Dose Intensity Of Oxaliplatin Research Articles

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis

BackgroundColorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists.MethodsPatients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined.ResultsFive hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08–0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33–0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33–0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38–1.02, p = 0.06).ConclusionsIn resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Splenomegaly during oxaliplatin-based chemotherapy: impact on blood parameters and anti-neoplastic treatment

BackgroundOxaliplatin induces splenomegaly, which can cause blood sequestration and relevant cytopenia, leading to further dose reductions and schedule modifications of chemotherapy. Here, we aimed to explore the changes of spleen volume induced by oxaliplatin as well as its impact on blood parameters and anti-neoplastic treatment in patients with colon cancer.MethodsWe conducted a retrospective analysis of patients with resectable stage II–IV colon cancer who were treated with oxaliplatin and capecitabine at our institution from January 2016 to December 2017. Laboratory tests and computed tomographic (CT) data before, during and up to 18 months after the end of chemotherapy were extracted. Spleen volume was determined by volumetric measurements. Splenomegaly was defined as an over 30% increase in spleen volume from baseline.ResultsOut of 144 patients, 102 patients (70.8%) developed splenomegaly, and 75 (73.5%) recovered at 18 months after the end of chemotherapy. Higher cumulative dose intensity of oxaliplatin (P=0.001) and higher baseline platelet count (P=0.045) were risk factors associated with splenomegaly. Compared to those without splenomegaly, splenomegaly patients experienced more severe reduction in platelet (P<0.001), erythrocyte (P=0.010), neutrophil (P=0.002) and lymphocyte (P=0.006) counts and were more likely to undergo dose reductions of oxaliplatin (21.6% vs. 7.1%, P=0.038) as well as interruptions of chemotherapy (18.6% vs. 4.8%, P=0.040) due to thrombocytopenia.ConclusionsSplenomegaly was a common and partly irreversible side effect of oxaliplatin-based therapy in patients with colon cancer. It is correlated with more severe pancytopenia and might exert a negative impact on the efficacy of anti-neoplastic treatment.

Survival and Predictive Factors of Chemotherapy With FOLFIRINOX as First-Line Therapy in Metastatic Pancreatic Cancer: A Retrospective Multicentric Analysis.

The use of FOLFIRINOX (a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) is one of the therapeutic standards in pancreatic adenocarcinoma. We analyzed progression-free survival (PFS) and overall survival (OS) and their predictive factors in patients treated with FOLFIRINOX as first-line therapy in metastatic pancreatic cancer. This multicenter retrospective analysis included patients treated with FOLFIRINOX between 2011 and 2015. The Kaplan-Meier method was used to estimate OS and PFS. The statistical comparison for survival was performed by the log-rank test. Predictive factors were estimated in multivariate analysis with the use of a Cox model. One hundred and thirty-six patients were included (74 men, 62 women; median age, 62 years [range, 29-74 years]). The median PFS was 5.97 months (95% confidence interval, 4.4-6.63 months). The median OS was 8.93 months (95% confidence interval, 7.4-10.07 months). Prognostic factors in multivariate analysis were the use of granulocyte colony-stimulating factor, which appeared to be a good prognostic factor. Dose intensity of oxaliplatin (≥74.48%) and dose intensity of bolus of fluorouracil (>6.9%) appeared as pejorative factors. In patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX in first line, dose modifications at the onset of adverse effects and early use of granulocyte-colony stimulating factor seem to be associated with a better survival.

Clinical efficacy and safety of early adjuvant chemotherapy for stage III colon cancer: Short-term outcomes of a multicenter, randomized, open-label, phase 3 trial.

3598 Background: Adjuvant chemotherapy (AC) is recommended to commence within 8 weeks since after surgical resection of stage II or III colon cancer. Results of many retrospective studies showed inferior survival outcomes following delay of AC delay. Moreover, preclinical studies showed that the progression of disseminated cancer cells is profound during the postoperative period. This study is the first prospective trial to evaluate early (≤ 14 days postoperative) AC for patients (pts) with stage III colon cancer. Methods: This study is a prospective, multicenter, randomized phase III trial. Pts with pathological stage III colon cancer were enrolled and randomized 1:1 to early AC (starting AC ≤ 14 days after surgery) or conventional AC (starting AC &gt; 14 days after surgery). Pts were recommended to receive 12 cycles of FOLFOX-6 for AC. The primary endpoint was disease-free survival. The secondary endpoints were overall survival, adverse events, surgical complication during AC, and patient-reported outcomes (quality of life) during 1 year after surgery. Herein, safety data, chemotherapy delivery, and quality of life are presented. Results: This study randomized 443 pts either early AC arm (221pts) or early AC arm (222 pts) to the during September 2011 to March 2020. 380 pts who received at least one cycle of FOLFOX-6 were included in the safety analysis (192 and 188 in the early and conventional AC arms, respectively). The baseline characteristics of the two groups were well-balanced except for the interval from the surgery to the initial AC. The early and conventional AC arms started their first chemotherapy at median of 13 (4-43 days) and 29 (17-53 days) after surgery (p &lt; 0.001), respectively. No significant differences were seen in the median chemotherapy cycles, AC completion, and relative oxaliplatin dose intensity between groups. AC Completion without any change of dose or schedule delay was seen in 18% and 20% in early and conventional AC arms respectively, while dose reduction or delay was 65% and 61%, respectively. Toxicities of grade 3 or more were seen in 28% in both groups. One patient in the early AC arm underwent an emergent operation for anastomotic leakage on the second day of 5-fluorouracil infusion (postoperative day 14). However, the surgical complication was not seen in any other patient. The scores of the European Organization for Research and Treatment of Cancer Quality of Life core 30 questionnaire were similar in both arms at baseline (before starting AC), and 1 month, 3 months, 6 months, and 12 months after surgery. Conclusions: Early AC was safe and did not increase either chemotherapy-related adverse events or surgery-related complications during treatment. Moreover early AC did not reduce the quality of life of the pts during 1 year after surgery. This study continues to follow-up the patients for survival outcomes. Clinical trial information: NCT01460589.

Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study

BackgroundOxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients.MethodsThe study included 365 patients treated at five oncology centers in Poland between 2000 and 2014. Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the α level of 0.05 was employed.ResultsThe median follow-up was 51.8 months (range 8.2–115.1). Early recurrence < 36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt < 60% of RDI-O was associated with early recurrence within 18 months after surgery (OR = 2.05; 95%CI: 1.18–3.51; p = 0.010), especially in low-risk group (HR = 1.56 (95%CI: 0.96–2.53), p = 0.07). In the multivariate analysis early recurrence was correlated with grade (OR = 2.47; 95% CI: 1.25–4.8; p = 0.008), pN (OR = 2.63; 95% CI: 1.55–4.54; p < 0.001), the number of lymph nodes harvested (OR = 0.51; 95% CI: 0.29–0.86; p = 0.013) and RDI-O (OR = 1.91; 95%CI: 1.06–3.39; p = 0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR = 22.9 (95%CI: 13.9–37.6; p < 0.001).ConclusionsRDI-O < 60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

BackgroundThere is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival.MethodsFrom 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion).ResultsIn total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively.ConclusionsThe mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: A multicenter retrospective analysis.

248 Background: Colorectal cancer remains the second leading cause of cancer death in developed countries. The benefit of using fluorouracil-based chemotherapy with oxaliplatin, such as FOLFOX (fluorouracil (5-FU), leucovorin, oxaliplatin) and CAPOX (capecitabine and oxaliplatin) is well established. The optimal dose intensity (DI) under which overall survival (OS) is inferior is not established. Methods: Patients (pts) treated with adjuvant chemotherapy between 2006 and 2011 for resected stage III colon cancer (CC) from four academic cancer centres in Canada were retrospectively analysed. Patients that received CAPOX and FOLFOX were examined for the relationship between DI and OS. Results: A total of 625 pts with resected high risk stage II or stage III CC that received adjuvant chemotherapy were analysed. The median age was 63. Pts with T4 and N2 disease comprised 35.4% and 29.9% of pts, respectively. Median follow-up was 3.2 years. There was available survival data for 319 pts. The median oxaliplatin DI was 70%. The frequency of pts reaching an oxaliplatin DI of &gt; 80% was 43%, while 76.6% of pts had a dose intensity of &gt; 80% for their FU component. An oxaliplatin DI of &gt; 80% was associated with a significant improvement in survival, HR = 0.42 (95%CI 0.21 – 0.81, p &lt; 0.01). Achieving a DI of &gt; 80% for capecitabine or 5-FU did not improve OS. Other factors associated with inferior OS included T4 (HR = 3.5, p = 0.03) and N2 (HR = 5.27, p = 0.0005) subgroups. The improvement in OS was not significant when restricting the analysis to pts with non-T4 and non-N2 disease (n = 144), HR = 0.16 (0.02 – 1.26; p = 0.08). Conclusions: Oxaliplatin DI of &gt; 80% is associated with improved OS in patients receiving chemotherapy for high risk stage II and stage III CC.

Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx) in Refractory/Relapsed (R/R) DLBCL. a Real Life Study in Patients Ineligible for Autologous Transplantation

Introduction: There is no standard treatment of refractory or relapsed (R/R) patients (pts) with DLBCL ineligible for autologous stem-cell transplantation (ASCT). However, R-GemOx is widely used in these circumstances. We here report the results of a retrospective analysis of a cohort of patient treated in two academic centers in France. The main objectives were to evaluate the activity and safety profile of this regimen in a large series of R/R DLBCL pts in a real life setting. Methods: Patients selected had to have de novo or transformed DLBCL, R/R after at least one line of treatment containing doxorubicin and rituximab, to be ineligible for ASCT and to have received at least one cycle of R-GEMOX. Rituximab 375 mg/m2 was administered on D1, gemcitabine 1000 mg/m2 on D2 and oxaliplatin 100 mg/m2 on D2 as previously described (Mounier N. et al. Haematologica 2013; 98:1726-31). Cycles were given every 2 weeks and 8 cycles were planned if at least a partial response (PR) was obtained after 4 cycles. Results: Between May 2002 and May 2017, 196 pts were treated. Baseline characteristics were: median age: 72 y (range, 24-89), international prognostic index (IPI) 3-5: 63%, refractory state to last treatment (tx): 42%, history of indolent lymphoma: 45%, prior ASCT: 16%. The median number of previous line was 1 (range 1-7) with 112 pts having received R-GemOx in second line. One hundred and thirty-six pts received at least 4 cycles, 86 pts completed 6 cycles and 61 pts 8 cycles. After 4 cycles, the overall response rate (ORR) according to IWC (Cheson 1999 or 2007) was 54 % and the complete response (CR) rate was 23 %. At the end of treatment, the ORR and CR rates were 38 % and 33 %, respectively. With a median follow-up of 22 months, median (m) progression-free survival (PFS) and overall survival (OS) were 5 and 10 months (mo), respectively. mOS was significantly longer in case of prior history of indolent lymphoma (21 vs 8 mo, p &lt; 0.001), age&lt;75y (16 v 7mo, p &lt; 0.001), IPI &lt;3 (p &lt; 0.001), non-refractory status to last treatment (18 v 7mo, p &lt; 0.001). The mOS of patients who attained a CR was 40 mo. Among pts who were treated with R-GemOx in second line, the CR rate was similar (32%), the same factors influenced the OS and duration of a first remission longer than 12 months was a favorable factor (p=0.006). Based on data collected from the population who received the first four cycles, (136 patients and 848 cycles) the median received dose intensities of oxaliplatin and gemcitabine were 73.1 %, and 75.8% of the theoretical dose, respectively. The most common toxicities during treatment were hematological and manageable. Grade 3-4 toxicities occurred in 30.6% of pts. Grade 1-2 peripheral neuropathy related to oxaliplatin was observed in 26% of the patients, with only 2 patients presenting a grade 3 peripheral neuropathy. Summary/Conclusion: This real life study of R/R DLBCL, confirms the activity and safety of R-GemOx. This combination represents a platform to be combined with targeted therapies as it is currently proposed with nivolumab in the phase 3 NIVEAU trial (NCT03366272) and planned with polatuzumab vedotin (POLARGO trial). However, facing this very high unmet medical need, new approaches including CAR T-cells should also be considered in this patient population. Disclosures Belhadj: Janssen: Honoraria; Celgene: Honoraria, Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work; Takeda: Honoraria; Amgen: Honoraria. Le Bras:Pfizer: Other: Travel grant; Takeda: Research Funding; Jansen: Other: Travel grant. Jardin:amgen: Honoraria; Servier: Honoraria; celgene: Honoraria; roche: Honoraria; janssen: Honoraria. Tilly:Roche: Consultancy; Celgene: Consultancy, Research Funding; Astra-Zeneca: Consultancy; Karyopharm: Consultancy; BMS: Honoraria; Janssen: Honoraria; Gilead: Honoraria; merck: Honoraria; servier: Honoraria; roche: Membership on an entity's Board of Directors or advisory committees. Haioun:F. Hoffmann-La Roche Ltd: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Servier: Honoraria; Miltenyi: Honoraria; Takeda: Honoraria.

573P - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)

BackgroundThe aim of this study was to evaluate the efficacy and safety of CAPOX with planned oxaliplatin stop-and-go strategy compared to continuous use of oxaliplatin as an adjuvant setting for colon cancer. MethodsPatients with curative resection of colon cancerwere randomly assigned to receive eitherCAPOX with continuous use of oxaliplatin (8 cycles of CAPOX; continuous arm) or CAPOX intermittentuse of oxaliplatin (2 cycles of CAPOX – 4 cycles of capecitabine – 2 cycles of CAPOX; intermittentarm).The primary endpoints were frequency of peripheral sensory neuropathy (PSN) at 1-year after surgery and disease-free survival rate at 3-year after surgery. The secondary end points included overall survival (OS), compliance and safety. ResultsA total of 200 patients were enrolled. The intent-to-treat and safety population comprised 100 and 99 patients in the continuous arm,and 100 and 98 patients in the intermittentarm. Compliance: The overall treatment completion rate and relative dose intensity of oxaliplatin were 64% and 71% in the continuous arm vs.92% and 95% in the intermittentarm(p=0.21 and 0.12, respectively). Efficacy: The 3-year DFS was 81.6% in the continuous arm vs.82.4% in the intermittentarm(HR, 0.82; 95% CI, 0.48-1.18). Safety: The incidence of PSN (>grade 2) was 33%in the continuous arm vs.15% in the intermittentarm (p<0.001). The frequencies ofPSF lasting for 1-year and 3-year were 61% and 30% vs. 21% and 6%, respectively. ConclusionsCAPOX withplanned oxaliplatin stop-and-go strategy could be equally effectiveas an adjuvant setting for colon cancer, and substantially reduce long-term PSN and potential improve patient quality of life. Clinical trial identification000012535 (09/December/2013). Legal entity responsible for the studyYasuhiro Kodera (Chubu Clinical Oncology Group, Japan). FundingChubu Clinical Oncology Group. DisclosureAll authors have declared no conflicts of interest.

Nutritional status predicts adjuvant chemotherapy outcomes for stage III colorectal cancer.

Objectives: Previously, adjuvant chemotherapy using oxaliplatin was a standard treatment for patients with node-positive colorectal cancer (CRC) who underwent curative surgery. The factor predicting adverse events and therapeutic effect have not yet been established. Methods: A retrospective cohort of 42 patients diagnosed with stage III CRC between April 2009 and March 2013 in our institution were included in this study. The indicators of host nutritional status were body weight (BW), body mass index (BMI), serum albumin, Onodera's prognostic nutritional index (OPNI), and Glasgow Prognostic Score (GPS). The indicators of host immunocompetence was total lymphocyte counts, total neutrophil counts, granulocytes/lymphocytes ratio (G/L ratio). Results: The overall recurrence rate was 26.1%. Patients who had a recurrence were more likely to be older. The recurrence was not associated with type of regimen or adverse events. The cases with a few cumulative doses and relative dose intensity of oxaliplatin experienced significantly more recurrence. Nutritional status indicators, such as the serum albumin level, OPNI, and the modified Glasgow prognostic score (mGPS) were associated with the adjuvant chemotherapy outcome. Our study results indicated worse nutritional status induced worse disease-free survival (DFS) and more recurrence. Conclusion: The host's nutritional status associated with outcomes in stage III CRC patients.

P-223 - NORTH/HGCSG1003: A phase II study evaluating the safety and efficacy of FOLFOX as adjuvant chemotherapy for patients with stage III colon cancer: Comparison with medical oncologists and surgeons

Introduction: The efficacy of oxaliplatin containing regimens were confirmed in large randomized phase III trials in which they were superior to fluorouracil and leucovorin as adjuvant setting for patients with stage III colon cancer. In Japan, not only medical oncologists but also surgeons practice chemotherapy. In this analysis, we investigated differences in safety and efficacy between surgeons and medical oncologists from NORTH/HGCSG1003 study. Methods: NORTH/HGCSG1003 is a multicenter phase II study. This study enrolled patients with resected stage III colon cancer. Patients received FOLFOX4 or mFOLFOX6 repeated every 2 weeks for 12 cycles. Primary endpoint is disease-free survival, and secondary endpoints were overall survival, safety, RDI and so on. In this analysis, pts characteristics and safety were compared using Fisher’s exact test. Dose intensity was compared using Student's t-test, and DFS and RFS using log-rank test. Results: From September 2010 to March 2013, 273 patients at 28 institutions were enrolled. In the eligible population (n = 264), 159 patients were treated with chemotherapy by medical oncologists (group O) and 105 patients by surgeons (group S). Patients’ characteristics between two groups were well balanced except for bowel obstruction before surgery (8.8% in group O vs 23.8% in group S; p = 0.001). Median RDI (group O vs group S) of oxaliplatin was 0.631 vs 0.751 (p Conclusion: RDI of oxaliplatin and bolus 5-FU were significantly lower in group O than group S. The frequency of platelet count decreased (all grade) was significantly less in O. This was presumed to be because the relative dose intensity of oxaliplatin was significantly lower in O. However, there was no significant difference in the frequency of peripheral sensory neuropathy. There was no significant difference in efficacy between O and S.

Retrospective comparison of modified FOLFIRINOX with full-dose FOLFIRINOX for advanced pancreatic cancer: A Japanese cancer center experience.

469 Background: Various modified FOLFIRINOX (mFFX) regimens have been reported and widely used in clinical practice. Although there are retrospective studies and single-arm phase 2 studies comparing modified regimens to the full-dose regimen of the historical control group, head-to-head comparisons in the same population are limited. This study aimed to compare mFFX with full-dose FOLFIRINOX (fFFX) in patients with advanced pancreatic cancer (APC). Methods: We reviewed 85 patients with APC who received mFFX (no bolus fluorouracil and irinotecan 150 mg per square) or fFFX as first-line chemotherapy between January 2014 and December 2016. mFFX has been used since January 2016 on the basis of results of a Japanese phase 2 study. The efficacy, safety, and dose reduction pattern were evaluated. Results: A total of 56 eligible patients (26 treated with mFFX and 30 with fFFX) were selected. Baseline characteristics of each group were well-balanced. The median relative dose intensities of oxaliplatin, irinotecan, bolus fluorouracil, and continuous infusion fluorouracil were 68.6%, 78.5%, 0%, and 88.5% in the mFFX group, and 80.5%, 76.5%, 25.6%, and 83.6% in the fFFX group, respectively. Second cycle dose reduction occurred in 38% of the patients in the mFFX group and in 62% of those in the fFFX group. The median overall survival (OS) was 19.0 months in the mFFX group, compared to 13.2 months in the fFFX group (HR 0.60, 95% CI 0.25–1.47, P = 0.27). In a multivariate analysis to adjust for prognostic factors for OS, the hazard ratio for death with mFFX was significant (adjusted HR 0.36, 95% CI 0.14–0.93, P = 0.04). The median progression-free survival was 8.3 months in the mFFX group and 5.9 months in the fFFX group (HR 0.83, 95% CI 0.44–1.54, P = 0.55). The response rate was 35% in the mFFX group versus 30% (P = 0.78) in the fFFX group, respectively. Grade 3 or 4 leucopenia (15% versus 40%), neutropenia (42% versus 70%), febrile neutropenia (8% versus 17%), and nausea (4% versus 13%) were decreased in the mFFX group, but the differences were not statistically significant. Conclusions: mFFX had equivalent or higher efficacy and improved safety compared to fFFX in the same population.

Oxaliplatin/5-fluorouracil-based adjuvant chemotherapy as a standard of care for colon cancer in clinical practice: Outcomes of the ACCElox registry.

The ACCElox registry was set up to assess therapeutic management of early-stage colon cancer with oxaliplatin/5-fluorouracil (5-FU)-based regimen and the duration of adjuvant chemotherapy in current clinical practice. This prospective observational study was conducted between 2006 and 2008 in 19 countries on 1548 newly diagnosed patients with stage II/III colon cancer, who had complete resection of the primary tumor and treated with at least one dose of oxaliplatin. The patient/disease characteristics, dose intensity, toxicity management, treatment delay and duration of disease-free survival (DFS)/relapse were assessed. About 73 and 27% of the patients were diagnosed with stage III (Dukes C) and stage II (Dukes B2) colon cancer, respectively. Overall, 74.4% patients completed the prescribed chemotherapy (FOLFOX 88%) and 97.6% patients received at least two cycles of oxaliplatin chemotherapy. The median actual dose intensity of oxaliplatin per cycle was 85 mg/m(2) . Relapse within 3 years occurred in 18.4% of patients with similar rate in all three groups (FOLFOX - 18.1%, FLOX - 19%, XELOX - 18.6%). At 3 years follow-up only 72 deaths were reported. The most common adverse events (AEs) at any cycle were neutropenia (63.9%), thrombocytopenia (23.3%), diarrhea (9.7%), sensory neuropathy (4.5%) and infection (2.6%). Disorders of central and peripheral nervous systems were frequently reported AEs at 6 months (54.3%, grade ≥1) and 12 months (36.4%, grade ≥1) of follow-up. Majority of the patients completed the prescribed oxaliplatin/5-FU regimen. There was no significant difference in the DFS among these regimens. Our results confirm the favorable benefit/risk profile of oxaliplatin/5-FU-based regimens in this setting in clinical practice.

High Risk Stage 2 and Stage 3 Colon Cancer, Predictors of Recurrence and Effect of Adjuvant Therapy in a Nonselected Population.

Patients with stage 2 and stage 3 colon cancer often are treated with adjuvant chemotherapy. However, patients seen in daily practice have more comorbidity than those enrolled in clinical trials. This study aims to evaluate prognostic factors for recurrence and to ascertain the benefit of adjuvant chemotherapy on recurrence-free survival (RFS) of patients in a nonselected population. Furthermore, the impact of relative dose intensity (RDI) of adjuvant therapy on RFS is examined. Chart review was performed for 243 consecutive patients diagnosed and treated at a single center for stage 2 and stage 3 colon cancer from 2002 to 2008. Adjuvant chemotherapy was administered to 66 patients. Median overall survival (OS) was 5.84 years and median RFS was 5.37 years. For stage 2 disease, patients treated with or without adjuvant therapy had a median RFS of 5.49 and 5.73, respectively (p = ns). For stage 3 disease, median RFS rates were 5.08 and 1.19, respectively (p = 0.084). Overall RDI of oxaliplatin based chemotherapy higher than median was associated with increased RFS (p = 0.045). In conclusion, adjuvant therapy did not significantly increase recurrence-free survival. This could be the result of comorbidity in patients. Relative dose intensity of oxaliplatin based therapy is associated with RFS.

A multi-institutional feasibility study of S-1/oxaliplatin (SOX) plus bevacizumab in patients with advanced/metastatic colorectal cancer: HiSCO-02 prospective phase II study.

728 Background: mFOLFOX6 regimen, which is a standard regimen for metastatic colorectal cancer (CRC), is inconvenient owing to its requirement for continuous infusion via vascular access. We aimed to investigate the efficacy and safety of S-1/oxaliplatin (SOX) plus bevacizumab, a promising alternative treatment to replace mFOLFOX6. Methods: We undertook a clinical phase II trial in 12 institutions in Hiroshima, Japan. We enrolled individuals aged 20–80 years who had metastatic CRC, had an Eastern Cooperative Oncology Group performance status (PS) of 0 or 1, had assessable lesions, and had received no previous chemotherapy. Eligible patients were assigned SOX plus bevacizumab (S-1: 80-120 mg/body/day, day 1–14 orally administrated, oxaliplatin: 130mg/m2 day 1 i.v., bevacizumab: 7.5mg/kg day 1 i.v. q3w). The primary endpoint was response rate (RR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Results: From May 2011 to January 2014, 55 patients (mean age, 64 years) were enrolled. The number of metastatic organs were one: 29 cases (52.7%), two or more: 25 cases (45.4%), and 2 cases had no target lesions (3.6%). Median follow up time was 12.8 months (range, 1.4-38.6 months). RR was 45.4% (95% CI, 32.2%-58.6%) and disease control rate was 87.3% (95% CI, 78.5-96.1%). Median PFS and OS time were 9.2 months (95% CI, 7.6-10.8) and 22.0 months (95% CI, 17.7-26.2), respectively. The median number of cycles of chemotherapy was 7 (range, 1-16). The median relative dose intensity of oxaliplatin, S-1, and bevacizumab were 85%, 85%, and 87%, respectively. Major toxic effects (grade 3/4) were thrombocytopenia (5.7%), neutropenia (7.5%), sensory neuropathy (13.2%), and anorexia (17.0%). Conclusions: These data indicated that the SOX plus bevacizumab regimen is effective and well tolerated in patients with metastatic CRC. Clinical trial information: UMIN000004976.

Neutropenia and relative dose intensity on adjuvant FOLFOX chemotherapy are not associated with survival for resected colon cancer.

Adjuvant folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy for resected high-risk colon cancer is associated with a low risk of febrile neutropenia (FN). Neutropenia, however, is a common cause of dose modification or delay with unknown consequences on outcomes. We examined the effect of neutropenia-related and other dose-limiting toxicities and relative dose intensity of oxaliplatin and 5-FU, on relapse-free and overall survival in patients treated with FOLFOX chemotherapy for resected high-risk colon cancer. A chart review was conducted on patients treated at the British Columbia Cancer Agency receiving ≥1cycle of mFOLFOX6 chemotherapy for resected stage II or III colon cancer between January 1, 2006, and December 31, 2007. Relapse-free survival (RFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. One hundred fourteen patients (median age 59years, 44% male, 98% stage III, median follow-up 5.2years) were included. Ninety percent of the patients experienced any dose-limiting toxicity (DLT), while 58% of the patients had a neutropenia-related DLT. There were no documented episodes of FN. Granulocyte colony-stimulating factor (GCSF) was used in 10% of the patients. Median relative dose intensity (RDI) was 81 and 85% for oxaliplatin and 5-FU, respectively. Oxaliplatin and 5-FU RDI were not associated with RFS or OS when analyzed as continuous variables or categorically. Grade II or grade III/IV neutropenia compared to no neutropenia was not associated with RFS or OS. DLTs affect the majority of patients on adjuvant FOLFOX for high-risk colon cancer, but RFS and OS do not appear to be affected by the associated lower RDI of oxaliplatin and 5-FU.

Locally advanced or metastatic pancreatic cancer in elderly patients: Chemotherapy versus best supportive care

(60.4%) patients received 5-fluorouracil-based adjuvant chemotherapy (30 (46.9%)≥ 75 years old versus 34 (53.1%) b 75 years old). Older patients had similar clinico-pathological characteristics as younger patients. The median follow-up duration was 14.9 months. The 3-year disease-free survival (26.4%≥ 75 years old versus 40% b 75 years old, P = 0.006) was different. Elderly patient received a lower relative dose intensity of Oxaliplatin and 5-fluorouracil (57.7 versus 64.4 (P = 0.418)). Conclusion: Adjuvant fluorouracil-based chemotherapy result in different efficacy without in older patient age ≥ 75 years when compared with best younger patients with curatively resected stage II,III colon cancer. Therefore, for colon cancer patients aged ≥75 years can be recommended to receive a lower relative dose intensity of 5-fluorouracil after curative surgery in Korea. Disclosure of interest: None declared.

Practical Outcome of Adjuvant FOLFOX4 Chemotherapy in Elderly Patients with Stage III Colon Cancer: Single-center Study in Korea

Elderly patients derive similar benefits from 5-fluorouracil-based adjuvant chemotherapy in Stage III colon cancer; however, conflicting data exist regarding additional benefit from oxaliplatin, fluorouracil and leucovorin (FOLFOX) chemotherapy. Single-center, retrospective analysis was performed to compare the safety and efficacy of adjuvant oxaliplatin, fluorouracil and leucovorin-4 chemotherapy in older patients (age ≥65 years) with younger patients with Stage III colon cancer after surgical resection. Among 391 patients with Stage III colon cancer, 229 patients received adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy (87 (43.5%) ≥65 years old versus 142 (74.3%) <65 years old). Older patients had similar clinico-pathological characteristics as younger patients except for higher Charlson-Age comorbidity score (median 3.44 versus 2.85, P < 0.01). The estimated 3-year disease-free survival (76.5 versus 80.0%, P = 0.88) and 3-year overall survival (90.9 versus 92.7%, P = 0.98) were similar. Grade 3-4 neutropenia was the only toxicity with higher frequency in the elderly patients (62.1 versus 46.5%, P = 0.02). Elderly patients received a lower relative dose intensity of oxaliplatin (0.76 versus 0.79) and 5-fluorouracil (0.75 versus 0.80, P = 0.009). Adjuvant oxaliplatin, fluorouracil and leucovorin chemotherapy resulted in similar efficacy without significant increase in toxicity in older patients aged ≥65 when compared with younger patients with curatively resected Stage III colon cancer. Therefore, for colon cancer patients aged ≥65, oxaliplatin, fluorouracil and leucovorin chemotherapy can be recommended as safe and effective adjuvant chemotherapy after curative surgery in Asia.

620 - Impact of the Interval Between Surgery and Adjuvant MFOLFOX6 on Survival of Colon Cancer Patients

ABSTRACT Background Adjuvant chemotherapy with the association of Oxaliplatin and Fluoropyrimidines has shown to reduce recurrence risk and improve survival in stage III colon cancer patients in comparison to Fluoropyrimidines alone. The ideal timing for the start of adjuvant chemotherapy has not been defined. Our aim was to determine the impact of the interval between surgery and the start of adjuvant chemotherapy on survival of colon cancer patients. Material and methods Retrospective cohort study, in a Portuguese cancer centre, of colon cancer (CC) patients treated with mFOLFOX6 in the adjuvant setting, from September 2004 till November 2009. Two groups of patients were defined according to the timing of adjuvant chemotherapy (CT): ≤ 8weeks or >8 weeks after surgery. Efficacy was evaluated by overall survival (OS) and disease-free survival (DFS). Hazard ratios and 95% confidence intervals were calculated with the use of the Cox proportional hazards model. Results Two hundred and seventy seven patients were treated with adjuvant mFOLFOX6 and followed for a median time of 45 months. Median age was 62 years (28-79); 57% were male and 77% had stage III CC. Median time to the start of CT was 8 weeks (P25 = 7, P75 = 10). The group of patients that started CT > 8 weeks after surgery was older (mean age: 62 vs 59 years, p = 0.001) and tended to accomplish lower relative dose-intensity of Oxaliplatin and 5-Fluorouracil (69,5% vs 72% and 73% vs 76%, respectively; p > 0.05). There was a tendency to lower OS and DFS in the group that started CT >8 weeks after surgery. At 3 years, the probability of OS was 83% vs 90% (p = 0.118), and DFS: 75% vs 77% (p = 0.751). Multivariate analysis showed that the interval between surgery and the start of adjuvant CT had no impact in OS nor DFS. Conclusions Our data point to a tendency to better survival when CT is started within 8 weeks of surgery, strengthening the need for a timely referral of patients to adjuvant treatment. The small sample size and the short follow-up might explain why we were unable to find statistical significance in this association. Disclosure All authors have declared no conflicts of interest.

591P - Colon Cancer Adjuvant Mfolfox-6 – Survival Impact of Oxaliplatin Reduced Dose-Intensity

ABSTRACT Background Adjuvant colon cancer treatment may include the oxaliplatin/fluoropirimidine combination. This association has shown benefit on progression free survival (PFS) and overall survival (OS) compared to fluoropirimidine monotherapy in these patients. Adverse events are frequent and may cause delay on treatment delivery or drug dose reduction. The survival impact of oxaliplatin reduced dose intensity (RDI) is unknown. Objective Evaluation of survival impact of oxaliplatin RDI in colon cancer patients treated with adjuvant mFOLFOX-6. Material and methods: A consecutive series of colon cancer patients treated with adjuvant mFOLFOX-6 at our institution between 09/2004 and 11/2009. The impact of Oxaliplatin Results There were no differences in age, sex, ECOG, comorbidity, histologic grade and stage distribution between groups. Two hundred and seventy seven (277) patients were identified (53% in group A). Fifty nine percent (59%) of patients completed the 12 mFOLFOX-6 cycles and the median duration of adjuvant chemotherapy was 6,5 months. The mean oxaliplatin dose-intensity was 71% (median 74%). Adverse events led to dose reduction and drug suspension in 53% and 40% of patients, respectively. There were 3 deaths during treatment. The main causes to RDI were grade ≥ 3 hematologic toxicity (47%) and neuropathy (12%) – median cumulative oxaliplatin dose at first neurologic severe event was 1024 mg. There were no differences in PFS and OS between RDI groups, neither after stage stratification. Conclusion In our cohort patient's characteristics and toxicity profile were similar to published trials. FOLFOX conclusion rate was inferior than the described in MOSAIC trial (59% vs 74,7%). Despite the inferior accomplishment rate, there was no impact in PFS and OS in oxaliplatin RDI Disclosure All authors have declared no conflicts of interest.