Concurrent Docetaxel Research Articles

Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p=.96) or grade 2 gastrointestinal (p=.75), genitourinary (p=.44), and sexual (p=.29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p=.03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p=.005). A nonsignificant trend (p=.09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.

A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy.

e20569 Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.

Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial.

The interim analysis of the ENZAMET trial of testosterone suppression plus either enzalutamide or standard nonsteroidal antiandrogen therapy showed an early overall survival benefit with enzalutamide. Here, we report the planned primary overall survival analysis, with the aim of defining the benefit of enzalutamide treatment in different prognostic subgroups (synchronous and metachronous high-volume or low-volume disease) and in those who received concurrent docetaxel. ENZAMET is an international, open-label, randomised, phase 3 trial conducted at 83 sites (including clinics, hospitals, and university centres) in Australia, Canada, Ireland, New Zealand, the UK, and the USA. Eligible participants were males aged 18 years or older with metastatic, hormone-sensitive prostate adenocarcinoma evident on CT or bone scanning with 99mTc and an Eastern Cooperative Oncology Group performance status score of 0-2. Participants were randomly assigned (1:1), using a centralised web-based system and stratified by volume of disease, planned use of concurrent docetaxel and bone antiresorptive therapy, comorbidities, and study site, to receive testosterone suppression plus oral enzalutamide (160 mg once per day) or a weaker standard oral non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide; control group) until clinical disease progression or prohibitive toxicity. Testosterone suppression was allowed up to 12 weeks before randomisation and for up to 24 months as adjuvant therapy. Concurrent docetaxel (75 mg/m2 intravenously) was allowed for up to six cycles once every 3 weeks, at the discretion of participants and physicians. The primary endpoint was overall survival in the intention-to-treat population. This planned analysis was triggered by reaching 470 deaths. This study is registered with ClinicalTrials.gov, NCT02446405, ANZCTR, ACTRN12614000110684, and EudraCT, 2014-003190-42. Between March 31, 2014, and March 24, 2017, 1125 participants were randomly assigned to receive non-steroidal antiandrogen (n=562; control group) or enzalutamide (n=563). The median age was 69 years (IQR 63-74). This analysis was triggered on Jan 19, 2022, and an updated survival status identified a total of 476 (42%) deaths. After a median follow-up of 68 months (IQR 67-69), the median overall survival was not reached (hazard ratio 0·70 [95% CI 0·58-0·84]; p<0·0001), with 5-year overall survival of 57% (0·53-0·61) in the control group and 67% (0·63-0·70) in the enzalutamide group. Overall survival benefits with enzalutamide were consistent across predefined prognostic subgroups and planned use of concurrent docetaxel. The most common grade 3-4 adverse events were febrile neutropenia associated with docetaxel use (33 [6%] of 558 in the control group vs 37 [6%] of 563 in the enzalutamide group), fatigue (four [1%] vs 33 [6%]), and hypertension (31 [6%] vs 59 [10%]). The incidence of grade 1-3 memory impairment was 25 (4%) versus 75 (13%). No deaths were attributed to study treatment. The addition of enzalutamide to standard of care showed sustained improvement in overall survival for patients with metastatic hormone-sensitive prostate cancer and should be considered as a treatment option for eligible patients. Astellas Pharma.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Efficacy and Safety of Concurrent Chemoradiotherapy with Docetaxel for Locally Advanced Breast Carcinoma after Modified Radical Mastectomy

Background: Breast cancer is a common term for a malignant tumor that arises from the epithelial component of the breast. Concurrent chemoradiotherapy’s efficacy and safety are controversial, considering the impact on patients' quality of life. Objectives: The aim of this study was investigating the efficacy and safety of concurrent chemoradiotherapy with docetaxel in locally advanced breast cancer who have received a modified radical mastectomy. Methods: A cohort of 110 female patients with locally advanced breast cancer were included in the present study and divided by chemoradiotherapy mode into a concurrent chemoradiotherapy group (n=58) and a sequential chemoradiotherapy group (n=52). Docetaxel was administered concurrently during radiotherapy in the concurrent group, whereas the sequential group underwent adjuvant radiotherapy 1-3 weeks after chemotherapy. Then, the two groups were compared with respect to clinical efficacy, levels of tumor markers across vascular endothelial growth factor (VEGF) and Carcinoembryonic antigen (CEA), adverse reactions, and the 3-year overall survival (OS) rate. Results: The results showed that the mean age, operation, evaluation of Post treatment VEGF (pg / mg) and Post treatment CEA (/g / L), effectiveness of treatment in two sequential and concurrent treatment groups was not significant The results showed that the amount of Prior treatment VGEF (pg / mg) and Post treatment VGEF (pg / mg) in the two groups were statistically significant difference. Which shows the positive effect of this treatment before and after the intervention. Comparison of survival time in the two groups did not show a significant difference. Conclusion: The chemotherapy protocol with a combination of cyclophosphamide, fluorouracil and epirubicin with concurrent docetaxel presented higher efficacy and prolonged the overall survival in locally advanced breast cancer patients who had undergone a radical mastectomy, while it did not significantly increase the toxicity.

Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).

LBA5004 Background: The first planned interim analysis of ENZAMET, with 243 deaths after a median follow-up of 34 months, revealed a clinically meaningful overall survival benefit in mHSPC with the addition of enzalutamide to standard of care (hazard ratio 0.67, 95% CI 0.52 to 0.86, p=0.002, Davis et al, NEJM 2019). We now present updated overall survival (OS) findings from the prespecified analysis triggered to occur after 470 deaths. Methods: We randomly assigned participants (pts) with mHSPC to treatment with testosterone suppression (TS) plus either a conventional non-steroidal anti-androgen (NSAA) or enzalutamide. Stratification factors included age, volume of disease (high vs low according to the CHAARTED definition), and planned use of concurrent docetaxel assigned by the treating physician (docetaxel yes vs no). Results: We randomized 1125 pts with a median age of 69 years, including 503 in the docetaxel stratum, and 602 with high volume metastatic disease. OS results in the table below are based on 476 deaths, a median follow-up of 68 months, and a cut-off date of 19JAN2022. The hazard rate for death was 30% lower among all those assigned enzalutamide versus control (p&lt;0.0001). Outcomes by volume status are shown (Table) as well as the subgroups of interest with M1 high or low volume disease at diagnosis selected for concurrent docetaxel. Conclusions: Enzalutamide added to TS, compared with an active comparator of NSAA, provided clinically meaningful improvements in OS for the combined overall cohort, which persisted with an additional 3 years of follow-up. The benefits were more pronounced in pts with low volume disease, and were also seen in the subgroup with M1 high volume mHSPC despite the relatively high survival with TS+docetaxel+NSAA. ENZAMET was led by ANZUP Cancer Trials Group and the University of Sydney NHMRC Clinical Trials Centre, with funding support from Astellas. Clinical trial information: NCT02446405. [Table: see text]

Results of phase 3 randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer unsuitable for cisplatin-based chemoradiation.

LBA6003 Background: Systemic therapy options have not been systematically evaluated in cisplatin-ineligible locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients undergoing chemoradiation. This study evaluated docetaxel as a radiosensitizer in this setting. Methods: This was a randomised open-label study. Adults with LAHNSCC planned for radical or adjuvant chemoradiation, with ECOG PS 0-2 and who were cisplatin-ineligible as per the criteria by Ahn et al were enrolled. The patients were randomly assigned 1:1 to receive radiation alone or radiation with concurrent docetaxel 15 mg/m2 weekly for a maximum of 7 cycles. Adverse events were recorded in accordance with CTCAE version 4.03. The FACT-G, and H and N questionnaires (version 4) were self-administered at baseline, 6 months, 12 months and at 24 months. The primary endpoint was disease-free survival (DFS) and key secondary endpoints were overall survival (OS), adverse events and quality of life (Trial outcome index (TOI)). Results: The study recruited 356 patients with 176 in RT and 180 in the docetaxel-RT arm. The 2-year DFS was 30.3% (95%CI 23.6-37.4) versus 42% (95%CI 34.6-49.2) in the RT and docetaxel-RT arms respectively (Hazard ratio- 0.673; 95% CI 0.521-0.868; P-value=0.002). The median overall survival (OS) was 15.3 months (95%CI 13.1-22) in the RT arm and 25.5 months (95% CI 17.6-32.5) in the docetaxel-RT arm. (Log-rank P-value =.0.035). The 2 -year OS was 41.7% (95%CI 34.1-49.1) versus 50.8% (95%CI 43.1-58.1) in the RT and docetaxel-RT arms respectively (Hazard ratio-0.747; 95% CI 0.569-0.98; P-value=0.035). Any grade 3 or above adverse events were seen in 102 patients (58%) in RT and in 146 (81.6%) in docetaxel-RT arms respectively (P-value=0.000). There was a higher incidence of grade 3 and above mucositis (22.2% versus 49.7%; P&lt;0.001), odynophagia (33.5% versus 52.5%; P&lt;0.001) and dysphagia (33% versus 49.7%; P&lt;0.002) with the addition of docetaxel. The addition of docetaxel did not lead to a worsening of TOI scores and FACT-G scores at 6 months. Conclusions: The addition of docetaxel to radiation improved disease-free survival and overall survival in cisplatin-ineligible LAHNSCC and represents a new standard of care. Clinical trial information: CTRI/2017/05/008700.

Long-term toxicity and tolerance of concurrent docetaxel with radiotherapy in cisplatin ineligible head and neck cancer patients.

e18037 Background: Docetaxel can be administered in several situations like low creatinine clearance or pre-existing grade 3-4 ototoxicity, where cisplatin is contraindicated. In this analysis, we present our data on toxicity and tolerance to docetaxel-based chemoradiation in cisplatin-ineligible patients. Methods: Patients who underwent docetaxel-based chemoradiation between January 2015 to December 2017 for locally advanced head and neck cancer, either in the radical or adjuvant setting were selected for this analysis. SPSS version 16 was used for analysis. Results: Nineteen patients were identified and the median age of the cohort was 58 years (range 41-71 years). The most common site of the primary was the oral cavity (n = 9, 47.4%). Sixteen patients (84.2%) had stage IV disease and 3 patients (15.8%) had stage 3 disease. The intent of chemoradiation was radical in 12 (63.9%) patients and adjuvant in 7 (36.1%) patients. Any grade 3 or above adverse events were seen in 12 patients (63.2%). The most common grade 3 or above adverse events observed were mucositis and hyponatremia in 9 patients (47.4%) each. At a median follow up of 5.3 years, the 2-year and 5-year PFS were 26.3% (Standard error-10.1) and 15.8% (Standard error- 8.4) while 2-year and 5-year OS were 36.8% (Standard error-11.1) and 15.8% (Standard error- 8.4). Conclusions: Docetaxel based chemoradiation is a feasible and tolerated option in cisplatin unfit patients and needs further testing in large randomized studies to prove its worth.

Long-Term Outcomes of a Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image Guided Intensity Modulated Radiation Therapy for Localized High-Risk Prostate Adenocarcinoma

PurposeOur purpose was to describe the long-term outcomes seen with the addition of concurrent weekly docetaxel to high-dose intensity modulated radiation (IMRT) to the prostate and androgen deprivation therapy in patients with high-risk nonmetastatic adenocarcinoma of the prostate. Methods and MaterialsNineteen patients with high-risk, localized prostate cancer were treated in a phase I trial with concurrent docetaxel at doses of 10 to 30 mg/m2, in a dose-escalated scheme, in addition to IMRT (77.4 Gy/43 fx) and neoadjuvant and concurrent combined androgen blockade (gonadotropin-releasing hormone agonist and antiandrogen). A gonadotropin-releasing hormone agonist was continued for an additional 24 months post radiation. Kaplan-Meier analysis was used to estimate the survival probabilities. ResultsAt a median follow-up of 10.5 years, 5-year and 10-year overall survival were found to be 89.5% and 68.4%, respectively. The median metastasis-free survival and progression-free survival were determined to be 11.3 years and 9.0 years, respectively. ConclusionsThis regimen produced a 10-year overall survival of 68% with a 10-year metastasis-free survival of 58%. Grade >2 toxicity was minimal. These limited data suggest that the addition of concurrent weekly docetaxel to high-dose IMRT for high-risk prostate cancer warrants further investigation.

Neoadjuvant Therapy with Concurrent Docetaxel, Epirubicin, and Cyclophosphamide (TEC) in High-Risk HER2-Negative Breast Cancers.

Concurrent anthracycline and taxane is an effective and efficient way to deliver neoadjuvant chemotherapy for HER2-negative breast cancers. Data on efficacy and tolerance to 6cycles of concurrentdocetaxel, epirubicin, and cyclophosphamide (TEC)is limited. All patients with HER2-negative breast cancers who received neoadjuvant TEC from January 2013 to December 2019 were reviewed. A total of 71 patients [57 luminalB disease; 14 triple negative breast cancer (TNBC)] received neoadjuvant TEC with prophylactic granulocyte colony-stimulating factor (G-CSF). The pathological complete response (pCR) rate was 26.3% and 28.6% for luminalB and TNBC, respectively. With median follow-up of 48.9months, 3years disease-free survival was 85.9%, and 3years overall survival was 89.6%. Non-hematological toxicities were common but the majority was grade1 or 2. The most common grade3 or 4 toxicity were hematological, including neutropenia (26.8%) and anemia (15.5%). There was no cardiotoxicity observed. Half of the patients had at least one dose reduction but all patients completed the planned 6cycles and had breast surgery done. Six cycles of TEC with prophylactic G-CSF is an effective and tolerable neoadjuvant regime for HER2-negative breast cancers. Hematological toxicities were the most common toxicities. Although many patients required dose reduction, all patients completed treatment and there was no observed cardiotoxicity.

Docetaxel and nedaplatin twice a week with concurrent definitive radiotherapy in inoperable esophageal squamous cell carcinoma: A phase I trial (GASTO-1021)

PurposeThis phase I trial aimed to determine the maximal tolerated dose (MTD) of incorporating a twice-weekly docetaxel and nedaplatin regimen into definitive concurrent chemoradiotherapy (CCRT) as radiosensitizers in patients with inoperable esophageal squamous cell carcinoma (ESCC). MethodsThe CCRT regimen included docetaxel (5 mg/m2, 10 mg/m2, or 15 mg/m2) and nedaplatin (5 mg/m2, 10 mg/m2, or 15 mg/m2) twice-weekly based on the traditional 3 + 3 dose escalation strategy, and radiotherapy (64 Gy in 32 fractions). The primary goals were to determine the MTD of concurrent chemotherapy and the dose limiting toxicities (DLTs). In-field objective response rate (ORR) was investigated. ResultsFifteen patients had been recruited and analyzed. DLT involving persistent grade 3 esophagitis over 1 week was observed in all three patients (3/3) at dose level 3 (15 mg/m2), and two patients (2/6) experienced DLTs in the dose level 2 (10 mg/m2) due to esophageal fistula and persistent grade 3 esophagitis over 1 week, while one patient (1/6) treated at dose level 1 (5 mg/m2) exhibited DLT owing to Grade 3 increased liver enzymes, suggesting a MTD of 5 mg/m2. The in-filed ORR was both 100% in all patients and those receiving MTD. The 1-year loco-regional recurrence-free survival rate was 83.3%, 83.3% and 66.7% in dose level 1, 2, and 3, respectively. ConclusionsThe MTD of twice-weekly docetaxel and nedaplatin regimen was 5 mg/m2 in inoperable ESCC patients treated with definitive CCRT. Low dose concurrent docetaxel and nedaplatin showed promising radiosensitizing effect on in-filed disease control and good tolerability.

Abstract B04: Using PSA dynamics to forecast individual responses to intermittent androgen deprivation

Abstract Intermittent androgen-deprivation therapy (IADT) is an attractive treatment approach for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off has been shown to limit toxicities and reduce cumulative dose. While IADT has been shown to delay the development of treatment resistance, underlying mechanisms and actionable biomarkers are required to accurately predict when resistance will emerge and how to maximally delay time to progression. We developed a quantitative framework to simulate the enrichment of prostate cancer stem cell dynamics during treatment as a plausible mechanism of resistance evolution. Using simulated dynamics of cancer stem cells and nonstem cancer cells, we derive longitudinal blood serum prostate-specific antigen (PSA) concentrations that were calibrated to and validated with data of 70 patients undergoing multiple cycles of IADT. Model analysis suggests that cancer stem cell proliferation patterns correlate with PSA dynamics and patient outcomes. Learning these dynamics adaptively from the earlier treatment cycles in individual patients can predict the evolution of resistance in subsequent IADT cycles with a predictive power of 90%, which warrants prospective evaluation in a clinical setting. The model is used to simulate and predict alternative treatment options. In particular, simulations show that response dynamics from the first IADT cycle can be used to identify patients who would benefit from concurrent docetaxel. Citation Format: Renee Brady, Heiko Enderling. Using PSA dynamics to forecast individual responses to intermittent androgen deprivation [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B04.

Concurrent docetaxel and S-1 compared with oxaliplatin and s-1 as first-line therapy for advanced gastric adenocarcinoma: A retrospective study.

e16540 Background: The aim of this study was to compare the efficacy and safety between docetaxel plus S-1 with oxaliplatin plus S-1 therapy as first-line treatment for advanced gastric adenocarcinoma. Methods: Patients, who had received docetaxel plus S-1 or oxaliplatin plus S-1 as first-line chemotherapy for advanced gastric adenocarcinoma, were retrospectively reviewed. Kaplan–Meier curve and log-rank test were used to analyze the survival. Prognostic factors were estimated by Cox regression. Adverse events (AEs) were evaluated using CTCAE 4.0. Results: One hundred and twenty-nine patients received concurrent docetaxel plus S-1, whereas 130 received oxaliplatin plus S-1. The median progression-free survival (PFS) and overall survival (OS) in docetaxel and oxaliplatin groups were 6.0 and 8.2 months ( P= 0.025), 14.7 and 15.7 months ( P= 0.697), respectively. Multivariate Cox regression suggested that chemotherapy regimen (docetaxel vs oxaliplatin; HR = 1.535, 95% CI:1.092-2.156, P = 0.014), Eastern Cooperative Oncology Group performance status (ECOG PS 3-4 vs 0-2; HR = 4.213, 95% CI: 2.246–7.903, P&lt; 0.001), Lauren type (Intestinal vs Diffuse, HR = 0.471, 95% CI: 0.307–0.725, P= 0.001, Mixed vs Diffuse, HR = 0.649, 95% CI: 0.442–0.953, P= 0.028), and number of metastases (HR = 2.097, 95% CI: 1.421–3.095, P&lt; 0.001) had significant effects on PFS. Multivariate Cox regression suggested that pathologic types (signet-ring cell carcinoma vs adenocarcinoma; HR = 1.688, 95% CI:1.152-2.472, P = 0.007), Lauren type (Intestinal vs Diffuse, HR = 0.637, 95% CI: 0.414–0.982, P= 0.041), number of metastases (HR = 1.7, 95% CI: 1.154–2.504, P= 0.007) had significant effects on OS.The most common grade 3-4 adverse events were leukopenia (3.1% vs 7.8%), neutropenia (7.7 vs 12.3%), anemia (13.2% vs 14.6%), thrombocytopenia (2.3% vs 10.8%), peripheral neuropathy(0.8% vs 7.8%)and Nausea/vomiting/ anorexia (1.6% vs 3.8%). Conclusions: Concurrent oxaliplatin plus S-1 therapy appears to be effective as first-line treatment in advanced gastric and has an acceptable safety profile. For patients in good physical condition, we prefer to recommend oxaliplatin combined with S-1 for treatment.

Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation

Intermittent androgen deprivation therapy (IADT) is an attractive treatment for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off can reduce cumulative dose and limit toxicities. We simulate prostate-specific antigen (PSA) dynamics, with enrichment of PCa stem-like cell (PCaSC) during treatment as a plausible mechanism of resistance evolution. Simulated PCaSC proliferation patterns correlate with longitudinal serum PSA measurements in 70 PCa patients. Learning dynamics from each treatment cycle in a leave-one-out study, model simulations predict patient-specific evolution of resistance with an overall accuracy of 89% (sensitivity = 73%, specificity = 91%). Previous studies have shown a benefit of concurrent therapies with ADT in both low- and high-volume metastatic hormone-sensitive PCa. Model simulations based on response dynamics from the first IADT cycle identify patients who would benefit from concurrent docetaxel, demonstrating the feasibility and potential value of adaptive clinical trials guided by patient-specific mathematical models of intratumoral evolutionary dynamics.

Clinical impact of baseline renal function on the safety of radiotherapy with concurrent docetaxel for esophageal cancer in elderly patients.

We aimed to compare the safety of radiotherapy with concurrent docetaxel (DOC-RT) for esophageal cancer (EC) in elderly patients who were divided into a creatinine clearance (Ccr) < 60mL/min (Ccr-L) group and a Ccr ≥ 60mL/min (Ccr-H) group. Eligible patients included those aged ≥ 76years who were diagnosed with esophageal squamous cell carcinoma. The patients received radiotherapy (60Gy in 30 fractions) and concurrent docetaxel (10mg/m2 weekly for six cycles), after which toxicity and treatment completion rates were retrospectively evaluated. The 73 elderly EC patients receiving DOC-RT were divided into two groups for evaluation: the Ccr-L group (49 patients) and the Ccr-H group (24 patients). The median survival time for patients in the Ccr-L and Ccr-H groups was 21 and 20months, respectively (p = 0.2). The incidence of grade 1 acute kidney injury was 8% vs. 8% (p = 1) in the Ccr-L and Ccr-H groups, respectively. No other hematological or nonhematological toxicities differed between patients in the two groups. No grade 4 or 5 toxicities were observed in the two groups. No significant difference was observed in the treatment completion rates (88% vs. 92%, p = 1) between patients in the Ccr-L and Ccr-H groups. Regardless of baseline renal function, DOC-RT is a safe regimen for elderly patients with EC.

Clinical Impact of Primary Prophylactic Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel-Doxorubicin-Cyclophosphamide Chemotherapy.

PurposeThe regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN). This comparative study examined the clinical impact of long-acting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer.MethodsWe analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups.ResultsThe incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival (p = 0.033).ConclusionsThe use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer

Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high. To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019. Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil. Toxic effects, local (in-field) control, and overall survival rates. All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost. These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study. ClinicalTrials.gov identifier: NCT01102088.

Appropriateness of Radiotherapy with Concurrent Docetaxel in Elderly Patients with Esophageal Cancer

Appropriateness of Radiotherapy with Concurrent Docetaxel in Elderly Patients with Esophageal Cancer

Long-Term Follow-up of a Prospective Study of Simultaneous Integrated Boost for Dose Escalation in Locally Advanced Esophageal Cancer

To report long-term outcomes (risk of late toxicities, local control, and survival) of a simultaneous integrated boost for dose escalation in locally advanced esophageal cancer. Patients with unresectable esophageal cancer received chemoradiation with an SIB of 63 Gy to the gross target volume (GTV) and 50.4 Gy to the planning target volume (PTV), all in 28 fractions, with 5 weeks of concurrent docetaxel and capecitabine or fluorouracil. The end points were maximum tolerated dose, local recurrence free survival (LRFS) and overall survival (OS). 46 patients received protocol therapy. The median age was 65.5 years (range 37–84). Most patients (76%) were men; 84% had T3 disease, 39% had N1 disease, 22% had N2 disease, 13% had M1 disease, and 48% had adenocarcinoma. None experienced CTCAE grade 4 or 5 toxicity. At a median follow-up time of 23 months (range 3.3–84.0), 15 (32.6%) had local failure (median time to local failure 5 months [range 1– 23]). The 1-, 2-, and 3-year local control rate and overall survival rate were 69.6%, 66.6%, 62.1% and 86.9%, 53.6%, and 38.1%, respectively. Predictors for better local control included: KPS score ≥80 (P< 0.001), clinical CR (P< 0.001) and pathological CR (P< 0.001). The histology type of adenocarcinoma (P=0.021) and clinical complete response (P<0.001) were associated with better local LRFS. Better local control and OS were associated with clinical complete response (local control, P<0.001; OS, P=0.012). A comparison with 97 similar patients who received 50.4Gy without an SIB showed that the SIB significantly improved LRFS (P= 0.042) and OS (P=0.001) in all patients and in the subgroup of adenocarcinoma (LRFS, P= 0.016; OS, P=0.002) and patients without surgery (LRFS, P= 0.009; OS, P=0.008). Simultaneous integrated boost for dose escalation is a safe treatment with improvement in local control and overall survival in locally advanced esophageal cancer. No additional late toxicities were seen. A large prospective trial is needed in future.

Safety of radiotherapy with concurrent docetaxel in older patients with esophageal cancer

ObjectivesConsidering that therapeutic strategies for older adult patients with esophageal cancer (EC) remain controversial, we aimed to assess the safety of radiotherapy with concurrent docetaxel (DOC-RT) among older adult patients with EC. Materials and MethodsEligible patients included those aged ≥76 years who were diagnosed with esophageal squamous cell carcinoma. Patients received radiotherapy (60 Gy in 30 fractions) and concurrent docetaxel (10 mg/m2 weekly for six cycles). Survival, toxicity, and treatment completion rates were retrospectively evaluated. ResultsAmong 84 older adult patients receiving radical radiotherapy or chemoradiotherapy, 73 receiving DOC-RT were studied. Median follow-up duration was 14 months (range, 2–101 months). The 1-, 3-, and 5-year overall survival rates were 63%, 33%, and 13%, respectively, with a median survival time of 21 months. Grade 3 acute toxicities included esophagitis (7%), esophageal fistula (3%), pneumonitis (1%), leukopenia (10%), and anemia (8%). Grade 3 late toxicities included esophageal stenosis (4%), pleural effusion (3%), pericardial effusion (1%), and pneumonitis (1%). Grade 4 and 5 toxicities were not observed. DOC-RT was discontinued due to deterioration in the general condition (6%), esophageal fistula (3%), pneumonia (1%), and pain (1%), resulting in a DOC-RT completion rate of 89% (65/73 patients). The non-completion group comprised a higher proportion of older adults (age ≥ 80 years) and undernourished [geriatric nutritional risk index (GNRI <92)] patients than the completion group. ConclusionDOC-RT can be a safe regimen for older adult patients with EC. Nonetheless, old age (≥80 years) and undernourishment (GNRI <92) should be considered prior to DOC-RT administration.