Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim
Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017
Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.
Citations
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Purpose
Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer.
Materials and Methods
For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated.
Results
Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated.
Conclusion
High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.
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Purpose This study was conducted to validate the survival benefit of metastasectomy plus chemotherapy over chemotherapy alone for treatment of Krukenberg tumors from gastric cancer and to identify prognostic factors for survival. Materials and Methods Clinical data from 216 patients with Krukenberg tumors from gastric cancer were collected. Patients were divided into two arms according to treatment modality: arm A, metastasectomy plus chemotherapy and arm B, chemotherapy alone. Results Overall survival (OS) was significantly increased in arm A relative to arm B for patients initially diagnosed with stage IV gastric cancer (18.0 months vs. 8.0 months; p < 0.001) and those with recurrent Krukenberg tumors (19.0 months vs. 9.0 months; p=0.002), respectively. Metastasectomy (hazard ratio [HR], 0.458; 95% confidence interval [CI], 0.287 to 0.732; p=0.001), signet-ring cell pathology (HR, 1.583; 95% CI, 1.057 to 2.371; p=0.026), and peritoneal carcinomatosis (HR, 3.081; 95% CI, 1.610 to 5.895; p=0.001) were significant prognostic factors for survival. Conclusion Metastasectomy plus chemotherapy offers superior OS when compared to palliative chemotherapy alone in gastric cancer with Krukenberg tumor. Prolonged survival applies to all patients, regardless of gastric cancer stage. Metastasectomy, signet-ring cell pathology, and peritoneal carcinomatosis were prognostic factors for survival. Future prospective randomized trials are needed to confirm the optimal treatment strategy for Krukenberg tumors from gastric cancer.
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Purpose The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy—gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)—in patients with advanced pancreatic cancer. Materials and Methods There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and capecitabine 850 mg/m2 twice daily for 2 weeks followed by 1 week’s rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. Results The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. Conclusion GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.
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Gemcitabine–erlotinib versus gemcitabine–erlotinib–capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group Antonio Irigoyen, Javier Gallego, Carmen Guillén Ponce, Ruth Vera, Vega Iranzo, Inmaculada Ales, Sara Arévalo, Aleydis Pisa, Marta Martín, Antonieta Salud, Esther Falcó, Alberto Sáenz, José Luis Manzano Mozo, Gema Pulido, Joaquina Martínez Galán, Roberto European Journal of Cancer.2017; 75: 73. CrossRef
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PURPOSE The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response. MATERIALS AND METHODS Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study.
Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI. RESULTS The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy. CONCLUSION It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles.
Development of individualized chemotherapy regimens based on gene expression profiles is warranted.
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