BackgroundThe aim of this study was to determine whether early tumor shrinkage (ETS) at 6 weeks after treatment correlates with progression-free survival (PFS) and overall survival (OS) in advanced biliary tract cancer (BTC) patients receiving gemcitabine plus oxaliplatin (GEMOX), with or without erlotinib.MethodsThis was a multicenter, open label, randomized, phase III trial of 103 BTC patients (ClinicalTrials.gov Identifier; NCT01149122, and Rigistration date; January, 7, 2010), comparing GEMOX with GEMOX plus erlotinib. Tumor shrinkage was expressed as a relative decrease compared to baseline and was dichotomized according to a previously reported cutoff value of 10 %.ResultsFifty-four patients (52.4 %) received GEMOX and 49 patients (47.6 %) received GEMOX plus erlotinib. The latter achieved a better overall response rate (RR) (40.8 % vs. 18.6 %, p = 0.02) and showed ETS more frequently (63.2 % vs. 40.7 %, p = 0.03). ETS was significantly correlated with the overall RR (correlation coefficient, 0.53; p < 0.01). The median PFS and OS did not differ according to erlotinib administration. However, the median PFS (7.3 vs. 2.1 months, p < 0.01) and OS (10.7 vs. 5.8 months, p < 0.01) were significantly longer amongst patients with ETS at 6 weeks after treatment, irrespective of erlotinib administration. In patients with wild-type KRAS who were treated with GEMOX plus erlotinib, ETS was a significant prognostic factor for PFS (p < 0.01).ConclusionsETS might predict PFS and OS in BTC patients treated with GEMOX with or without erlotinib. Additionally, ETS may be an indication for adding erlotinib to chemotherapy for BTC patients wild-type KRAS. These findings need to be prospectively validated.

BackgroundKRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.MethodsPatients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6 year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients’ outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis.ResultsKRAS mutations were identified in 37.8 % of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank p = 0.425 for TTR; log-rank p = 0.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (G > A vs. G > T vs. G > C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung.ConclusionsKRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.

BackgroundWe designed a single-arm, open-label phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy (#NCT02449538).MethodsEverolimus was administered orally at a daily dose of 10 mg continuously (28-day cycles). Treatment was continued until progression of the disease or intolerable toxicity was observed. Based on Simon’s two-stage optimal design, 10 patients were treated with everolimus during the first stage.ResultsThe median age of the patients was 55.5 years (range, 42–72), and the median Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 2 (range, 1–2). Most of the patients (50.0%) had gastric cancer (GC) as the site of their primary tumor followed by colorectal cancer (CRC), pancreatic cancer, and cholangiocarcinoma. Patients received everolimus as a third-line (3 patients), fourth-line (4 patients), fifth-line (1 patient) or sixth-line (2 patients) treatment. Complete or partial responses were not observed in any of the patients. Four patients showed stable disease, resulting in a disease control rate of 40%. The median PFS was 1.6 months (95% CI, 0.8–2.4 months). Grade 3 or greater hematologic/non-hematologic toxicity was not observed. Grade 2 diarrhea and stomatitis were reported in one patient each. There were no treatment-related deaths. There was less than one response out of the 10 initial patients during the first stage, and the study did not progress to the second stage.ConclusionsThe study did not meet its primary objective of demonstrating the anti-tumor activity of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy. Further investigation using other genomic candidates and new-generation mTOR inhibitors is warranted in patients with treatment-refractory cancer.Trial registration#NCT02449538, April 2015.

BackgroundMore than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC.MethodsWe investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes.ResultsBRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS.ConclusionThe result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC.

BackgroundThe aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.MethodsPatients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000 mg/m2 twice daily + D1 cisplatin 75 mg/m2, every 3 weeks) or the CP arm (D1–14 capecitabine 1000 mg/m2 twice daily + D1, 8 paclitaxel 80 mg/m2, every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life.ResultsA total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0–6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9–8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2–11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4–17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms.ConclusionsBoth CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.

Background

In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied.

Methods

Between July 1^st and November 30^th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC) were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS) score.

Results

In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trials was substantially higher in patients who had a higher level of education (p<0.001), were married (p=0.004), and had a higher economic status (p=0.001). However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%). Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p<0.001).

Conclusions

This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.