alterations in DNA damage repair genes (DDRmut), which occur in ~25% of patients with mCRPC, may sensitize to platinum-based chemotherapy, and may aid in the selection of patients for this therapy. We sought to evaluate the efficacy of platinum-based chemotherapy in DDRmut mCRPC. Methods: We performed a retrospective review of patients with prostate cancer who underwent tumor genomic profiling and received platinum-based chemotherapy. Deleterious alterations in a panel including BRCA2, BRCA1, ATM, FANCA, CDK12 or PALB2 were classified as DDRmut. Absence of deleterious alterations in those genes was classified as DDRwt. MSI-H cases were excluded from analysis. Electronic charts, PSA values, and scans were reviewed to assess for outcomes. Results: From October 2013 to July 2018, 109 patients with mCRPC received platinum-based chemotherapy. 64/109 had prior taxane progression and were PARP inhibitor (PARPi) naïve at the time of platinum-based chemotherapy. DDRmut was found in 16/64 (25%) of patients ( BRCA2, n = 6; ATM, n = 2; CDK12, n = 4; FANCA, n = 4; PALB2, n = 1). Visceral metastasis occurred in 4/16 (25%) of DDRmut patients and in 22/48 (46%) of DDRwt patients. PSA50 responses were more common among DDRmut (8/15 evaluable = 53%, 95% CI, 30-75%) than among DDRwt patients (5/42 evaluable = 12%, 95% CI, 5-25%). Time on platinum-based chemotherapy tended to be longer in the DDRmut group (median 3.1 vs 1.8 months; HR 0.73, 95% CI 0.42-1.26). Of 8 DDRmut patients ( BRCA2, n = 6; BRCA1, n = 1; ATM, n = 2) who received platinum-based chemotherapy after progression on a PARPi, 3/7 evaluable patients (43%) had RECIST response or stable disease, and 2/7 evaluable patients (29%) had a PSA50 response. Of 4 patients with ATM deleterious mutations, none had a radiographic or PSA50 response to platinum-based chemotherapy. Conclusions: Platinum-based chemotherapy showed activity in DDRmut mCRPC patients before and after PARPi treatment.

Serum Free Methylated Glutathione S-transferase 1 DNA Levels, Survival, and Response to Docetaxel in Metastatic, Castration-resistant Prostate Cancer: Post Hoc Analyses of Data from a Phase 3 Trial

BackgroundGlutathione S-transferase 1 (GSTP1) expression is inactivated in >90% of all prostate cancers in association with aberrant DNA methylation. Detection of serum free methylated GSTP1 (mGSTP1) DNA is associated with overall survival (OS) and response to docetaxel in metastatic castration-resistant prostate cancer (mCRPC) in test and internal validation cohorts. ObjectiveTo assess the relationship between serum free mGSTP1 and treatment outcomes in SYNERGY, a phase 3 multicentre randomised trial testing the addition of custirsen to first-line chemotherapy with docetaxel in mCRPC. Design, setting, and participantsSerum free mGSTP1 DNA was measured by a sensitive methylation-specific polymerase chain reaction assay in paired samples (baseline and after two cycles of docetaxel) from 600 patients. Outcome measurements and statistical analysisAssociations between serum free mGSTP1 at baseline, change in mGSTP1 after docetaxel, OS, and time to prostate-specific antigen (PSA) progression were examined using Cox proportional hazards models and Kaplan-Meier methods. Results and limitationsSerum free mGSTP1 was detectable at baseline in 458 (81%) patients. Of those with detectable mGSTP1 at baseline, mGSTP1 became undetectable after two cycles in 243 (53%). Undetectable mGSTP1 at baseline was associated with longer OS (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.29–0.55; p<0.00001). The event of mGSTP1 becoming undetectable after two cycles of chemotherapy was associated with longer OS (HR 0.36, 95% CI 0.29–0.46; p<0.00001) and longer time to PSA progression (HR 0.44, 95% CI 0.35–0.56; p<0.00001). Associations between mGSTP1 and clinical outcomes were independent of other established prognostic variables. Analysis was limited by the lack of radiographic progression-free survival data. ConclusionsThis is the first study to externally validate the prognostic role of a circulating epigenetic biomarker in mCRPC. Further studies are needed to validate serum free mGSTP1 as a surrogate endpoint for clinical trials and as a potential clinical decision tool. Patient summaryIn this study, we confirmed that a blood marker predicted outcomes after chemotherapy for metastatic prostate cancer. This marker may accelerate future clinical trials of new therapies and be useful in the clinic to guide treatment decisions.

A Cost-Utility Analysis Comparing Two Sequences of Treatment for First-Line Chemotherapy in Metastatic Prostate Cancer (MCRPC): Cabazitaxel Followed by Docetaxel Versus Docetaxel Followed by Cabazitaxel

A Cost-Utility Analysis Comparing Two Sequences of Treatment for First-Line Chemotherapy in Metastatic Prostate Cancer (MCRPC): Cabazitaxel Followed by Docetaxel Versus Docetaxel Followed by Cabazitaxel

Targeted hydroxyethyl starch prodrug for inhibiting the growth and metastasis of prostate cancer

Prostate cancer is one of the most prevalent malignancies among men. Although chemotherapy has been an effective therapeutic approach for treating metastatic prostate cancer, serious undesired side effects have hampered its wide application clinically. In this work, a pH-responsive LHRH-conjugated hydroxyethyl starch-doxorubicin (HES-DOX/LHRH) prodrug was facilely synthesized by conjugating oxidized HES (HES-CHO) with DOX and LHRH through an acid-sensitive Schiff base bond. The resulting prodrug spontaneously self-assembled into nanoscopic micelle with a radius of about 55nm in an aqueous environment. HES-DOX/LHRH significantly improved the invivo tissue distribution of the drug. Compared to its non-targeted counterpart, targeted HES-DOX/LHRH demonstrated a greater invitro anti-proliferative capability toward mouse RM-1 prostate cells. More importantly, targeted HES-DOX/LHRH exhibited higher levels of anti-tumor and anti-metastasis activities against an RM-1-xenografted mouse model, with lower systemic toxicity compared to free DOX·HCl and non-targeted HES-DOX. Hence, these results revealed that targeted HES-DOX/LHRH possesses great potential application in clinical chemotherapy of metastatic prostate cancer.

Using the SAEM algorithm for mechanistic joint models characterizing the relationship between nonlinear PSA kinetics and survival in prostate cancer patients.

Joint modeling is increasingly popular for investigating the relationship between longitudinal and time-to-event data. However, numerical complexity often restricts this approach to linear models for the longitudinal part. Here, we use a novel development of the Stochastic-Approximation Expectation Maximization algorithm that allows joint models defined by nonlinear mixed-effect models. In the context of chemotherapy in metastatic prostate cancer, we show that a variety of patterns for the Prostate Specific Antigen (PSA) kinetics can be captured by using a mechanistic model defined by nonlinear ordinary differential equations. The use of a mechanistic model predicts that biological quantities that cannot be observed, such as treatment-sensitive and treatment-resistant cells, may have a larger impact than PSA value on survival. This suggests that mechanistic joint models could constitute a relevant approach to evaluate the efficacy of treatment and to improve the prediction of survival in patients.

Optimum Timing of Chemotherapy for Metastatic Prostate Cancer

Optimum Timing of Chemotherapy for Metastatic Prostate Cancer

Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: a retrospective review.

BackgroundDocetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy.MethodsWe conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed.ResultsObese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel.ConclusionObese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.

Does the hurria/CARG tool or VES-13 predict grade 3+ toxicities in men undergoing chemotherapy for metastatic prostate cancer?

Track 1 Solid Tumours in the Elderly Prostate, bladder, kidney cancer in eldery patients P027 Does the hurria/CARG tool or VES-13 predict grade 3+ toxicities in men undergoing chemotherapy for metastatic prostate cancer? S. Alibhai*, T. Manokumar, S. Aziz, F. Rizvi, H. Breunis, H. Gulamhusein, N. Timilshina, I. Tannock, A. Joshua. Princess Margaret Cancer Centre; University of Toronto; University Health Network, Toronto, Canada