Oxaliplatin-containing Regimen Research Articles

Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma.

There is no established salvage regimen for pediatric patients with relapsed nasopharyngeal carcinoma (NPC) and outcomes are dismal. We performed a multicenter retrospective review to determine outcomes after first salvage therapy for pediatric patients with relapsed NPC. Fourteen patients were treated with varied regimens. Two of the 14 patients received oxaliplatin-containing regimens and achieved a long-term complete response. Although definitive recommendations cannot be made based on outcomes for 14 patients who received varied regimens, we discuss justification for an oxaliplatin-containing regimen in combination with gemcitabine as a reasonable choice for first-line salvage therapy for pediatric patients with relapsed NPC.

Risk factors for oxaliplatin-induced vascular pain in patients with colorectal cancer and comparison of the efficacy of preventive methods

BackgroundVascular pain is a common adverse drug reaction in colorectal cancer patients receiving peripheral venous administration of oxaliplatin. The aim of this work was to identify risk factors for vascular pain, and to examine whether currently used treatments reduce its incidence.MethodsWe conducted a multicenter retrospective study in Japanese colorectal cancer patients receiving peripheral venous administration of oxaliplatin. The effects of various treatments (administration of analgesics, addition of dexamethasone to the infusion solution for pH adjustment, dilution of the infusion solution, or use of hot gel for warming the injection site) on the incidence of vascular pain were assessed. Risk factors for vascular pain were identified by multiple logistic regression analysis.ResultsOne hundred and ninety patients who had received an oxaliplatin-containing regimen via a peripheral venous route were analyzed. None of the preventive methods examined significantly reduced the incidence of vascular pain. BMI (BMI < 22), clinical stage (I-III) and oxaliplatin dosage (130 mg/m2 versus dose reduction) were identified as independent risk factors for development of vascular pain. The incidence of oxaliplatin-induced vascular pain was significantly higher in patients who had two or more risk factors.ConclusionsBMI, clinical stage and oxaliplatin dosage were identified as independent predictive markers for oxaliplatin-induced vascular pain. Existing treatments for vascular pain are not effective in reducing its incidence.

Rechallenge of oxaliplatin-containing regimens in the third- or later-line therapy for patients with heavily treated metastatic colorectal cancer.

PurposeThe third- or later-line therapy available often yield poor survival benefit in patients metastatic colorectal cancer (mCRC). The retrospective study aimed to evaluate efficacy of rechallenge of oxaliplatin-containing regimens.Patients and methodsPatients with mCRC who progressed from fluoropyrimidine, oxaliplatin, and irinotecan in the first- and second-line chemotherapy, were treated by reexposure to oxaliplatin-containing regimen. Patients treated by anti-epidermal growth factor receptor (EGFR) antibodies with irinotecan were included in the control arm.ResultsNinety-five and 29 patients were treated with either oxaliplatin reexposure or anti-EGFR antibodies with irinotecan, respectively, as the third- or later-line therapy. The median time to treatment failure (TTF) and overall survival (OS) was 3.77 and 12.17 months in the oxaliplatin arm, with 4.77 months of TTF and 11.37 months of OS in the control arm; there was no significance between the 2 arms (p>0.05). Oxaliplatin reexposure resulted in 6.3% objective response rate with no complete response, 6 partial response, 39 stable disease, and 37 progressive disease. The disease control rate was 47.4% (45/95). The multivariate analysis found that patients who achieved disease control by oxaliplatin reexposure had a superior TTF (6.13 vs 1.7 months, p<0.001) and OS (15.73 vs 6.27 months, p<0.001) compared with those presenting with progressive disease.ConclusionThis study showed that rechallenge of oxaliplatin-containing chemotherapy in the third- or later-line therapy may lead to tumor control and improved survival in mCRC patients, which was equivalent to that of anti-EGFR antibodies with irinotecan.Clinical significanceRechallenge of oxaliplatin-containing regimens in the third- or later-line of therapy is a common practice, despite few evidence available. The present study found that rechallenge of oxaliplatin-containing regimens produced equivalent tumor control and survival benefit to that of anti-EGFR antibodies with irinotecan in mCRC.

Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer

BackgroundCapecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort. Patients and MethodsWe identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen. RDI was defined as the total dose received divided by the intended total dose if all cycles were received. ResultsFOLFOX was associated with increased mucositis (6.2% vs. 0.7%, P = .0069) and neutropenia (25.9% vs. 8.6%, P < .0001), while CAPOX was associated with increased dose-limiting toxicities (DLTs) (90.7% vs. 80.2%, P = .0055), diarrhea (31.8% vs. 9.0%, P < .0001), and hand–foot syndrome (19.9% vs. 2.1%, P < .0001). Higher median RDI of fluoropyrimidine (93.7% vs. 80.0%, P < .0001) and oxaliplatin (87.2% vs. 76.3%, P < .0001) was noted for patients receiving FOLFOX. Reducing the duration from 6 to 3 months would have prevented 28.7% of FOLFOX and 20.5% of CAPOX patients from ever experiencing a DLT (P = .0008). Overall survival did not differ by regimen (hazard ratio = 0.73; 95% confidence interval 0.45-1.22; P = .24). However, CAPOX was associated with improved disease-free survival (3-year disease-free survival 83.8% vs. 73.4%, P = .022), which remained significant in high-risk (T4 or N2) (P = .039) but not low-risk patients (P = .19). ConclusionCAPOX may be associated with improved disease-free survival despite greater toxicities and lower RDI. Reducing adjuvant chemotherapy duration to 3 months would prevent 26% of patients from ever experiencing a DLT.

Chemotherapy for advanced gastric cancer.

Chemotherapy for advanced gastric cancer.

A pilot study of lactoferrin in patients with self-reported, chemotherapy-induced taste and smell abnormalities.

e21643 Background: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to food avoidance, altered nutritional intake, treatment delay or withdrawal, diminished socialization and impaired overall quality of life. Lipid peroxidation of mucosal cell membranes in the oral cavity is one cause of TSA and lactoferrin (LFN), an iron-binding protein normally present in saliva, is an effective scavenger of lipid byproducts that can decrease metallic flavor in healthy volunteers. Methods: Eligible patients with colorectal or pancreatic adenocarcinoma and self-reported TSA while on an oxaliplatin-containing chemotherapy regimen were treated with LFN 250mg three times daily for 4 weeks and then followed for an additional 4 weeks off study drug. A second identical IRB-approved pilot trial enrolled patients with solid tumors, lymphoma or myeloma with self-reported TSA while receiving chemotherapy. The primary outcome was the change in self-reported TSA following 4 weeks of LFN as measured by a validated taste and smell questionnaire (TSQ) consisting of taste (score 0-10) and smell (score 0-6) subscales, which are combined to yield a total composite score (0-16, 0 = no TSA). The TSQ was assessed at 0, 4 and 8 weeks along with the FAACT (FACT–G + anorexia subscale), salivary protein and metals analyses, and the Brief Smell Identification test (B-SIT). Results: 26 total pts were enrolled (14 Males; mean age 60.5 years; range 32-79), and 19 and 17 pts remained on study with analyzable data at 4 and 8 weeks. Baseline mean taste, smell and composite TSQ scores for the 26 enrolled patients were 6.5, 3.1 and 9.6 units. After 4 weeks of LFN treatment, the mean overall TSQ score improved by 1.7 units (p = .018) while the taste and smell subscales improved by 0.6 (p = .062) and 1.1 units (p = .042) respectively. At 8 weeks, the mean TSQ score improved from baseline by 3.8 units (p &lt; .0001) while the taste and smell subscales improved by 1.9 (p = .001) and 1.8 (p = .003) units. No significant change from baseline was recorded in the FAACT or the B-SIT at 4 or 8 weeks. Conclusions: These pilot data suggest that further evaluation of LFN in patients with self-reported TSA is warranted. A randomized trial is in development. Clinical trial information: NCT01941810, NCT01596634.

N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2.

N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Cα (PKCα), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion, NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.

REOX: Evaluation of the Efficacy of Retreatment With an Oxaliplatin-containing Regimen in Metastatic Colorectal Cancer: A Retrospective Single-center Study

BackgroundTreatment of metastatic colorectal adenocarcinoma (mCRC) has evolved, and survival is over 30 months in contemporary trials. Nevertheless, there is a paucity of effective regimes after the first or second-line treatment. Thus, reexposure to previously used drugs has become a treatment strategy for some patients. We aimed to evaluate the efficacy of retreatment with an oxaliplatin-containing regimen in mCRC and correlate this with clinicopathologic features. Patients and MethodsWe retrospectively analyzed 83 patients with mCRC who underwent reexposure to oxaliplatin (REOX). REOX was defined as a second trial of an oxaliplatin-containing regimen after a previous failure. Primary endpoint was time to treatment failure (TTF). ResultsThe median age was 53.5 years, and the female/male ratio was 51.8%/48.2%. The site of the primary tumor was colon (67.5%) and rectal (32.5%). KRAS was mutated in 39.8%. Liver-limited metastasis was found in 19.3% of patients. The main regimen was 5-fluorouracil, levoleucovorin, and oxaliplatin (mFOLFOX6) (84.3%). Bevacizumab and cetuximab were used in 42.2% and 6% of patients, respectively. REOX was used in the third and fourth lines in 48.2% and 25.3% of patients, respectively. The median TTF after REOX was 6.04 months. Overall survival (OS) was 10.04 months. Disease control (complete response + partial response + stable disease) was observed in 56.6%, whereas 42.2% had progressive disease. Partial response + complete response to previous oxaliplatin was predictive of prolonged OS. Patients who attained disease control had better median OS compared with those with progressive disease (14.5 vs. 6.24 months; P < .0001). ConclusionIn the setting of heavily pretreated patients with mCRC, REOX was an effective treatment, with mTTF of 6.04 months in our cohort. Selection of patients with the longest time since previous oxaliplatin can translate in better outcome. Further studies should be conducted to confirm our data.

Perioperative Chemotherapy in Elderly Patients with Locally Advanced Adenocarcinoma of the Stomach and the Esophagogastric Junction: A Retrospective Cohort Analysis of Toxicity and Efficacy at the National Center for Tumor Diseases, Heidelberg

Objective: Esophagogastric cancer occurs more frequently in older patients, but these are underrepresented in clinical studies establishing the current treatment standards for perioperative chemotherapy in locally advanced disease. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens. Methods: Using a prospectively generated database, we analyzed 63 patients aged ≥70 years undergoing perioperative chemotherapy for locally advanced esophagogastric cancer. The information included Eastern Cooperative Oncology Group (ECOG) performance status, comorbidity index, body mass index, regimen of chemotherapy, toxicity, dosage adjustments, date of surgery, application of adjuvant treatment, date of progression, and date of death. Survival times were calculated. Results: The median age was 73 years. 96.8% of the patients received an oxaliplatin-containing regimen. In 17.5% of the patients, the dosage was reduced, and treatment was previously permanently stopped in 7.9%; 80% of the patients underwent curatively intended surgery, but only 27.5% of those undergoing resection started adjuvant treatment. Major histological regression was observed in 21.6% of the patients. The median survival was 19.1 months. Significantly improved survival times were observed for patients undergoing surgery (p = 0.008) and for patients with a triplet therapy (p = 0.004). Survival was worse for patients aged ≥75 years. Conclusion: perioperative treatment is feasible and effective in elderly patients with esophagogastric cancer.

North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).

807 Background: FOLFOX and XELOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for Japanese patients(pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 3-year DFS rate. Results: From Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age ; 65(33-84), Male/female ; 131/134, PS 0/1 ; 258/7, stage IIIA/IIIB/IIIC ; 37/197/31, colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year DFS rate was 75.2 percent (95% confidence interval, 69.6 to 80.0). Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation (81.2%). However, the 3-year DFS rate in this trial was similar to several pivotal trials. We plan to do subset analysis. Clinical trial information: UMIN000004590.

261P Efficacy of chemotherapy in patients with unresectable or metastatic pancreatic acinar cell carcinoma: Potentially improved efficacy with oxaliplatin-containing regimen

261P Efficacy of chemotherapy in patients with unresectable or metastatic pancreatic acinar cell carcinoma: Potentially improved efficacy with oxaliplatin-containing regimen

261P Efficacy of chemotherapy in patients with unresectable or metastatic pancreatic acinar cell carcinoma: Potentially improved efficacy with oxaliplatin-containing regimen

261P Efficacy of chemotherapy in patients with unresectable or metastatic pancreatic acinar cell carcinoma: Potentially improved efficacy with oxaliplatin-containing regimen

Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen.

PurposePancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy.Materials and MethodsBetween January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea.ResultsThe median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second-line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029).ConclusionOur results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.

Cost-minimization analysis of adjuvant chemotherapy regimens given to patients with colorectal cancer in Japan.

BackgroundConsideration of medical costs as well as effectiveness and adverse events is rapidly been becoming an important factor in the selection of chemotherapy regimens. However, practical data on the costs of chemotherapy are scarce. We clinically estimated the medical costs of 6 adjuvant chemotherapy regimens for colorectal cancer on the basis of clinical and cost-related data and compared their cost-effectiveness by cost-minimization analyses.MethodsAll patients who received adjuvant chemotherapy for colorectal cancer between April 2012 and May 2015 at four hospitals affiliated with Showa University were studied retrospectively. Clinical and cost data related to adjuvant chemotherapy were collected from medical records and medical fee receipt data, respectively. Six adjuvant chemotherapy regimens were studied: capecitabine and oxaliplatin (CapeOX); 5-fluorouracil (5-FU), ℓ-leucovorin (LV), and oxaliplatin (modified FOLFOX6 [mFOLFOX6]); 5-FU and LV (5-FU/LV); tegafur and uracil (UFT), and LV (UFT/LV); capecitabine; and tegafur, gimeracil and oteracil (S-1). The regimens were divided into 2 groups according to whether or not they contained oxaliplatin because of the difference in effectiveness. Cost-minimization analyses, where relative costs of regimens showing equivalent effectiveness were simply compared, were performed to evaluate the cost-effectiveness of the regimens in each group.ResultsA total of 154 patients with colorectal cancer received adjuvant chemotherapy during the study period. Fifty-seven patients were treated with CapeOX, 10 with mFOLFOX6, 38 with UFT/LV, 20 with capecitabine, and 29 with S-1. No patient received 5-FU/LV. The total costs of oxaliplatin-containing regimens were significantly higher than those of oxaliplatin non-containing regimens. The high cost of oxaliplatin, but not the costs of drugs or various tests for the treatment of adverse events, was the primary reason for the higher costs of the oxaliplatin-containing regimens. The cost-effectiveness of the oxaliplatin-containing regimens CapeOX and mFOLFOX6 were comparable. Among the oxaliplatin non-containing regimens, the cost-effectiveness of S-1 and capecitabine was superior to that of UFT/LV.ConclusionThus, we provided the cost-effectiveness data of 5 adjuvant chemotherapy regimens for colorectal cancer based on practical clinical and cost data from Japanese patients. The results can be included as a factor in regimen selection because these results would represent the real world.Trial registrationThis study is a retrospective observational study and does not include any health care interventions. Therefore, we did not register the protocol of this study.

Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma.

Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1% of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12months) observed in 6 out of 7 patients (86%). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58%), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

Reconsidering the benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer.

Colorectal cancer is one of the most frequent solid tumors in the western world, with low survival rates in patients with metastatic disease. Doublet chemotherapy regimens such as FOLFOX or FOLFIRI are the mainstay of standard first-line chemotherapy in the metastatic setting. The conventional treatment as a first-line approach is continuous application until progression or intolerable toxicities. However, only one third of patients are treated until progression mainly due to the side effects of chemotherapy. Notably, oxaliplatin-containing regimens such as FOLFOX/CapOx or FOLFOXIRI are associated with oxaliplatin-induced neuropathy, which is the main reason for treatment discontinuation or treatment de-escalation. On this basis, recent studies have investigated the clinical benefits of bevacizumab-based intermittent and continuous treatment regimens in the metastatic colorectal setting, together with various strategies to optimize maintenance therapy including regimens with targeted therapies, such as cetuximab, ziv-aflibercept and regorafenib. Recent studies have also investigated when maintenance therapy should be initiated as well individualizing treatment based on patient, tumor and treatment characteristics, as well as molecular biomarkers. This article reviews the current evidence for the clinical benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer, and also evaluates the effect of RAS and BRAF mutational status on maintenance strategies.

The ATOM trial: A multicenter, randomized phase II study of modified FOLFOX6 plus bevacizumab and modified FOLFOX6 plus cetuximab for colorectal cancer with liver-limited metastases.

TPS777 Background: It remains unresolved which antibody, anti-vascular endothelial growth factor or anti-epidermal growth factor receptor antibody, is the best targeted agent to combine with chemotherapy for patients having liver-limited metastases of KRAS Exon 2 or RAS wild-type colorectal cancer. Methods: The ATOM trial is a Japanese multicenter, randomized phase II study comparing modified FOLFOX6 plus bevacizumab with modified FOLFOX6 plus cetuximab in patients with unsuitable liver metastases for resection (5 or more liver metastatic lesions and/or maximum tumor diameter &gt; 5cm). Patients are enrolled and randomly assigned to receive either treatment in 1:1 ratio from May 2013 to April 2016. Stratification factors for randomization are synchronous or metachronous liver metastases, number (1–4 or ≥ 5) and size ( ≤ 5 cm or &gt; 5 cm) of metastatic lesions, and adjuvant chemotherapy with or without oxaliplatin-containing regimen. All patients are to be followed up to March 2017. Primary endpoint is progression-free survival (PFS). We employed a selection design based on hazard ratios. Planned sample size is 120 patients with 84 estimated PFS events based on the hypothesis to select the superior treatment with the 75.0 % selection probability if the difference of both treatments is a 1-year PFS rate of 5% and the inferior treatment has a 1-year PFS rate of 50%. Secondary endpoints are response rate, tumor shrinkage at week 8, liver resection rate, time to treatment failure, overall survival, quality of life, and adverse events. Exploratory endpoints include pathologic and morphologic assessments, which will be investigated in collaboration with radiologists and pathologists. The plasma factors relating to tumor angiogenesis are assessed sequentially to explore the association with treatment efficacies. As of Aug 20th 2015, 102 patients were enrolled. The results from this trial will show which targeted agents should be used to treat liver-limited diseases from colorectal cancer with WT RAS tumor. Clinical trial information: NCT01836653.

Efficacy of chemotherapy in patients with pancreatic acinar cell carcinoma.

308 Background: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, efficacy of chemotherapy in this patient population still remains largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with pancreatic ACC who received chemotherapy. Methods: Between January 1997 and March 2015, a total of 22 patients with histologically confirmed locally advanced unresectable or metastatic pancreatic ACC were identified in Asan Medical Center, Seoul, Korea. Among them, 15 patients received chemotherapy and 2 patients with locally advanced disease underwent concurrent chemoradiotherapy followed by chemotherapy; these 17 patients were included in this analysis. Results: Median age was 58 year old (range, 29-72), and 15 patients (88%) were male. Mixed acinar-neuroendocrine tumor and mixed acinar-adenocarcinoma was found in 1 (6%) and 2 (12%) patients, respectively. The most common metastatic site was liver (n = 9, 53%), followed by intraabdominal lymph nodes (n = 5, 29%), and peritoneum (n = 3, 18%). As 1st-line therapy, 5-FU or its derivative were given in 7 patients (41%), gemcitabine in 6 (35%), gemcitabine plus capecitabine in 2 (12%) and FOLFOX in 2 (12%). Objective response rate (ORR) was 30% and median time-to-progression (TTP) was 5.8 months (95% CI, 2.9-8.6). After progression, 2nd-line chemotherapy was given in 9 patients; 5 and 4 patients received FOLFOX and gemcitabine, respectively. On 2nd-line chemotherapy, ORR was 44% and median TTP was 6.3 months (95% CI, 0.3-12.4); patients with FOLFOX had significantly better TTP compared to those with gemcitabine (median 6.5 vs 1.4 months, p = 0.003). The ratio of TTP at 1st-line chemotherapy to TTP at 2nd-line chemotherapy was significantly higher in patients with FOLFOX (2.10 [range, 0.16-8.30] compared to those with gemcitabine (0.12 [0.08-0.25]; p = 0.03). Median overall survival in all patients was 16.9 months (95% CI, 14.4-19.4). Conclusions: Pancreatic ACC seems to have better prognosis compared to pancreatic adenocarcinoma. Our results suggest that oxaliplatin-containing regimen may have improved activity against pancreatic ACC.

Progression of systemic chemotherapy with oxaliplatin-containing regimens for advanced hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) characterized by insidious onset is a highly invasive malignance and has a rapid progress. The majority of patients, especially in Asian countries, present with locally advanced or distant metastatic disease at diagnosis and are not eligible for local treatment. Before the publication of the EACH study results showing the survival benefits of the FOLFOX 4 regimen in Chinese patients with advanced HCC, no chemotherapeutical drug or regimen was considered as systemic chemotherapy standard for this group of patients due to the lack of evidence-based recommendations. Oxaliplatin-containing regimens have shown clinical activity against advanced HCC with an acceptable safety profile. The aim of this article is to present a review of the scientific evidence mainly originating from China that supports the recommendation of oxaliplatin-based regimens for the treatment of Chinese patients with advanced HCC.

Celecoxib antagonizes the cytotoxicity of oxaliplatin in human esophageal cancer cells by impairing the drug influx

It has been demonstrated that COX-2-selective inhibitor celecoxib shows synergy with oxaliplatin for suppressing tumor growth. However, the benefit of adding celecoxib to oxaliplatin-based regimen in human esophageal cancer is largely unknown. In the present study, we demonstrated that celecoxib antagonized oxaliplatin-induced cytotoxicity and apoptosis independent of COX-2 inhibition in human esophageal cancer cells. Celecoxib decreased cellular oxaliplatin accumulation and Pt-DNA adduction formation due to reduced drug influx. Celecoxib alone or combined with oxaliplatin substantially reduced the expression of organic cation transporter 2 (OCT2). To this end, OCT2 knockdown was sufficient to reduce oxaliplatin uptake, connecting OCT2 expression to oxaliplatin accumulation. Moreover, oxaliplatin combined with celecoxib also showed no beneficial effect when compared with monotherapy in esophageal cancer cell-xenografted nude mice. To conclude, our data provide evidence that the addition of celecoxib to oxaliplatin-containing regimens for patients with OCT2-expressing cancers should be cautious.