Study Of Docetaxel Research Articles

A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non–Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade

BackgroundThere is an urgent and unmet need for more effective treatment options for patients with metastatic and recurrent non–small-cell lung cancer (NSCLC) who progressed on platinum-based therapy, immune checkpoint inhibitors (ICI), and targeted therapies. Currently, the combination of docetaxel (D) and ramucirumab (R) is the next best salvage therapy with a modest historical progression free survival (PFS) of 4.5 months and 6-month PFS rate of 37% predating the era of ICI use. Anecdotal reports in patients who progressed on ICI suggest a higher response rate to docetaxel compared to historical experience. Furthermore, tumor related angiogenesis promotes tumor growth and may contribute to immune escape in patients treated with ICI. Therapeutic combination with anti-angiogenic, ICI, and chemotherapy have independently demonstrated clinical efficacy without additive toxicities in NSCLC patients. Patients and methodsThis multicenter, single arm, open label, phase 2 study will evaluate the safety and preliminary efficacy of the combination of docetaxel 75 mg/m2, ramucirumab 10 mg/kg, and pembrolizumab 200 mg in up to 41 patients with metastatic or recurrent NSCLC after progression on concomitant or sequential platinum-based chemotherapy and ICI. This treatment will be given intravenously on the same day every 3 weeks until disease progression, occurrence of severe side effects, or no clinical benefit. The primary endpoint is 6-month PFS rate. ConclusionsThis is the first study to evaluate the safety and efficacy of ICI combined with docetaxel and ramucirumab. The findings could provide valuable information for developing new treatment strategies for NSCLC patients.

A pilot study of docetaxel and carboplatin for treatment of patients with mCRPC containing biallelic inactivation of genes in the BRCA1/2 pathway.

127 Background: Despite new treatments, metastatic castration resistant prostate cancer (mCRPC) remains ultimately lethal. Upwards of 25% of mCRPC tumors have alterations in homologous recombination DNA repair (HRD) genes, most frequently BRCA2. Retrospective data suggest addition of the DNA damaging agent carboplatin to standard docetaxel for patients with mCRPC whose tumors have biallelic inactivation of BRCA2 may be effective. Methods: In this prospective, pilot single-arm phase 2 study, we assess response to the combination of docetaxel 60mg/m2 and carboplatin AUC 5 IV q21 days in patients with mCRPC whose tumors have evidence of biallelic inactivation of BRCA1, BRCA2 or ATM and have progressed after any prior treatment, including prior docetaxel and/or PARP inhibitor (PARPi). The primary endpoint is rate of ≥50% PSA decline from baseline (PSA50). With H0 of PSA50 of 26%, 14 patients will provide 80% power to conclude H1 of PSA50 of 60% based on Simon's 2-stage design with 1-sided α = 5%. Secondary endpoints include PSA30, response duration, time to progression and correlative studies. Biallelic inactivation of other HRD-related genes were included at investigators’ discretion. Results: The study opened in Jan 2016 and has enrolled 8/14 (57%) of patients plus 5 patients with other HRD-related genes. 6/13 (46%) treated pts had grade 3 expected AEs, and no grade 4-5 AEs were observed. To date, 7/8 (88%) of pts with biallelic inactivation of BRCA1, BRCA2 and ATM (Table) and 10/13 (77%) of all pts achieved a PSA50 (other HRD-related genes include CDK12, CHD1, MRE11A and PALB2). Updated results will be reported at final presentation. Conclusions: Addition of carboplatin to docetaxel appears to be well-tolerated and effective for patients with mCRPC whose tumors have biallelic inactivation in selected HRD genes such as BRCA2, including those with prior treatment with PARP inhibitor. Clinical trial information: NCT02598895. [Table: see text]

A retrospective study of docetaxel combined with ADT therapy in the treatment of metastatic hormone-sensitive prostate cancer

Objective To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population. Methods A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital. 459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel. The mean age was (72.1±8.7)years. The median PSA level was 100.0 ng/ml, ranging 42.3-999.0 ng/ml. Patients of clinical T2, T3, T4 stage were 213(42.9%), 160(32.2%), 124(24.9%), respectively. Patients of clinical N0, N1, Nx stage were 319(64.2%), 144(29.0%), 34(6.8%), respectively. Patients of clinical M0, M1a, M1b, M1c, Mx stage were 100(20.1%), 51(10.3%), 332(66.8%), 9(1.8%), 5(1.0%), respectively. Gleason scores of biopsy showed that 146(29.4%) patients was ≤7, 103(20.7%) was 8 and 248(49.9%)was ≥9. Propensity score matching was used to match the baseline between groups. Caliper value was set at 0.02. SPSS 22 software was used to achieve a 1∶1 match between the two groups. There were no statistical difference in the age(P=0.102), PSA(P=0.713), T stage(P=0.113), N stage(P=0.226), M stage(P=0.514), Gleason score(P=0.612), tumor loading(P=0.812)between the two groups. The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test. Furthermore, forest plots were used to display the analysis results of different subgroups such as age, PSA, clinical stage, Gleason score, tumor load, whether patients had received palliative resection, and the differences in castration resistance-free rate were compared between the subgroups with high tumor load. Results The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group. The number of patients with castration resistance in the two groups was 23 and 17, respectively. There were 3 and 6 deaths, respectively. There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs. 16.5 m, P>0.05), and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m, P>0.05). When subgroup analysis was performed, it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs. 7.2 m, P=0.044), but there was no significant difference in the low- metastasis-volume subgroup(10.5 m vs.12.6 m, P>0.05). Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume, but not in low metastasis volume group. Key words: Prostatic neoplasms; Prostate cancer; Docetaxel; Chemotherapy; Androgen deprivation therapy; Propensity score matching

Phase I/II Study of Docetaxel and S-1 in Previously-Treated Patients with Advanced Non-Small Cell Lung Cancer: LOGIK0408.

Background: As docetaxel plus S-1 may be feasible for cancer treatment, we conducted a phase I/II trial to determine the recommended docetaxel dose and the fixed S-1 dose (phase I), as well as confirm the regimen’s efficacy and safety (phase II) for previously-treated patients with advanced non-small cell lung cancer. Methods: Patients ≤75 years with performance status ≤1 and adequate organ function were treated at three-week intervals with docetaxel on day 1 and 80 mg/m2 oral S-1 from days 1–14. The starting docetaxel dose was 45 mg/m2 and this was escalated to a maximum of 70 mg/m2. In phase II, response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. Results: The recommended doses were 50 mg/m2 docetaxel (day 1) and 80 mg/m2 S-1 (days 1–14). Grades 3 and 4 leukocytopenia and neutropenia occurred in 44% and 67% of patients, respectively. Nonhematologic toxicities were generally mild. Overall response to chemotherapy was 7.7% (95% confidence interval (CI), 1.6–20.9%), and median PFS and OS were 18.0 weeks (95% CI; 11.3–22.9 weeks) and 53.0 weeks, respectively. Conclusion: Fifty mg/m2 docetaxel plus 80 mg/m2 oral S-1 had a lower response rate than anticipated; however, the survival data were encouraging. A further investigation is warranted to select the optimal patient population.

LB-1 - A Phase I study of docetaxel plus synthetic lycopene in metastatic, castration-resistant and chemotherapy-naïve prostate cancer patients

LB-1 - A Phase I study of docetaxel plus synthetic lycopene in metastatic, castration-resistant and chemotherapy-naïve prostate cancer patients

FIERCE-21: Phase 1b/2 study of docetaxel + b-701, a selective inhibitor of FGFR3, in relapsed or refractory (R/R) metastatic urothelial carcinoma (mUCC).

4534Background: Patients with locally advanced or metastatic urothelial carcinoma (mUCC) have a poor prognosis. FGFR3 is frequently overexpressed in UCC and 15-20% of patients with mUCC have FGFR3 ...

A subgroup analysis of the East Asia population in RANGE: A randomized phase 3 study of docetaxel (DOC) with or without ramucirumab (RAM) in platinum-refractory advanced or metastatic urothelial carcinoma (UC).

4542Background: RANGE (NCT02426125) is a global, randomized, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy and safety of RAM in combination with DOC in patients (pts) wit...

A Prospective Phase I/II Study of Docetaxel, Cisplatin and Continuous Capecitabine in Advanced Oesophago-Gastric Cancer (NWCOG-3)

AimsThis open-label prospective phase I/II dose-escalation study determined the maximum tolerated dose (MTD) and then evaluated response, safety and feasibility of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in chemotherapy-naive patients with advanced oesophago-gastric carcinoma. Materials and methodsPatients with adenocarcinoma or squamous cell carcinoma of the oesophagus or stomach, of good performance status, deemed too advanced for curative treatment, were given systematically increasing doses of 3 weekly DCC to ascertain the MTD. Phase II administered up to six cycles of DCC at the MTD, assessing response and toxicity. ResultsBetween November 2007 and November 2012, 15 patients were recruited into phase I and 41 into phase II. The MDT was a 21 day cycle of docetaxel 60 mg/m2 IV day 1, cisplatinum 60 mg/m2 IV day 1 and oral capecitabine 1000 mg/m2 daily in two divided doses for days 1–21. The most common phase II grade 3–4 toxicities were neutropenia 88% (10% febrile neutropenia), fatigue 15%, sensory neuropathy 10% and non-neutropenic infection 10%. The overall response rate was 51%, median progression-free survival was 7.4 months (confidence interval 6.7–9.4) and median overall survival was 10.9 months (confidence interval 7.7–13.7). ConclusionDCC was tolerable and feasible with promising efficacy, and may be suitable for future investigation in both first-line metastatic and neoadjuvant settings.

A dose-escalation study of docetaxel, oxaliplatin and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer.

174 Background: Although the triplet regimen of docetaxel/cisplatin/S-1 (DCS) has shown promising activity and conversion rate in patients with unresectable metastatic gastric cancer (UMGC) in Japan, it was accompanied by severe adverse events. Recent studies suggested that oxaliplatin was almost as active, and relatively less toxic, than cisplatin in combination regimens for UMGC and can therefore replace cisplatin. The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended dose (RD), and preliminary efficacy of docetaxel/oxaliplatin/S-1 (DOS) instead of DCS in patients with UMGC. Methods: Previously untreated 16 patients with histologically proven UMGC were enrolled. Docetaxel and oxaliplatin were administered intravenously on day 8. S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. DLTs were evaluated during the first cycle of treatment. Three dose-escalations of DOS were used in this study namely, level 1 (50/100/80 mg/m2), level 2 (50/130/80 mg/m2), and level 3 (60/130/80 mg/m2). Results: Among the six patients, one patient each experienced DLTs (febrile neutropenia and diarrhea) at level 1 and 2 doses, respectively. While two more patients experienced DLTs (febrile neutropenia and diarrhea) after administration of level 3 doses. Therefore, two additional patients were enrolled into the study at level 2. However, both these patients subsequently exhibited DLTs (febrile neutropenia and diarrhea). Therefore, we concluded that the MTD and RD with this regimen were level 2 and level 1, respectively, and that the DLT were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) of the patients with measurable lesions, consisting of two complete response and five partial responses. Five patients underwent conversion surgery. Conclusions: The RD of the 3-weekly DOS regimen in patients with UMGC was docetaxel at 50 mg/m2 and oxaliplatin at 100 mg/m2 on day 8 and S-1 at 80 mg/m2 on days 1-14. The efficacy and ease of administration make the regimen a promising alternative to DCS. A phase II study using this RD regimen is currently underway. Clinical trial information: 000015849.

Subgroup analysis of patients (Pts) refractory to first-line (1L) chemotherapy from REVEL, a randomized phase 3 study of docetaxel (DOC) with ramucirumab (RAM) or placebo (PBO) for second-line (2L) treatment of stage IV non-small-cell lung cancer (NSCLC)

Background: In the phase 3 REVEL trial, RAM+DOC for 2L treatment of advanced NSCLC significantly improved overall survival (OS), progression-free survival (PFS) and objective response rate (ORR), independent of histology. Pts refractory to 1L therapy have a poor prognosis and are challenging to treat; we report relevant outcomes in such pts, including those with adenocarcinoma, from REVEL. Material (patients) and methods: Refractory pts had progressive disease as best response to platinum-based treatment. Pts were randomized (1:1) to DOC 75mg/m2+ RAM 10mg/kg or PBO every 21 days. Assessments included: response [RECIST v1.1]; treatment-emergent adverse events (TEAEs) [NCI-CTCAE, version 4.0]; quality of life (QoL) [Lung Cancer Symptom Scale (LCSS)]. Results: Of 1253 REVEL pts, 29% were refractory (including 17% with refractory adenocarcinoma). Baseline characteristics of refractory pts were balanced between treatment arms (Table 1). RAM+DOC improved OS, PFS and ORR in refractory pts overall and the subgroup with adenocarcinoma (Table 2). No new safety concerns or increased detriment in QoL were identified in either group of refractory pts (Table 3).Tabled 1SubgroupOverallAdenocarcinomaRAM+DOCPBO+DOCRAM+DOCPBO+DOCn = 178n = 182n = 111n = 101Total LCSS score, time to deterioration HR (95%CI)0.77 (0.51,1.17)0.81 (0.47,1.41)TEAEs, n(%)Any173(97)171(95)108(97)101(100)Grade ≥3131(74)126(70)82(74)73(72)Serious80(45)84(47)47(42)48(48)Leading to discontinuation9(5)7(4)6(5)4(4)Leading to death11(6)17(9)4(4)11(11) Open table in a new tab Table 1: E3Baseline characteristics, n(%)RAM+DOCPBO+DOCn = 178n = 182Age, median (range), years63(23-84)60(29-87)Male137(77)127(70)ECOG PS053(30)50(27)1125(70)132(73)<9 months since prior therapy156(88)154(85)HistologyNonsquamous130(73)130(71)Adenocarcinoma111101Squamous46(26)50(27)ECOG PS, Eastern Cooperative Oncology Group performance status Open table in a new tab Table 2: E3SubgroupOverallAdenocarcinomaRAM+ DOCPBO+ DOCHR (95% CI)RAM+ DOCPBO+ DOCHR (95% CI)n = 178n = 182n = 112n = 101MedianOS, m8.36.30.86(0.68, 1.08)8.56.20.79(0.57, 1.09)MedianPFS, m4.02.50.71(0.57, 0.88)4.02.60.63(0.47, 0.85)ORR23%13%20%15%CI, confidence interval; HR, hazard ratio; m, months Open table in a new tab ECOG PS, Eastern Cooperative Oncology Group performance status CI, confidence interval; HR, hazard ratio; m, months Conclusions: The effect of RAM+DOC for treating pts with advanced NSCLC refractory to 1L therapy appears consistent with that for the intent-to-treat population. The benefit/risk profile for refractory pts, including pts with refractory adenocarcinoma, suggests that RAM+DOC is an appropriate treatment option even in this difficult-to-treat population.

LBA4_PR - RANGE: A randomized, double-blind, placebo-controlled phase 3 study of docetaxel (DOC) with or without ramucirumab (RAM) in platinum-refractory advanced or metastatic urothelial carcinoma

Background: Limited treatment options are available for patients (pts) with platinum-refractory advanced or metastatic urothelial carcinoma (UC). In a previous randomized phase 2 study (NCT01282463) of platinum-refractory metastatic UC, RAM plus DOC significantly improved median progression-free survival (PFS) over DOC (5.4 vs 2.8 months; HR, 0.389; 95% CI, 0.235-0.643; P = 0.0002) with no unexpected toxicities. To confirm these results, we conducted a randomized phase 3 trial in a similar pt population. Methods: In this randomized, double-blind, phase 3 trial, pts with progressive advanced or metastatic UC during or after platinum-based chemotherapy were enrolled. Additional prior treatment with 1 immune checkpoint inhibitor was permitted. Pts were randomized (1:1) to receive DOC 75 mg/m2 with RAM 10 mg/kg or placebo (PL) on day 1 of a 21-day cycle until disease progression or other discontinuation criteria. Primary endpoint was investigator-assessed PFS, analyzed in the first 437 randomized (intention-to-treat, ITT) pts. Secondary endpoints included overall survival (OS), objective response rate (ORR), safety, and quality of life as assessed with the EORTC QLQ-C30. Radiographic assessment occurred every 6 weeks. Results: 530 pts were randomized to RAM plus DOC (n = 263) or PL plus DOC (n = 267). PFS was significantly prolonged in pts treated with RAM plus DOC versus PL plus DOC (median, 4.1 vs 2.8 months; HR, 0.757; 95% CI, 0.607-0.943; p = 0.0118). A blinded central analysis demonstrated consistent PFS results (HR, 0.672; 95% CI, 0.536-0.842; p = 0.0005). ORR in the first 437 ITT population was 24.5% (95% CI, 18.8-30.3) in the RAM arm and 14.0% (95% CI, 9.4-18.6) in the PL arm. OS data are immature. Grade ≥3 adverse events (AEs) were reported at a similar frequency in both arms with no unexpected toxicities; neutropenia was the most common grade ≥3 AE (15% RAM arm vs 14% PL arm). Mean scores for global quality of life were relatively unchanged over time, with no differences between arms. Conclusions: RAM plus DOC is the first regimen in a phase 3 study to show superior PFS over chemotherapy in pts with platinum-refractory advanced UC. Clinical trial identification: NCT02426125 Legal entity responsible for the study: Eli Lilly and Company Funding: Eli Lilly and Company Disclosure: K.N. Chi: Clinical trial costs from Eli Lilly and Company, during the conduct of the study. C.N. Sternberg: Personal fees for participating in an advisory board and institutional research funding from Eli Lilly and Company, during the conduct of the study. R. de Wit: Grant support or personal fees from Lilly, Merck, Roche and Sanofi. E.Y. Yu: Honorarium and institutional research funding from Eli Lilly and Company A. Fléchon: Personal fees and non-financial support from Janssen, Novartis, Astellas, Sanofi, Roche, MSD, Pfizer, Ipsen, Bayer, Astra Zeneca, outside the submitted work; . M.S. van der Heijden: Personal fees from Roche/Genentech, AstraZeneca, Astellas, BMS, and grants from Astellas, outside the submitted work. N. Matsubara: Honoraria from MSD, AstraZeneca, Eisai, Ono, Kissei, Sanofi Taiho, Takeda, Chugai, Novartis, Bayer Yakuhin, Pfizer Japan, Merck Serono Co., Janssen; research funding from Shionogi, Bayer Yakuhin, Janssen, Chugai, Eli Lilly Japan, Eisai, MSD R.A. Walgren, O. Hamid, A.H. Zimmermann, K.M. Bell-Mcguinn: Employee and shareholder of Eli Lilly and Company T. Powles: Honoraria from Roche, Merck, AstraZeneca, BMS, Lilly, Pfizer; and research funding from Roche and AstraZeneca. All other authors have declared no conflicts of interest.

100P Phase III of study of docetaxel and carboplatin with or without doxorubicin hydrochloride and cyclophosphamide in treating women with triple negative breast cancer

100P Phase III of study of docetaxel and carboplatin with or without doxorubicin hydrochloride and cyclophosphamide in treating women with triple negative breast cancer

Final Survival Analysis of ROSE/TRIO-012.

TO THE EDITOR: No antiangiogenic strategy in breast cancer has yet demonstrated a clinically meaningful improvement in the ultimate end point of all-cause mortality despite improvements in progression-free survival and response rates in metastatic disease and improvements in pathologic complete response rates in the neoadjuvant setting. Why antiangiogenic studies have not produced long-term survival effects is unclear, triggering speculation that interrupting antiangiogenic treatment increases the aggressiveness of the disease, or that resistance mechanisms circumventing the vascular endothelial growth factor pathway evolve rapidly. The ROSE/TRIO-012 (Phase III Study of Docetaxel 1 Ramucirumab or Placebo in Breast Cancer) trial was a study in women with metastatic breast cancer receiving first-line docetaxel; the primary analysis showed no significant improvement in progressionfree survival with the addition of ramucirumab over placebo, and the interim survival analysis was immature. We now report the completed protocol-specified final analysis for overall survival. In the intention-to-treat population, there were 492 survival events in the ramucirumab group (492 of 759 [65%]) and 264 in the placebo group (264 of 385 [69%]). Median survival was 30.3 months (95% CI, 27.5 to 33.5 months) for the ramucirumab group and 28.7 months (95% CI, 25.6 to 32.3 months) for the placebo group, with the stratified hazard ratio of 0.95 (95% CI, 0.81 to 1.10) for overall survival showing no difference (stratified log-rank P 5 .49; Fig 1). We conclude that ramucirumab, like other antiangiogenic strategies used in the therapy of metastatic breast cancer does not influence all-cause mortality. Given that the goals of treatment of metastatic breast cancer are to improve duration and quality of life, there remains no indication for the addition of ramucirumab to docetaxel in the first-line therapy of metastatic breast cancer.

Circulating Tumor Cells in a Phase 3 Study of Docetaxel and Prednisone with or without Lenalidomide in Metastatic Castration-resistant Prostate Cancer

Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). Patient summaryOur study in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.

A phase II randomized study of docetaxel +/- low-dose, short course sunitinib in advanced solid tumours.

e14124Background: Low dose, short course anti-angiogenic agents may normalize tumor vasculature to improve drug delivery. We previously showed 12.5mg sunitinib (Su) for 7 days before neoadjuvant do...

Characteristics of Chinese patients with advanced prostate cancer: A muliticentre, non-interventional, observational, prospective, registry study of docetaxel.

328 Background: Prostate cancer (PC) is the second most frequently diagnosed malignancy in males worldwide, and stands in 7th place among malignancies in Chinese males. This study investigated the real-world treatment patterns of docetaxel as chemotherapy in patients with advanced PC in China. Methods: This was a multi-center, prospective, observational, non-interventional, product registry study. All patients with advanced PC who failed with previous endocrine therapies, were receiving docetaxel containing chemotherapy, and consented to participate in the study were eligible to be enrolled. Patients were followed-up 2 years, for the collection and analysis of data on docetaxel treatment mode, prostate specific antigen (PSA) remission rate, survival time, etc. Results: A total of 407 patients were enrolled from Aug 2011 through Jun 2014, with a mean Gleason score of 8.0 (SD: 1.11), and median PSA of 61.0 (range: 0.0 to 5000.0) ng/ml. 302 (74.2%) patients were classified as clinical stage IV. For Eastern Cooperative Oncology Group (ECOG) score, 145 (35.6%), 205 (50.4%), 48 (11.8%), patients had scores of 0, 1, 2, respectively. Metastasis to bone was present in 340 (83.5%) patients; metastasis to other organs (liver, lungs, adrenal glands, brain, etc.) was present in 57 (14.0%) patients. Last disease progression prior to enrolment was evidenced by tumor progression in 132 (32.4%) patients and by PSA elevation in 379 (93.1%) patients. 173 (43.0%) and 120 (29.9%) patients started docetaxel therapy after failure of the first line and second line endocrine therapies, respectively; 51 (12.7%) patients after failure of the third line or more endocrine therapies. Conclusions: This abstract presented characteristics of Chinese patients with advanced PC revealed by a Chinese PC study, which indicated Chinese patients were in later stage and higher risk compared with their western counterparts. The majority of patients started docetaxel therapy after failure of first line and second line endocrine therapies. PSA elevation and tumor progression were the 2 main causes that Urologists determined for disease progression. Clinical trial information: no registration number.

2300 A multicenter randomized phase II study of docetaxel vs. docetaxel plus cisplatin vs. docetaxel plus S-1 as second-line chemotherapy in metastatic gastric cancer patients who had progressed after cisplatin plus either S-1 or capecitabine

2300 A multicenter randomized phase II study of docetaxel vs. docetaxel plus cisplatin vs. docetaxel plus S-1 as second-line chemotherapy in metastatic gastric cancer patients who had progressed after cisplatin plus either S-1 or capecitabine

Phase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck

We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66Gy in 33 fractions. Docetaxel, 10mg/m(2), followed by cisplatin, 20mg/m(2), administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9months (range: 15.6-113.9months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2years postchemoradiation therapy in patients who survived without local treatment failure. Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.

Interim results of a randomized phase 2 study of docetaxel with ramucirumab versus docetaxel in second-line advanced or metastatic urothelial carcinoma.

295 Background: Patients (pts) with metastatic urothelial carcinoma (UC) progressing after first-line chemotherapy have limited treatment options. Ramucirumab (Ram), a human VEGFR2-targeted mAb, has demonstrated clinical activity in several solid tumors. Preclinical testing supports a role for Ram-taxane combinations in UC. Study JCDC is an open-label, multicenter, randomized phase 2 study of docetaxel (Doc) alone or combined with Ram or icrucumab (Icr) in locally advanced or metastatic platinum-resistant UC. We report on a planned interim analysis for Doc + Ram vs Doc; Icr results will be reported later. Methods: Eligible pts with advanced UC and ECOG PS 0-1 who relapsed ≤ 1 year from a platinum-regimen were randomized to receive Doc 75 mg/m2IV alone or with Ram 10mg/kg IV on Day 1 of repeating 21-day cycles. A sample size of 46 pts per arm enabled 71% power to demonstrate statistical significance of 4.5 mo (Doc + Ram) vs 3 mo (Doc) at a 1-sided α= 0.1. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed PFS with RECIST v1.1, analyzed by K-M methods. A planned interim analysis was performed after 75% of the PFS events. Results: 44 pts received Doc and 46 received Doc + Ram. Study arms were well matched with a mean age of 67 yr (29-84), and a 4:1 male to female ratio. 58.7% (Doc + Ram) vs 61.4% (Doc) had ECOG PS 1. 58.7% (Doc + Ram) vs 52.3% (Doc) had visceral metastases. Doc + Ram reduced the risk of disease progression, stratified HR = 0.388; 95% CI: 0.222, 0.677; log-rank p = 0.0005, improving median PFS (5.1 vs 2.4 mo). The ORR for Doc + Ram was 19.6 vs 4.5% for Doc (p= 0.0502), and the disease control rate was 67.4 vs 43.2%. OS maturity is pending. The most common adverse events in the Doc + Ram arm (all grades) were fatigue (80.4% Doc + Ram v 75.0% Doc), decreased appetite (54.3 v 43.2%), nausea (54.3 v 25.0%), and neuropathy (50.0 v 38.6%). Grade (G) ≥3 febrile neutropenia (19.6 v 11.4%), pneumonia (13 v 9.1%), hypertension (4.3 v 0%) were higher with Doc + Ram. One G3 hematuria was observed in each arm. Conclusions: Results support a statistically significant improvement in PFS for Doc + Ram in second-line UC. Final results are expected in 2015. Clinical trial information: NCT01282463.

A Phase 2 Study of Docetaxel in Combination with Indoximod for Metastatic Breast Cancer

ABSTRACT Background Indoleamine 2,3dioxygenase (IDO) is a tryptophan-catabolizing enzyme that plays a key role in the regulation of immune tolerance. Tumors also employ this mechanism to induce a state of immunosuppression, evading immune mediated destruction. Indoximod (D-1-methyltryptophan) is a broad IDO pathway inhibitor as it has been shown to potentially interfere with multiple targets within the IDO pathway. Preclinical studies in MMTV-neu mouse models have shown that indoximod combined with chemotherapy was more effective in causing tumor regressions than either agent alone. A phase 1 trial combining docetaxel and indoximod demonstrated safety and responses in metastatic breast cancer patients. Based on this data a phase 2 trial in first line metastatic breast cancer was initiated. Trial design The study is a 1:1 randomized, placebo controlled two arm phase 2 study. The study treatment is docetaxel 75mg/m2 IV D8 plus indoximod 1200mg PO BID D1-14 every 21 days or matching placebo. Primary endpoint is progression free survival. Secondary endpoints include overall survival, response rate, and immune response correlative assays. Patients with measurable, histologically confirmed metastatic breast cancer, no prior chemotherapies (hormonal therapies allowed) in the metastatic setting, ER+ or ER –, HER2 -, ECOG PS 0-1, no active CNS disease, no active autoimmune disease are eligible. Target enrollment is 154 patients. The trial is currently open at multiple clinical sites all around the US and actively enrolling patients. Expansion to the EU is underway. NCT01191216. Disclosure E.P. Kennedy: Employee of NewLink Genetics who is the sponsor for this clinical trial; G. Rossi: Author is an employee of NewLink Genetics; N. Vahanian and C. Link: Author is an officer and employee of NewLink Genetics. All other authors have declared no conflicts of interest.