Oxaliplatin Capecitabine Research Articles

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors

Purpose: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin

Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin

Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer

BackgroundThe treatment of patients with metastatic colorectal cancer (mCRC) has evolved during the past 2 decades, and patient survival has increased. Consequently, patients are exposed to more chemotherapeutic agents and regimens. Little is known about therapeutic drug sequencing and the factors influencing these choices. Materials and MethodsAn observational, retrospective medical record review was conducted of patients with newly diagnosed adult mCRC from January 2002 to September 2013 identified in the McGill University-Jewish General Hospital's local tumor registry. All patients presented with mCRC (stage IV) and received ≥ 2 cycles and/or ≥ 28 days of first-line chemotherapy. The patient demographics, CRC characteristics, treatment patterns, and outcomes were recorded. The reason for changing or halting therapy was also reported. ResultsOf the 215 patients who underwent treatment, 74.4% received second-line, 36% third-line, and 16.3% fourth-line treatment. In total, 88% received ≥ 3 classes of cytotoxic chemotherapy and 80% received ≥ 1 biologic agent. The most common first-line treatment was FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) (47.4%) or CAPOX (capecitabine, oxaliplatin) (28.8%), and more than one half received bevacizumab (56%). Among the second- and third-line treatments, FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) was the most common (40.3% and 30.3%, respectively), and bevacizumab was the most frequently used biologic agent (48.1% and 39.2%, respectively). For fourth-line treatment and beyond, most patients participated in clinical trials (45.7%) or received panitumumab monotherapy (31.4%). Across the first 4 therapy lines, disease progression was the primary motive for discontinuation (39.5%, 53.8%, 58.2%, and 37.1%). ConclusionFOLFOX was the most common first-line and FOLFIRI the most common second- and third-line mCRC therapy. Bevacizumab was the most frequently used targeted therapy across all 3 treatment lines. Therapy discontinuation was primarily due to disease progression.

Oxaliplatin-Induced Dysphonia and Dysarthria - A Case Report

Oxaliplatin is a new, third-generation platinum complex. It has a good safety profile characterized by low haematological-gastrointestinal toxicity. It is commonly used in combination with 5-fluorouracil and folinic acid in the treatment of colorectal cancer. Neurotoxicity in the form of peripheral neuropathy is the most common side effect. However dysphonia and dysarthria are very rarely seen. Here, we report a 54 year old female patient who presented with carcinoma colon. She underwent right hemicolectomy. CT scan abdomen showed stage 4 disease with multiple metastatic deposits in the liver. She was started on chemotherapy with CAPOX (Capecitabine/oxaliplatin). She tolerated well during the first cycle. After 2nd cycle, she developed diarrhoea and cellulitis and 3rd cycle was delayed. During the 3rd cycle, she complained of pain and spasm of jaw muscle and her voice was very feeble, which lasted for 1 hour even after the infusion was stopped. She was then prescribed half tablet of clonazepam 0.5mg and sedated; it took almost 15minutes more for relief followed by chemotherapy. In a study conducted by Netherlands Pharmacovigilance Centre, 4 such cases of laryngospasm in association with the use of oxaliplatin reported. This can be managed by stopping the use of oxaliplatin and replacing with hydrocortisone, chlorpheniramine and lorazepam. The acute reversible pattern of sensory neuropathy was observed in about 56% of study patients who received Oxaliplatin with 5-fluorouracil. Neurotoxicity is the dose-limiting side effect with this drug. This side effect can manifest as two distinct forms: the acute, reversible sensory neuropathy and a chronic, cumulative neuropathy. The acute form occurs with infusion while the chronic toxicity does not become apparent until 8-10 cycles. The treatment of oxaliplatin-induced neurotoxicity needs to start at the bedside. Nursing staff and oncologists should inform patients to avoid drinking cold beverages. This can prevent pseudolaryngospasm. Promising strategies exist that include dosing modification, increasing infusion time and neuromodulatory agents which include Ca/Mg infusion, glutathione, carbamazepine, gabapentine, and amifostine.

Utilization of capecitabine-oxaliplatin (CAPOX) versus infusional 5-fluorouracil and oxaliplatin (FFOX) in the adjuvant treatment (AT) of resected high-risk colon cancer.

e14696 Background: Patients with high-risk Stage II or Stage III colon cancer are candidates for adjuvant chemotherapy with CAPOX or mFOLFOX6. Our primary outcome was to identify the utilization ra...

DeFazio capsules oxaliplatin neoadjuvant chemotherapy on matrix metalloproteinase-9 and vascular endothe-lial growth factor in patients with advanced gastric cancer

Objective To study DeFazio capsules oxaliplatin neoadjuvant chemotherapy on matrix metallo-proteinase-9 （ MMP-9 ） and vascular endothelial growth factor （ VEGF ） in patients with advanced gastric cancer . Methods 92 patients with advanced gastric cancer were randomly divided into the two groups ,the observation group （ n=46 ） and the control group （ n=46 ） .Both two groups were used neoadjuvant chemotherapy , DeFazio capsules oxaliplatin chemotherapy for the observation group and capecitabine oxaliplatin chemotherapy for the control group . Expression of MMP-9 and VEGF was determined by immunohistochemistry in gastric cancer tissues .Results After chemotherapy,the total effective rate was 60.9%in the control group and 80.4%in the observation group.The total effective rate of the observation group was significantly higher （χ2 =6.42,P〈0.05）.The anemia,thrombocyto-penia,hepatic dysfunction ,renal dysfunction ,the incidence of nausea and vomiting had no significant differences be-tween the two groups （χ2 =1.52,0.96,2.06,0.00,1.28,all P〉0.05）.Neutropenia,neurotoxicity in the observation group were less than the control group （χ2 =5.68,4.18,all P〈0.05）.Before chemotherapy,the positive rates of VEGF and MMP-9 expression in the control group were 93.5%,78.3%.Those of the observation group were 89.1%and 82.6%,respectively,the differences were not significant （χ2 =2.12,2,72,all P〉0.05）.After the chemothera-py,the positive expression rates of VEGF and MMP-9 in the control group were 45.7%,41.3%,respectively.Those of the observation group were 23.9%and 21.7%,respectively.VEGF and MMP-9 positive expression rates were sig-nificantly lower than before chemotherapy （χ2 =4.72,4.08,10.14,9.84,P〈0.05,P〈0.01）.The observation group was significantly lower than the control group （χ2 =5.14,4.72,all P〈0.05）.Conclusion DeFazio capsules oxali-platin neoadjuvant chemotherapy can decrease MMP-9 and VEGF expression in patients with advanced gastric cancer . Key words: Stomach neoplasms ; Chemoradiotherapy, adjuvant ; Matrix metalloproteinase 9 ; Vascular endothe-lial growth factors

A New Predictive Molecular Marker for Cetuximab Benefit in Rectal Cancer?

Sclafani et al present data and suggest that tumor protein 53 (TP53) may be a predictive marker of cetuximab benefit in patients with rectal cancer undergoing neoadjuvant chemoradiation in this issue of the Journal (1). This article relies on an unplanned, retrospective analysis of molecular marker data on a subset of patients participating in the randomized phase II EXPERT-C clinical trial initially reported in 2012 (2). Patients with operable magnetic resonance imaging– defined high-risk rectal cancer received four cycles of capecitabine/ oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX-C). The primary endpoint was complete tumor response, which was modified during conduct of the study to include only the subset of patients whose tumors were KRAS/BRAF wild type. This was quite reasonably done when the impact of KRAS status on antitumor activity of epidermal growth factor receptor (EGFR)-inhibiting monoclonal antibodies was documented (3). However, the sample size of the study was not increased to assure the intended statistical power. One hundred and fifty eligible patients were randomly assigned. Based on a subset of patients with KRAS/BRAF wild-type tumors (46 patients who received cetuximab vs 44 patients who did not receive cetuximab as a component of treatment), the authors concluded that cetuximab led to a statistically significant increase in response rate and overall survival, but the primary end point of improved complete pathologic response was not met. Further follow-up revealed that contrary to the initial report, adding cetuximab was not associated with a statistically significant improvement in progression-free survival or overall survival in either KRAS/BRAF wild-type or unselected

Positron emission tomography/computed tomography for early treatment response evaluation in metastatic colon cancer.

614 Background: Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/ computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases type 1 (TIMP-1), carcinoembryonic antigen (CEA) and urokinase plasminogen activator receptor domain I [uPAR(I)] for early assessment of treatment response in mCC patients. Methods: Thirty-three mCC patients scheduled for first line chemotherapy with capecitabine, oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria In Solid Tumours (RECIST1.1) and EORTC PET criteria. Plasma TIMP-1, plasma uPAR(I) and serum CEA were determined. Results: Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80 %, specificity of 69 % and an Odds Ratio of 13.9 [CI 1.9; 182]. Early metabolically stable or progressive disease was associated with shorter progression-free survival (PFS) (hazard ratio (HR) = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated to shorter PFS (TIMP-1 per unit increase on a log-2 transformed ng/mL scale: HR = 2.23 [CI 1.20; 4.14]; uPAR(I) per 25 fmol/mL increase: HR = 1.36 [CI 1.03; 1.79]). Conclusions: This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1 and uPAR(I) guided early treatment adaptation in mCC.

Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

BackgroundTo evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. Patients and methodsAdults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m2, day 1) intravenously and capecitabine (1000 mg/m2 twice daily orally, days 1–14) for up to six cycles. Surgery was carried out 6–8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. ResultsOf 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%–90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%–84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. ConclusionsRadical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab–capecitabine–oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Clinical study of oxaliplatin plus TS-1 or capecitabine in the treatment of advanced colon cancer

Objective To investigate the clinical efficacy and safety of two chemotherapy regimens based on oxaliplatin combined with TS-1 or capecitabine in the treatment of advanced colon cancer.Methods 53 advanced colon cancer patients were involved in this study.26 patients were given the regimen of SOX:oxaliplatin (130 mg/m2) was administered intravenously in three hours on day 1,while S-1 (40 mg/m2) was administered orally twice daily for 14 consecutive days.27 patients were given the regimen of XELOX:oxaliplatin capecitabine was administered intravenously in three hours on day 1,while capecitabine (1000 mg/m2)was administered orally twice daily for 14 consecutive days.The regimens were repeated every 3 weeks.The efficacy and toxicy were evaluated after 2 cycles teatment.Results All the 53 patients were eligible for enrollment and the patients were appreciable for efficacy and toxicy.The objective response rates (RR) were 46.1％ (12/26) and 48.1％ (13/27) in the SOX group and XELOX group respectively.The disease control rates (DCR) were 76.9 ％ (20/26) and 74.1％ (20/27).There was no significant difference in RR.The objective side effects associated with the two regimens were bone marrow suppressive,digestive system reaction (diarrhea or vomiting),peripheral neuropathy and hand-foot syndrome on mostly graded 1 or 2.Compared to the XELOX group,nausea vomiting of the SOX group were higher (x2 =4.462,P =0.035),but diarrhea and hand-foot syndrome of XELOX group was obviously higher than that of SOX group [44.4 ％ (12/27) vs.19.2 ％ (5/26) (x2 =4.366,P =0.001),44.4 ％ (12/27) vs.3.8 ％ (1/26) (x2 =11.699,P=0.037)].Conclusion There are no significant difference in the efficacy of the two chemotherapy regimens and the side toxicities are all well tolerable. Key words: Intestinal neoplasms; TS-1; Oxaliplatin; Capecitabine; Drug therapy, combination

605P - Phase II Trial of Panitumumab in Combination with Oxaliplatin and Capecitabine Chemotherapy as 1st Line Therapy in Patients with Colorectal Cancer and Advanced Liver Metastases: The Metapan Study

ABSTRACT Background Preoperative chemotherapy improves outcome in potentially resectable colorectal cancer with liver metastases. We evaluated the activity of a neoadiuvant treatment with capecitabine–oxaliplatin (XELOX) associated with the anti-EGFR antibody Panitumumab in patients with unresectable, liver-only, metastatic colorectal cancer (CRC). Patients and methods Chemotherapy-naive patients with unresectable liver metastases of CRC and no other metastatic sites were enrolled. Criteria of unresectability were defined as: more than 3 liver metastases including > 50% hepatic involvement and requiring a major hepatectomy with controlateral wedge resection or any metastases requiring a resection that does not preserve two contiguous hepatic segments. Since November 2008 only patients bearing wild type KRAS were included. All patients received neoadjuvant XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every four cycles. Primary endpoint was radiological objective response rate (ORR). Secondary endpoints were overall survival (OS), progression free survival (PFS), percentage of patients whose disease became radically resectable, and safety. Results Forty-nine patients were recruited, of which 35 were KRAS wild type, and 14 (enrolled before study amendment), were unknown (9 patients) or mutated (5 patients). Forty-six were evaluable for response. Following neoadjuvant P-XELOX, the ORR in the general population was 54%, with 3 CR, 22 PR, 14 SD. In wild type KRAS patients ORR reached 65% (3 CR, 18 PR, 7 SD), and this allowed 15 patients with initial unresectable liver metastasis to be converted to resectability. Survival analysis showed median PFS and OS of 8.5 months and 22.1 months, respectively. Resected patients had significantly better OS if compared to unresected (p = 0.00014). The most common toxicities were cutaneous, gastrointestinal, and neurologic. Conclusion Neoadjuvant P-XELOX yields high response rates for patients with metastatic CRC and extensive liver involvement, and leads to remarkable conversion to resectability of liver metastasis. Disclosure All authors have declared no conflicts of interest.

Correlation of bevacizumab-induced hypertension and outcome in the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection

Background:Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer, but to date, despite extensive research, no predictive or prognostic biomarkers for bevacizumab have been identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictive biomarker.Methods:Blood pressure was recorded during the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection. In this analysis, the development of bevacizumab-induced hypertension was correlated with clinical outcomes.Results:Fifteen percent of patients developed ⩾grade 1 hypertension while receiving neoadjuvant chemotherapy, and 4% developed grade 3 hypertension. There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not.Conclusion:Bevacizumab-induced hypertension did not predict radiological response or survival in our study. The results highlight a number of important issues regarding the use of hypertension as a biomarker.

Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)

To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Adjuvant chemotherapy after D2 gastrectomy for gastric cancer

In the CLASSIC study, capecitabine–oxaliplatin was an effective chemotherapy after D2 gastrectomy for stage II–IIIB gastric cancer. We compared these data with the ACTS-GC study, which was the only pivotal study proving the benefit of adjuvant chemotherapy in these patients. Long-term survival data from CLASSIC are awaited with interest.boxed-text

A randomized phase II trial of S-1-oxaliplatin versus capecitabine–oxaliplatin in advanced gastric cancer

PurposeS-1 or capecitabine plus oxaliplatin are considered active and tolerable in gastric cancer patients. We conducted a randomized phase II trial in gastric cancer patients to compare the activity and safety of these combinations. MethodsThe patients received S-1 at 80mg/m2 for 14days, followed by a 7-day rest period within a 3-week schedule in the S-1/oxaliplatin (SOX) arm, and capecitabine at 2000mg/m2 for 14days, followed by a 7-day rest period within a 3-week schedule in the capecitabine/oxaliplatin (CAPOX) arm. Oxaliplatin 130mg/m2 was administered every 3weeks in both arms. ResultsOne hundred twenty-nine patients were randomly assigned to SOX (N=65) or CAPOX (N=64). The median time to progression and the overall survival were 6.2 and 12.4months with SOX, respectively; and 7.2 and 13.3months with CAPOX, respectively. The overall response rates were 40% and 44% for SOX and CAPOX, respectively. The most frequent grade 3 or 4 toxicities were thrombocytopenia (15.4%) for SOX and neutropenia (18.8%) for CAPOX. The median time to 10% deteriorations in global health scores was similar in both arms (SOX, 4.3months, CAPOX, 4.9months). ConclusionBoth the SOX and CAPOX regimens were equally active and well tolerated in advanced gastric cancer patients.

A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection

BackgroundPerioperative chemotherapy improves outcome in resectable colorectal liver-only metastasis (CLM). This study aimed to evaluate perioperative CAPOX (capecitabine–oxaliplatin) plus bevacizumab in patients with poor-risk CLM not selected for upfront resection. Patients and methodsPoor-risk CLM was defined as follows: more than four metastases, diameter >5 cm, R0 resection unlikely, inadequate viable liver function if undergoing upfront resection, inability to retain liver vascular supply, or synchronous colorectal primary presentation. Patients underwent baseline computed tomography, magnetic resonance imaging, and/or positron emission tomography (PET) for staging and received neoadjuvant CAPOX plus bevacizumab, with resectability assessed every four cycles. Primary end point was radiological objective response rate (ORR). ResultsForty-six patients were recruited, of which 91% underwent PET to ensure metastases confined to liver. Following neoadjuvant CAPOX plus bevacizumab, the ORR was 78% (95% confidence interval 63% to 89%). This allowed 12 of 30 (40%) patients with initial nonsynchronous unresectable CLM to be converted to resectability. In addition, 10 of 15 (67%) patients with synchronous resectable CLM underwent liver resection, with four additional patients being observed alone due to excellent response to neoadjuvant therapy. No grade 3–4 perioperative complications were seen. ConclusionNeoadjuvant CAPOX plus bevacizumab resulted in a high response rate for patients with CLMs with poor-risk features not selected for upfront resection and converted 40% of patients to resectability.

Systemic therapy for advanced gastric cancer: a clinical practice guideline.

What is the optimal chemotherapy regimen in advanced gastric cancer? Gastric cancer is the second leading cause of cancer mortality worldwide. Despite low incidence rates for gastric cancer in Ontario, the overall prognosis is bleak, with 5-year survival rates of approximately 23% in Canada. Even with the considerable body of research available on chemotherapy for advanced gastric cancer, uncertainty remains. There is no recognized standard treatment, and there appears to be geographic variation in practice. Outcomes of interest were overall survival, objective response rate (complete plus partial responses), time to disease progression, adverse effects, and quality of life. After a systematic review, a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted. The practice guideline was reviewed and approved by the Gastrointestinal Disease Site Group (gi dsg) and the Report Approval Panel of the Program in Evidence-Based Care. External review by Ontario practitioners was obtained through a survey, the results of which were incorporated into the practice guideline. The gi dsg makes the following recommendations: To improve survival, a platinum agent should be included in any combination chemotherapy regimen.Within a combination chemotherapy regimen, oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is, epirubicin-cisplatin-capecitabine is preferred over the prior standard regimen, epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine (eox) is a reasonable alternative to ecf. The choice between ecf and eox should be based on patient preference.Trastuzumab in combination with cisplatin and a fluoropyrimidine (5fu or oral capecitabine) is recommended for advanced gastric cancer positive for the human epidermal growth factor receptor 2 (her2/neu).

Effectiveness of I and II line chemo-targeted therapy according to the scheme Oxaliplatin Capecitabine Bevacizumab (XELOX BVZ) in patients with metastatic colorectal cancer (mCRC)

Effectiveness of I and II line chemo-targeted therapy according to the scheme Oxaliplatin Capecitabine Bevacizumab (XELOX BVZ) in patients with metastatic colorectal cancer (mCRC)

A randomized phase III study of sox (S-1/oxaliplatin) versus COX (capecitabine/oxaliplatin) in patients with advanced colorectal cancer.

3524 Background: A regimen consisting of capecitabine and oxaliplatin (COX) is widely used in Korea in the first-line treatment of metastatic colorectal cancer (MCRC). S-1 may have considerable activity compared with capecitabine. Phase I and II studies showed that S-1 plus oxaliplatin (SOX) might have at least comparable activity with COX in MCRC. The aim of study was to evaluate whether SOX is noninferior to COX in terms of progression free survival (PFS) in patients previously untreated with systemic therapy for MCRC. Our hypothesis was that SOX is non-inferior to COX if the upper limit of 95% confidence interval for hazard ratio (HZ) between those two arms is below 1.4327, which comes from the non-inferiority margin of 13% in progress-free survival at 15 months. Methods: This study was a randomized, two-arm, non-inferiority, phase III comparison of SOX versus COX. Patients with MCRC were stratified according to primary site (colon vs. rectum), previous treatment (adjuvant therapy vs. none) and status ...

Three-year outcomes of GCR-3: A phase II randomized trial comparing conventional preoperative chemoradiation (CRT) followed by surgery and postoperative adjuvant chemotherapy (CT) with induction CT followed by CRT and surgery in locally advanced rectal cancer.

3552 Background: Compared with postoperative adjuvant Capecitabine/Oxaliplatin (CAPOX), induction chemotherapy before to CRT had similar pCR rates, but did achieve more favourable compliance and toxicity profiles as we previously have published. (J Clin Oncol 28:859-865, 2010). We now report on the 3-year outcomes of this randomized trial. Methods: Patients with locally advanced rectal cancer and stratified by institution, were randomly assigned to arm A—preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant CAPOX—or arm B—induction CAPOX followed by CRT and surgery. The following three-year outcomes were assessed: the cumulative incidence of local-regional (LRF) and distance failure (DF), disease-free (DFS) and overall (OS) using the Kaplan-Meier method. Results: Of 108 patients accrued, 103 were analyzable for outcomes. With a median follow-up time of 39.3 months (0.1-53), the 36 DFS rates were 68% (95% CI, 53% to 80%) for arm A and 70% (95% CI, 55% to 80%) in arm B. (p=0.97). The 36-month overall survival rates were 90% (95% CI, 77% to 96%) and 81%(95% CI, 68%to 89%) for arms A and B, respectively (p= 0.18). 11 patients experienced relapse in arm A (1 local, 10 distant),and 12 experienced relapse in arm B (2 local, and 10 distant). p = 0.6036. Conclusions: Although not powered to draw any comparative conclusions, induction CT prior to CRT and surgery for the treatment of locally advanced rectal cancer yields similar three-year outcomes as standard strategy. Because of the associated acute toxicity sparing and better compliance, a larger trial is warranted with this strategy.