Clinical variables associated with overall survival in metastatic castration resistant prostate cancer (mCRPC) patients treated with sipuleucel-T immunotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16565-e16565
Author(s):  
Xiao Wei ◽  
Jaselle Perry ◽  
Emily Chang ◽  
Li Zhang ◽  
Robert A. Hiatt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Performance Status ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Prior Chemotherapy ◽  
Ecog Ps ◽  
Baseline Psa

e16565 Background: Sipuleucel-T (Sip-T) is a cellular-based cancer immunotherapy for men with asymptomatic or minimally symptomatic mCRPC. Its approval was based on overall survival (OS) benefit in randomized placebo-controlled phase 3 trials. However, treatment was associated with PSA decline in only a small minority of pts. Understanding clinical factors predictive of OS may help to guide treatment decisions, including pt selection and timing of Sip-T relative to other therapies. Methods: This is a retrospective chart review of mCRPC pts treated with Sip-T at UCSF between April 2010 and April 2016. All pts completed 3 Sip-T infusions. Patients with localized prostate cancer treated with neoadjuvant Sip-T (NCT00715104) and pts with mCRPC treated with an ongoing phase 2 Sip-T/Ipilimumab trial (NCT01804465) were excluded. Kaplan-Meier method was used to estimate OS. The predictive value of candidate variables – including age, ECOG performance status (PS), Gleason score, metastatic volume, baseline PSA, baseline PSADT, prior abiraterone or enzalutamide, and prior chemotherapy – was assessed using univariate and multivariate Cox proportional hazard model. Results: Of 43 patients evaluated to date, 74.4% had ECOG PS 0, 88.4% had bone +/- nodal metastasis, 81.4% had low metastatic volume, 9.3% had prior abiraterone, 2.3% had prior enzalutamide, and 9.3% had prior chemotherapy. The median age was 69 years (range 53-85), median baseline PSA was 8.3 ng/mL (range 0.05-227.9) and median PSA doubling time (PSADT) was 3.9 mo (range 1.4-15.1). At a median follow-up of 21.4 mo, the median OS was 34.1 mo (95% CI 25.7-41.4). Univariate analysis showed that ECOG PS (HR 6.66, p < 0.001) and PSA (log-transformed) (HR 3.36, p = 0.002) were significantly associated with OS. There was a trend towards worse OS with faster baseline PSADT (log-transformed) (HR 0.16, p = 0.11) and prior chemotherapy (HR = 4.13, p = 0.11). By multivariate analysis, ECOG PS, baseline PSA and baseline PSADT were statistically significant (p < 0.05). Conclusions: In this ongoing retrospective cohort, ECOG PS, baseline PSA and baseline PSADT were associated with OS in mCRPC patients treated with Sip-T.

Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Independent Predictor ◽  
Performance Status ◽  
Univariate Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]

Clinical versus radiographic progression and overall survival for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) from COU-AA-302.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 193-193 ◽  
Author(s):  
Charles J. Ryan ◽  
Thian Kheoh ◽  
Howard I. Scher ◽  
Peter De Porre ◽  
Margaret K. Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Radiographic Progression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
End Points ◽  
Ecog Ps

193 Background: COU-AA-302 evaluated abiraterone acetate plus prednisone (AA) vs prednisone (P) in chemotherapy-naïve mCRPC pts, with overall survival (OS) and radiographic progression-free survival (rPFS) as co-primary end points. Per study criteria, pts with radiographic progression (RAD) only were allowed to continue treatment, while those with unequivocal clinical progression (UCP) only were not, and were censored for rPFS. We evaluated the clinical significance of survival outcomes for pts with UCP only vs RAD only from the prospective COU-AA-302 trial. Methods: UCP was defined per protocol as ≥ 1 of the following: initiation of chronic opiates, ECOG performance status (PS) decline to ≥ 3, or initiation of chemotherapy, palliative radiation therapy, or surgery. OS was evaluated for each type of progression using Cox proportional hazard models. Results: 500 (92%) pts in the AA arm and 540 (100%) in the P arm discontinued study treatment. Of the 736 pts who discontinued treatment for a protocol-defined reason, 280 (38%) discontinued for UCP only, 332 (45%) for RAD only, and 124 (17%) for both UCP and RAD. Clinical events cited as the reason for discontinuation for UCP (AA vs P arm) included pain requiring opiates (22% vs 25%), ECOG PS ≥ 3 (4% vs 5%), and initiation of chemotherapy (50% vs 53%), radiation therapy (36% vs 27%) and surgery (3% vs 5%). UCP only pts had shorter median OS compared with RAD only pts (Table). Conclusions: UCP is a criterion used as an indicator for a censored event, yet appears to confer inferior survival relative to RAD. The high frequency of UCP implies that it may be an important determinant of clinical outcome. The events that drive UCP should be defined as part of the development of more informative interim trial end points, in line with the PCWG3-proposed “no longer clinically benefitting” outcome measure, which captures pts with UCP. Clinical trial information: NCT00887198. [Table: see text]

The National Radium-223 Dichloride Audit group: Data from patients in UK oncology centers with metastatic castration-resistant prostate cancer treated with radium-223 dichloride.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Manreet Randhawa ◽  
Robert J Jones ◽  
Irene Stratton ◽  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Univariate Analysis ◽  
Routine Care ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Laboratory Parameters ◽  
Castration Resistant ◽  
Radium 223 ◽  
The Uk

e16524 Background: Clinicians in 17 UK oncology centres comprise the National Radium-223 Dichloride Audit (NRDA) group which is evaluating treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride (Xofigo). Methods: Patients commencing treatment from 1st September 2017 were included. Clinical and laboratory parameters were collected throughout treatment. Analyses used frequency tables and univariate analysis. Results: As of February 2019, data from 400 patients has been collected. We report the outcomes on the first 150 patients who are evaluable. At first treatment, median age was 72 years (25th to 75th centile: 67-78), 54% of patients had an ECOG performance status (PS) of 1, 32.6% of patients had a WHO pain score of 1, 60% of patients had an ALP level of < 220U/L and 26% of patients received docetaxel for mCRPC. The mean number of cycles completed was 5. Sixty patients (40%) did not complete 6 cycles and 42/60 (70%) discontinued due to disease progression. Changes in variables between treatment 1 and 6 are shown in Table. Adverse events reported were fatigue (76%), diarrhoea (38%), nausea/vomiting (35%), constipation (32%), anaemia (28%), thrombocytopaenia (12%) and neutropaenia (5%). There was no overall change in ECOG PS. In those who completed quality of life (QOL) questionnaires at treatment 1 and 6 (58%), there was no difference. Conclusions: The ongoing NRDA Group records data from mCRPC patients treated across the UK in routine care. To our knowledge, it is the first prospective analysis of such patients and the largest in assessing treatment patterns and outcomes including QOL data as well as standard laboratory parameters. Disclosures: The NRDA Group has been funded by a research grant from Bayer.[Table: see text]

Impact of ECOG performance status on recurrent/metastatic head and neck squamous cell carcinomas treated with anti-PD1 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18004-e18004
Author(s):  
Cameron Chalker ◽  
Vicky Wu ◽  
Jenna M. Voutsinas ◽  
Victoria Hwang ◽  
Christina S Baik ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Smoking Status ◽  
Demographic Data ◽  
Performance Status ◽  
Univariate Analysis ◽  
Single Agent ◽  
Ecog Performance Status ◽  
Hpv Status

e18004 Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard of care for patients with recurrent/metastatic head & neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥ 2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received at least 1 dose of ICI at our institution. Demographic data and clinical outcomes were obtained; the latter included objective response to ICI (ORR), physician-documented CTCAE grade 2+ toxicity (irAE), and any unplanned hospitalization within 100-days of last ICI dose (UH). Associations between demographic data and clinical outcomes were explored using both uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, irAE, and UH were evaluated with logistic regression. This project was approved by our institutional IRB. Results: We identified 152 RMHNSCC patients who were treated with ICI between 1/2013 and 1/2019. ECOG PS was 0 in 42 (27%), 1 in 75 (50%), 2 in 27 (18%), 3 in 2 (1%), and unknown in 6 (4%) patients. The median age was 61 (range: 25 - 90). 124 (82%) were male, 124 (82%) were white, and 69 (45%) were never-smokers. The most common primary sites were the oropharynx (n = 59, 40%), oral cavity (n = 39, 26%), nasopharynx (n = 11, 7%), and larynx (n = 10, 6%). 54 (36%) were p16+ oropharynx cancers. CPS score was available in 10 (6.6%). Single agent ICI was received by 118 (77%) patients. 66 (44%) had a documented irAE and 54 (36%) had an UH. A multivariate model for OS containing PS, smoking status and HPV status showed a strong association between inferior OS and ECOG 2/3 compared to 0/1 (p < 0.001; HR = 3.30, CI = 2.01-5.41), as well as former (vs. never) smoking status (p < 0.001; HR = 2.17, CI = 1.41-3.35). Current smoking (p = 0.25) did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between irAE and any patient characteristic. Conclusions: We observed inferior overall survival among ICI-treated RMHNSCC patients with ECOG 2/3 in our single-institution, retrospective series. Our findings help frame discussion of therapeutic options in this poor-risk population. Further study must be done to determine which interventions are of greatest benefit for RMHNSCC patients with declining performance status.

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4439-4439 ◽  
Author(s):  
Osnat Bairey ◽  
Lev Shvidel ◽  
Chava Perry ◽  
Eldad J Dann ◽  
Rosa Ruchlemer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Event Free Survival ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Mean ◽  
Ecog Ps

Abstract Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin's lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown. Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded. Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%). Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056). Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. Fig 1: (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Fig 1:. (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Randomized study of docetaxel (D) and dexamethasone (DX) with low or high dose estramustine (E) for patients with advanced hormone-refractory prostate cancer (HRPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4653-4653
Author(s):  
T. Nelius ◽  
T. Klatte ◽  
F. Reiher ◽  
S. Filleur ◽  
R. Yap ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Bone Pain ◽  
Performance Status ◽  
Univariate Analysis ◽  
Total Daily Dose ◽  
High Dose ◽  
Ecog Performance Status ◽  
Significant Difference ◽  
Psa Response

4653 Background: D-based chemotherapy is a burgeoning option for men with advanced HRPC. Alone or in combination with E, D has been shown to improve median survival. In this study we tested the combination of D with two different doses of E in patients (pts) with HRPC to improve response rates and to lower side effects. Methods: 72 metastatic HRPC pts were randomly assigned to receive D (70 mg/m2 IV, d2, q3w) and E (3 × 280 mg/d PO starting 1 day prior to D, for 5 consecutive days) for arm A or E (3 x 140 mg/d PO starting 1 day prior to D, for 3 consecutive days) for arm B. Premedication with oral DX at a total daily dose of 16 mg, in divided doses two times a day was administered in arm A on day 1 to 5 and in arm B on day 1 to 3. Initially, 6 cycles were administered and repeated after significant PSA rise. Pts were monitored for PSA response, time to progression (TTP), survival and toxicity. Results: PSA declines of ≥75%, ≥50% and ≤50% were 36.8%, 55.3% and 44.7% in arm A and 38.2%, 67.6% and 32.4% in arm B, respectively (P = .442). TTP in Arm A and Arm B were 11 months (95% CI, 7–14) versus 14 months (95% CI, 8–19), P = .6911) and overall survival 21 months (95% CI, 6–35) versus 22 months (95% CI, 18–27), respectively, (P = .4149). The primary treatment-related side effects observed in arm A and arm B were granulocytopenia (34% and 29%, P = .663) and thrombotic complications caused by E (four pts (11%) and one pt (3%), respectively, P = .206). Associated baseline factors with overall survival in univariate analysis were ECOG performance status (P < .001), hemoglobin level (P < .001), bone pain (P < .001), and PSA (P < .097) and in multivariate analysis ECOG performance status (95% CI, 2.9–13.9) and bone pain (95% CI, 3.2–20.1), (P < .001). Conclusions: In this randomized phase II study the combination of D and E had substantial activity in HRPC. We did not find a statistically significant difference of higher dose of E in combination with D compared to a lower dose of E and D regarding PSA response, TTP and survival. However, there was a tendency of higher toxicity in the high dose E group. These treatment-related toxicities were mainly hematologic and manageable. The results of this study support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. No significant financial relationships to disclose.

The addition of prednisone (Pr) to the combination of docetaxel (T) and perifosine (P) decreases the severity of gastrointestinal (GI) toxicity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13142-13142
Author(s):  
B. Bernhardt ◽  
J. J. Nemunaitis ◽  
B. Ebrahimi ◽  
A. Cervera ◽  
R. Birch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Stable Disease ◽  
Phase 1 ◽  
Performance Status ◽  
Phase 1 Study ◽  
Ecog Performance Status ◽  
Prior Chemotherapy ◽  
Anticancer Treatment ◽  
Gi Toxicity

13142 Background: Miltefosine (M) is an alkophosholipid with activity as a topical treatment for cutaneous breast cancer lesions. Severe GI toxicity limited its development as a systemic anticancer treatment. P is an equipotent derivative of M with less GI toxicity, but nausea,(N), vomiting (V) & diarrhea (D) are still dose limiting. Methods: This phase 1 study evaluated whether the addition of Pr would enhance the tolerability of P & T in combination. Twenty-five patients (pts) were enrolled. The dose of T was 75 mg/m2 on day 8 of a 21 day cycle and half of the pts were randomized to also receive Pr, 5 mg bid. 50 mg of P was given orally 1, 2 or 3 times a day in successive cohorts on days 1 - 14 of each cycle. Results: Disease sites included lung 9, prostate 7, pancreas 3, ovary 2, breast 1 and other 4. The median age was 63 (range 41 - 80). 18 pts were male & median ECOG performance status was 1 (range 0–2). 22 pts had received a median of 2 prior chemotherapy regimens, 15 a prior taxane and 16 prior radiotherapy. Forty-two cycles of T+P were given without Pr (median 3 & range 1 - 18 per pt) and 84 cycles were given with Pr (median 4.5 cycles & range 1 - 17 per pt). The percentage of pts experiencing various grades (Gr) of N, V & D without and with prednisone are shown in the table below: Five of 12 pts not receiving Pr had gr 2 or 3 toxicities compared to 1 of 13 given Pr. (p<0.05) There were 7 pts evaluable for response not receiving Pr of whom 2 patients with prostate cancer had stable disease for 4+ and 10+ months. There were 9 evaluable pts receiving Pr; 3 partial responses (1 lung & 2, prostate pts) were seen and 1 prostate cancer was stable for 10 months. Patients given prednisone increased their average time on treatment by 50%, and this might be the reason that more responses were seen in this group. Conclusions: These data show that Pr decreases the severity of GI toxicity seen with T & P together and provide a rationale for further studies evaluating the effects of Pr on the toxicities of P either alone or in combination with other drugs. [Table: see text] [Table: see text]

Results from a phase I study of enzalutamide in combination with docetaxel in men with prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5066-5066
Author(s):  
Mark T. Fleming ◽  
Dana E. Rathkopf ◽  
Jackie Gibbons ◽  
Amy C. Peterson ◽  
Alison Hannah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Phase I ◽  
Phase I Study ◽  
Performance Status ◽  
Safety Data ◽  
Primary Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Combination Methods

5066 Background: Enzalutamide (ENZA) is a novel androgen receptor (AR) inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (DOC). DOC also prolongs survival in mCRPC and also appears to have anti-tumor effects mediated through the androgen-receptor axis, providing a compelling rationale for combining the two agents. CYP3A4 plays a role in DOC clearance and is induced by ENZA. We therefore conducted a phase I study to explore the PK and safety profiles of this combination. Methods: This study (NCT01565928) evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: Twenty-two pts were enrolled, 4 did not receive 2 full doses of DOC. As of 21 Sept 2012, preliminary PK and C1 and C2 safety data were available from 15 pts. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000/mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone.Final PK and updated tolerability and efficacy data beyond Cycle 2 will be presented. Conclusions: In mCRPC pts, ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.

Enzalutamide in combination with docetaxel in men with prostate cancer (PC): Preliminary results from a phase I study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 63-63 ◽  
Author(s):  
Mark T. Fleming ◽  
Dana E. Rathkopf ◽  
Jackie Gibbons ◽  
Amy C. Peterson ◽  
Alison Hannah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Translocation ◽  
Performance Status ◽  
Safety Data ◽  
Phase Iii ◽  
Primary Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Current Standard ◽  
Ecog Performance Status ◽  
To Receive

63 Background: Enzalutamide (ENZA), a novel oral androgen receptor (AR) inhibitor, inhibits AR signaling via inhibition of androgen binding to the AR, AR nuclear translocation, and nuclear AR-DNA binding. ENZA demonstrated a survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (Scher et al, NEJM 2012; 367:1187). A Phase III study in men with progressive chemotherapy-naïve disease (PREVAIL), is ongoing. Docetaxel (DOC) is the current standard first-line chemotherapy for mCRPC. CYP3A4, which plays a role in DOC clearance, is induced by ENZA. Patients (pts) eligible to receive DOC may benefit from continued AR inhibition with ENZA, provided the combination is well tolerated with no unacceptable drug-drug interactions. Methods: This study evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks, with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: As of 21 Sept. 2012, 22 pts have been enrolled, 3 did not complete both C1 and C2; PK and C1 and C2 safety data are currently available from 15 pts reported here. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone. Conclusions: This is the first evaluation of ENZA given in combination with DOC.In mCRPC pts ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.

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