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Background: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. Methods: Patients with cT3–4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). Results: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26–73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432–1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429–1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. Conclusions: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Chemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC. Patients and methods: The patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4–6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate. Results: From February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%. Conclusion: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile. Trial registration: ClinicalTrials.gov identifier: NCT03443661, 23/02/2018. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with nab-paclitaxel and S-1 followed by S-1 maintenance therapy.Methods: Nab-paclitaxel was administered intravenously on days 1 and 8 at 120 mg/m2. S-1 at 120 mg/day (for surface area ≥ 1.5 m2), 100 mg/day (for surface area between 1.25-1.5 m2), and 80 mg/day (for surface area < 1.25 m2) were given two times daily on days 1-14 every 3 weeks. Patients who achieved response and stable disease after 6 cycles were given S-1 maintenance treatment in the same schedule until disease progression or unacceptable toxicity developed. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Between 01/2015 and 07/2017, 32 patients were enrolled.Results: The ORR in the intention-to-treat (ITT) population (N = 32) was 53.1%, and the DCR was 87.5%. In the 30 evaluable patients, the ORR and DCR were 56.7 and 93.3%, respectively. The median follow-up time was 18 (range 12-36) months, the median PFS was 6.2 (range 4.4-8) months, and the median OS was 13.6 (range 8.7-18.5) months. The incidence of grade 3/4 neutropenia was 27.6%. Other grade 3 adverse events included 1 (3.1%) hand-foot syndrome, 1 (3.1%) rash and 2 (6.3%) diarrheas.Conclusions: Nab-paclitaxel and S-1 regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Principal stratification is a causal framework to analyse randomized experiments with a post-treatment variable between the treatment and end point variables. Because the principal strata defined by the potential outcomes of the post-treatment variable are not observable, we generally cannot identify the causal effects within principal strata. Motivated by a real data set of phase III adjuvant colon cancer clinical trials, we propose approaches to identifying and estimating the principal causal effects via multiple trials. For the identifiability, we remove the commonly used exclusion restriction assumption by stipulating that the principal causal effects are homogeneous across these trials. To remove another commonly used monotonicity assumption, we give a necessary condition for the local identifiability, which requires at least three trials. Applying our approaches to the data from adjuvant colon cancer clinical trials, we find that the commonly used monotonicity assumption is untenable, and disease-free survival with 3-year follow-up is a valid surrogate end point for overall survival with 5-year follow-up, which satisfies both causal necessity and causal sufficiency. We also propose a sensitivity analysis approach based on Bayesian hierarchical models to investigate the effect of the deviation from the homogeneity assumption. [ABSTRACT FROM AUTHOR]