bluuebunny/crossref_metadata_2025 huggingface dataset:
Cetuximab weekly (q1w) versus every two weeks (q2w) plus FOLFOX4 as first-line therapy in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC).
Authors: Ciuleanu T. , Nikolic V. , Shmueli E. , Vrbanec D. , Plate S. , Krmpotic Z. M. , Dank M. , Purkalne G. , Brodowicz T. , Zielinski C.
Published: February 2017

494

Background: FOLFOX4 + q1w cetuximab is a standard 1st-line regimen in KRAS wt mCRC. This trial evaluated FOLFOX4 + q1w cetuximab (Arm A) and FOLFOX4 + q2w cetuximab (Arm B) as 1st-line therapy in KRAS wt mCRC.

Methods: Pts with KRAS wt mCRC were randomized to q1w cetuximab (400 mg/m2initial dose then 250 mg/m2/wk) or q2w cetuximab (500 mg/m2 every 2 wks). Both arms received FOLFOX4 (folinic acid 200 mg/m2, then 5-FU 400 mg/m2bolus, then 5-FU 600mg/m2 over 22 h on days 1+2, plus oxaliplatin 85 mg/m2 on day 1 q2w). Primary endpoint is objective response rate (ORR) which was analyzed in a protocol specified interim analysis. Secondary efficacy endpoints are progression- free survival (PFS) and overall survival.

Results: From Sep 2007 to Sep 2009, 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized and received ≥1 dose of study treatment, arm A (n=75) and arm B (n=77). Baseline characteristics were well balanced (A vs B): mean age: 57 vs 60 years, Karnofsky Performance Score (PS) 80: 15% vs 18%, PS 90: 45% vs 40%, PS 100: 40% vs 42%, male gender: 40% vs 45%, prior adjuvant or neoadjuvant therapy: 23% vs 17%, metastases at initial diagnosis: 65% vs 64%, and >2 involved organs: 24% vs 29%. Median follow up was 12 months. ORR (CR + PR) was 51% in arm A and 63% in arm B, respectively, the difference between arm B and A was 12% (95% CI: -4% to 27%). Preliminary results for PFS time did not indicate relevant differences between both arms. Mature PFS results will be presented at the symposium. Based on current data, most common grade 3-4 adverse events (≥ 10% in any arm, A vs B) were neutropenia/neutrophil count decreased in 32 vs 34%, rash in 15 vs 16% and diarrhea in 7 vs 10% of the pts.

Conclusions: These data suggest that cetuximab q2w has comparable efficacy and an equivalent safety profile as q1w dosing in combination with FOLFOX4. Data collection and analysis is ongoing.

[Table: see text]

[Table: see text]
Effective management of patients receiving XELOX: Evaluation of impact of dose modifications on outcome in patients from the NO16966, NO16967, and NO16968 trials.
Authors: Cassidy J. , Cox J. V. , Scotto N. , Schmoll H.
Published: February 2017

497

Background: In patients (pts) with metastatic colorectal cancer (MCRC), XELOX is non-inferior to FOLFOX4 in terms of PFS and OS as either first-line (NO16966, Cassidy et al. JCO 2008) or second-line therapy (NO16967, Rothenberg et al. Ann Oncol 2008). In pts with stage III colon cancer (NO16968, Haller et al. ECCO-ESMO 2009), adjuvant XELOX is superior to 5-FU/LV in terms of DFS. While XELOX is generally well tolerated, regional differences in fluoropyrimidine tolerability were noted in a pooled analysis [Rothenberg et al. ASCO GI 2008], leading to use of lower than recommended doses of capecitabine (i.e. 1,000mg/m2 bid d1–15 with oxaliplatin 130mg/m2 d1 q3w) in some countries.

Methods: NO16966, NO16967 and NO16968 protocols included standard dose/schedule modifications for capecitabine, 5-FU and oxaliplatin for treatment-related adverse events (AEs). Safety parameters included AEs, deaths, laboratory parameters, exposure to trial medication, and withdrawals. In NO16966 and NO16967, Kaplan-Meier curves for PFS were developed for pts with no treatment modifications, and pts with dose reductions, treatment interruptions or cycle delays to assess the effect of treatment modifications on efficacy. NO16968 also included a planned analysis of the effect of dose modifications on DFS.

Results: NO16966 included 1335 pts with previously untreated MCRC receiving XELOX or FOLFOX4. NO16967 included 627 pts with previously treated MCRC receiving XELOX or FOLFOX4. NO16968 included 1886 pts with resected stage III disease receiving XELOX or 5-FU/LV; dose modifications were required for capecitabine in 65% and oxaliplatin in 62% of pts in NO16968. Kaplan-Meier curves of PFS (NO16966/NO16967) or DFS (NO16968) for pts who did and did not require dose modifications indicated that the efficacy of XELOX did not appear to be compromised by dose modifications. Indeed, pts who required dose modifications seemed to have a favourable outcome compared with those who did not.

Conclusions: From these data we cannot make a recommendation that initial dosing should be lower than the labeled dose. However, it is clear that dose modification does not seem to impact patient outcome.

[Table: see text]
Prognostic impact of baseline CEA level and surgery of primary tumor among patients with stage IV denovo colon cancer.
Authors: Dawood S. S. , Gonzalez-Angulo A. M. , Eng C.
Published: February 2017

503

Background: Surgical resection of primary tumor among pts with stageIV denovo colorectal cancer is controversial. Prognostic role of baseline CEA level in the same cohort has yet to be defined. The objective of this study was to determine the prognostic value of CEA and surgical resection of primary tumor among pts with stage IV denovo colorectal cancer in the era of biologic therapy and to determine subgroups with improved survival outcome.

Methods: The Surveillance, Epidemiology and End Results Registry was searched to identify patients with stage IV denovo colorectal cancer diagnosed between 2004-2007. Colorectal cancer specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various pt and tumor characteristics and CCS.

Results: 19,437 pts were identified with stage IV denovo colorectal cancer. Median CCS was 15M. Median CCS among pts with primary tumor removed was 20M vs 8M (primary intact; p<0.001). Median CCS among pts who had elevated vs. non elevated CEA was 14M vs 23M (p<0.0001). Among pts who had primary tumor surgery median CCS among pts who had elevated vs. non elevated CEA was 19M vs 29M (p<0.0001). Among pts who had primary tumor and distant disease surgically removed, the median CCS among pts who had elevated vs. non elevated CEA was 24M vs 35M (p<0.0001). By multivariable analysis, pts with elevated CEA had a 51% increased risk of death from colorectal cancer compared to those with a non elevated CEA level (HR=1.51, 95%CI 1.40-1.65, p<0.0001). Pts who underwent primary tumor surgery had a 33% decreased risk of death from colorectal cancer compared to those who did not (HR=0.67, 95%CI 0.58-0.78, p<0.0001). Other factors significantly associated with a decreased risk of death from colorectal cancer included low grade disease, non visceral metastases, surgical resection of metastases, younger age and white race.

Conclusions: In this large population study, elevated baseline CEA level and surgical resection of the primary tumor had a significant impact on survival outcomes. The best prognostic group were those pts with normal baseline CEA level who proceeded to surgical resection for their primary tumor.

No significant financial relationships to disclose.
Oncologic outcomes following radical resection with intraoperative electron radiation therapy in patients with recurrent colorectal cancer.
Authors: Llaguna O. H. , Meyers M. O. , Smith M. B. , Stitzenberg K. B. , Deal A. M. , O'Neil B. H. , Bernard S. A. , Wang A. Z. , Tepper J. E. , Calvo B. F.
Published: February 2017

508

Background: Of the 40,000 rectal cancer patients treated annually, up to 15% will experience a local recurrence (LR). Resection only series for LR report 30–60% positive margin rates. For this reason our institution utilizes intra-operative electron radiation therapy (IOERT) in patients undergoing resection of locally advanced rectal cancer recurrences (LA-RRC). The purpose of this study was to evaluate the oncologic outcomes of patients treated for a LA-RRC with resection and IOERT

Methods: Under IRB approval a prospective database of patients with LA-RRC undergoing resection and IOERT from April 2001 to January 2010 was analyzed. Demographic, clinical, and pathologic variables were collected. The Kaplan-Meier method estimated 5-year overall survival (OS) and Fisher's Exact test's explored associations for developing a LR.

Results: Fifty patients (32 male, mean age 58 ± 11) underwent resection and IOERT (median dose 1500 cGy, energy 9 MeV). Primary procedures included pelvic exenteration (n = 17), APR (n = 10), LAR (n = 7), isolated pelvic/retroperitoneal tumor (n = 7), para-aortic lymphadenectomy (n = 7), and partial colectomy (n = 2). 56% (n = 28) required multi-visceral resections including partial/total cystectomy (n = 14), small bowel resection (n = 10), vaginectomy (n = 6), hysterectomy (n = 3), oophorectomy (n = 3), nephrectomy (n = 2), and other (n = 4). 34 pelvic sidewall resections and 12 partial sacrectomies were required. Margins were R0 in 37 (74%) and R1 in 13 (26%). Median LOS was 10 days and there were no peri-operative deaths. Five-year OS was 32% with a 19-month follow-up of survivors. 32% (n = 16) developed a pelvic LR, of which 2 were isolated and 14 were in the setting of distant metastasis. No difference was noted in OS (p = 0.5) or LR (p = 0.3) in patients with R0 vs. R1 resections. Initial T (p = 0.1), N (p = 0.2), and stage (p = 0.7) were not found to be associated with LR.

Conclusions: This study reveals that resection combined with IOERT provides good local control and reasonable long-term survival in patients with LA-RRC. The similar OS and LR following an R0 and R1 resections could be interpreted as a measure of the beneficial effect of IOERT on microscopic disease.

No significant financial relationships to disclose.
Phase II study of preoperative bevacizumab, capecitabine, and radiotherapy for resectable locally advanced rectal cancer.
Authors: Martinez Villacampa M. , Santos C. , García M. , Navarro V. , Teule A. , Losa F. , Pisa A. , Lema L. , Biondo S. , Salazar R.
Published: February 2017

516

Background: Bevacizumab into chemoradiotherapy appears safe and active in locally advanced rectal cancer (LARC).This study evaluates whether the addition of bevacizumab to capecitabine-based chemoradiotherapy in the preoperative treatment of LARC improves pathological complete response rate (pCR).

Methods: Open-label, unicentric, phase II study in patients with resectable LARC (stage II or III), with or without nodal involvement and no evidence of distant metastases. Treatment schedule of 4-cycles: bevacizumab administered iv on day 1 (10 mg/kg in the first cycle and 5 mg/kg in the following 3 cycles) and capecitabine (900mg/m2/bid) in the 2nd cycle (5 d/wk) concomitantly with radiotherapy 45Gy (25 fractions of 1.8Gy/day) over 5 weeks. Surgical resection was scheduled 6-8 weeks after therapy completion. Preliminary results from ITT analysis are presented.

Results: Of the 43 patients included, 41 comprised ITT population. Baseline characteristics: median age 63 (55-67) years; male 76%; ECOG 0/1 49%/51%; stage T3/N1 80.5%/58.5%; nodal metastases 85%. 39 patients underwent surgery, 9 abdominoperineal and 30 anterior resection. No evidence of metastasis after surgery in 97%. Total mesorectal excision was performed in 69% of patients and 85% underwent R0 resection. Sphincter-preservation was achieved in 79.5%. Downstaging occurred in 82%. Among 39 patients evaluable for pathological response, 7.7% experienced pCR, 69.2% partial response and 20.5% stable disease. Grade 3/4 toxicities: 9.8% lymphopenia (all related to capecitabine and 4.9% to bevacizumab), 2.4% neutropenia (capecitabine-related), 2.4% radiodermatitis (related to RT and capecitabine) and 2.4% vasospastic angina (bevacizumab and capecitabine-related). 13 patients had postoperative complications not treatment-related. The most common were wound infection (6), intra-abdominal collection (3), wound dehiscence (2) and paralytic ileus (2).

Conclusions: Preoperative regimen with bevacizumab, capecitabine and RT is active for LARC with promising results of R0 resection, sphincter- preservation and tumour downstaging as well as manageable toxicity. Further studies are ongoing to confirm these data.

No significant financial relationships to disclose.
Phase I study of everolimus (RAD001) with irinotecan (Iri) and cetuximab (C) in second-line metastatic colorectal cancer: Hoosier Oncology Group GI05-102.
Authors: Myre B. , Yu M. , Picus J. , Bufill J. A. , Harb W. A. , Burns M. , Spittler A. J. , Zeng Y. , Currie C. R. , Chiorean E. G.
Published: February 2017

523

Background: Preclinically, mTOR and EGFR inhibitors are synergistic. We hypothesize that the mTOR inhibitor RAD001 would enhance efficacy and prevent resistance when added to an anti-EGFR agent. The purpose of the phase I portion of this study was to determine the safety and maximum tolerated dose (MTD) of daily RAD001 combined with weekly Iri and C in mCRC.

Methods: Pts who failed first-line therapy, including an Iri-regimen, were treated with Iri 125 mg/m2 weekly x 2 every 3 weeks, C 400 mg/m2 loading dose, then 250 mg/m2 weekly, and escalating doses of RAD001 orally: 5 mg qod, 5 mg qd and 10 mg qd during 21-day cycles, with a “3+3” design. The study was amended after the first 9 pts enrolled, to include stopping rules for excessive toxicity beyond what was expected for diarrhea, nausea/vomiting and febrile neutropenia due to Iri, and skin rash due to C. Enrollment excluded pts with UGT1A1*28, but allowed KRAS mutated mCRC. RAD001 PK was done on C2D1, and archival tumors were analyzed for pharmacodynamic markers.

Results: 28 pts were enrolled, median age 61 y (25-77), 15 male, ECOG PS 0/1 (19/9). Reasons for treatment discontinuation were: PD (7), adverse events (AEs) (6), pt withdrawal, symptomatic deterioration and non-compliance (1 each). Prior to study's amendment* (n=9), 3 pts were not evaluable for DLT due to: Iri intolerance after one dose (1), non-compliance (1) and gr 3 C infusion reaction (1). DLTs and number of cycles are listed in Table. Following protocol amendment, 2 pts had DLT in cohort 3 (gr 3 mucositis), thus the MTD was 5 mg RAD001. The most common grade 3/4 AEs were: diarrhea (10), neutropenia (5), fatigue (4), acne-rash (4), mucositis (2), nausea (2), vomiting (1). Among 19 pts evaluable for response, there were 1 CR, 2 PR, (RR 16%), 9 SD (47%), 7 PD (37%). PK and pharmacodynamic data is ongoing.

Conclusions: The MTD of RAD001 of 5 mg QD with Iri/C weekly is safe and clinically active. A randomized phase II study is near starting accrual.

[Table: see text]

[Table: see text]
Retroperitoneal dissemination of colorectal ovarian metastases: Basis for rationale use of lymphadenectomy.
Authors: Eveno C. , Goárá D. , Tzanis D. , Dartigues P. , Dumont F. , Benhaim L. , Ducreux M. , Elias D.
Published: February 2017

535

Background: Retroperitoneal lymph nodes are a common site of metastases in primary ovarian cancers and primary peritoneal carcinoma, therefore pelvic and paraaortic lymphadenectomy are recommended. Colorectal ovarian metastases are mostly associated to peritoneal carcionomatosis (PC), which treatment is based on complete cytoreductive surgery (CCRS) associated to intraperitoneal chemotherapy (IPC). The aim of this study was to compare the rate of nodal (pelvic, paraaortic) recurrences, between 2 groups of patients (pts) operated on PC with ovarian metastases (OM) or without OM.

Methods: From January 1994 to December 2009, all consecutive women who underwent CCRS plus IPC, were selected from a prospective database. Demographics, tumor characteristics, surgical procedures and chemotherapy, were analyzed and compared.

Results: One hundred and five pts were identified; 63 (60%) had ovarian metastasis (synchronous or metachronous). Groups were comparable for all variables, except for the median peritoneal cancer index which was lower in the OM group (9 vs.10.5, p<.05). Nodal recurrences were diagnosed in 19 pts (18%), in paraaortic nodes in 14 pts (74%), pelvic nodes in 7 pts (36%), both in 2 pts (10%) and were associated to other relapse in 15 pts (80%). All these nodal recurrences occurred in the OM group (30% vs. 0, p<.001). After a median follow-up of 74 months (10-196), 3-year overall survival rate was greater in pts without nodal recurrences (71 vs 41 %, p=0.37) and at the end of the study, there was significantly more patients died of disease in case of nodal recurrence (24/44 vs 5/19, p=.04).

Conclusions: Nearly one third of patients with ovarian metastases experienced paraaortic and pelvic nodes recurrences. This may due to the specific pattern of lymphatic spread of ovary, well known in primary carcinomas. Therefore, systematic lymphadenectomy should be studied in patients with colorectal ovarian metastases treated in curative intent.

No significant financial relationships to disclose.
Phase Ib study of drozitumab combined with first-line FOLFOX plus bevacizumab (BV) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Rocha Lima C. S. , Baranda J. C. , Wallmark J. , Choi Y. , Royer-Joo S. , Portera C. C.
Published: February 2017

546

Background: Drozitumab is a monoclonal antibody that triggers tumor cell apoptosis by selective agonistic interaction with the Apo2 ligand/TNF-related apoptosis-inducing ligand death receptor 5. This study assessed the safety of drozitumab combined with FOLFOX+BV as first-line therapy in mCRC pts.

Methods: Multicenter, open-label study of 2 sequential dose cohorts. Cohort 1 = 3.5mg/kg after 5 mg/kg loading dose (n=3); Cohort 2 = 7mg/kg after 10mg/kg loading dose (n=6). Pts were treated on 14-day cycles (drozitumab, FOLFOX, and BV 5mg/kg on Day 1 of cycle) until disease progression or toxicity. Dose-limiting toxicity (DLT; primary outcome measure) was assessed through 2 cycles (Days 1-28). Adverse events (AE) were recorded through all cycles. Response was assessed by RECIST.

Results: A total of 9 pts received 1-22 cycles (median 11) of drozitumab. No DLTs occurred. Most frequent AEs were neutropenia (89%), diarrhea (78%), nausea (78%), fatigue (67%), and anemia (56%). Most frequent Grade ≥3 AEs were fatigue (33%), anemia (22%), diarrhea (22%), hypokalemia (22%), and neutropenia (22%). One pt was discontinued from study drug due to serious AE of vancomycin-resistant enterococcal sepsis assessed as unrelated to drozitumab. Other reasons for discontinuation included disease progression (4 pts), physician's decision (3 pts) and patient's decision (1 pt). Among the 9 patients, best responses included five Partial Responses (2 confirmed and 3 unconfirmed), three Stable Disease, and one missing. The sponsor stopped the study enrollment early for reasons unrelated to safety or efficacy.

Conclusions: Addition of drozitumab to first-line FOLFOX+BV was well tolerated overall in these mCRC pts. AEs were similar to those previously reported for FOLFOX+BV alone. Tumor responses suggest no adverse interactions between drozitumab and the chemotherapy evaluated in this study.

[Table: see text]
A randomized, double-blind, placebo-controlled trial for prevention of oxaliplatin-induced neuropathy symptoms with pregabalin.
Authors: Karthaus M. , Karapetis C. S. , Brown M. , Pavlakis N. , Trarbach T. , Marschner N. , Duerk H. A. , Manzione L. ,   Pregabalin Study Group
Published: February 2017

553

Background: Sensorial peripheral neuropathy (PNP) is a major limitation for pts receiving oxaliplatin-based ctx for CRC. Pregabalin is widely used for treatment of oxaliplatin-induced PNP. We evaluated the efficacy of pregabalin vs. placebo for the prevention of paresthesia from the onset of oxaliplatin-based ctx over each cycle.

Methods: Rd, db, placebo-controlled study in adult CRC pts with ECOG 0-2 to undergo a new oxaliplatin/5-FU/FA-based ctx. Pts were excluded if they had neuropathic pain or other of painful paresthesia prior to baseline. Paresthesia, dysesthesia, and pain were rated on a numerical scale (NRS 0-10) every day. Primary endpoint was the time of onset of persistent symptoms (NRS >4).

Results: Of the 69 screened pts, 64 were randomized and 61 received study medication (32 pregabalin vs. 29 placebo). Pts were balanced in both arms regarding age, sex, stage, and ctx. There were no differences between both treatment groups for all PNP parameters at any cycle. One pt in both arms developed paresthesia (5.3%) after 9 cycles of ctx, 1 pt had persistent pain (placebo arm). During the follow-up period persistent paresthesic, dysesthesic, and persistent pain developed in 2 vs. 1, 2 vs. 2, and 0 vs. 2 pts, respectively. The study was terminated after a blinded data review found that there were very few events of persistent symptoms, which was then confirmed an interim analysis. Nausea and anorexia were the most frequently reported AE in both groups.

Conclusions: The results of this study, which was terminated early at interim analysis, is that too few patients developed persistent symptoms to allow any meaningful treatment difference for prevention of neuropathic pain related to oxaliplatin by pregabalin. There remains an unmet need for oxaliplatin-induced PNP with new trial design issues in this field urgently needed.

No significant financial relationships to disclose.
Primary non-Hodgkin lymphoma of the colon among patients in the Veterans Affairs Health System.
Authors: Tashi T. , Thota R. , Krishnamurthy J. , Sama A. R. , Aldoss I. T. , Gonsalves W. , Ganti A. , Townley P. , Silberstein P. T. , Subbiah S.
Published: February 2017

554

Background: Primary non-Hodgkin lymphoma (NHL) of the colon is rare. There are no randomized controlled trials describing treatment outcomes for this tumor. We provide the largest descriptive study of this tumor to date.

Methods: Retrospective analysis of 109 patients diagnosed with primary non-Hodgkin lymphoma of the colon from 1995 to 2008 was done via the Veteran's Affairs Central Cancer Registry. By definition, all cases presented with a lymphomatous involvement of the colon as the first manifestation of their disease with no previous diagnosis of NHL of any type or site. Demographic, staging, histology, treatment, and outcome data was recorded. Lymphomas were classified as aggressive versus indolent based on their histology.

Results: There were 36,260 colon cancers diagnosed in 1995-2008 of which 109 (0.3%) were primary non-Hodgkin colon lymphomas. The median age of diagnosis was 67 years. 55 pts had aggressive disease, 27 pts had indolent disease, and 27 pts had inadequate histological data. Diffuse large B cell lymphoma (73%) was the most common aggressive lymphoma whereas it was marginal zone (56%) in the indolent group. The indolent group had 5- year survival rate of 76.9% compared to 48.6% for the aggressive group. Both groups had received different treatment regimens as seen in the Table with variable mean survival outcomes.

Conclusions: Our data suggests addition of postoperative adjuvant chemotherapy appears superior to surgery alone in the treatment of aggressive disease whereas it does not appear to provide any benefit in the treatment of indolent disease. However, patient numbers are too small to draw definite conclusions and warrant future investigation in multinational randomized fashion.

[Table: see text]

No significant financial relationships to disclose.
Effectiveness and safety in very elderly patients treated by bevacizumab (BV) plus chemotherapy in first-line therapy of metastatic colorectal cancer: Results of ETNA, a French cohort study.
Authors: Smith D. , Rouyer M. , Noize P. , Lassalle R. , Bernard O. , Burki F. , Guichard P. , Ravaud A. , Moore N. , Fourrier-Ráglat A. ,   ETNA Study Group
Published: February 2017

555

Background: In view of the ageing population, oncogeriatrics has become a priority for public health. Elderly cancer patients are often excluded from clinical trials and there is no therapeutic standard for their care management. Cohort studies have been conducted in US and Europe but not in France. The ETNA study aimed to describe BV use and survival outcomes in real-life practice. Here, the population aged >75 years was compared to that aged >75.

Methods: ETNA is a cohort study conducted in 28 French centers that included 411 patients initiating BV between Jan 2006 and Dec 2007, with 24 month follow-up.

Results: Fifty-one patients (12.4%) of the cohort were over 75 years old: mean age 78.3 years (vs 61.9 years for the rest of the cohort), male 66.7% (vs 56.1%), ECOG≥2 17.6% (vs 10.8%). BV was combined with FOLFIRI/XELIRI in 88.2% of patients aged >75 years (vs 87.5%) and FOLFOX/XELOX in 11.8% (vs 12.2%). Median duration of BV treatment was 5.6 months (m) (vs 5.5 m), and median duration of the 1st-line was 10.3 m (vs 9.8 m). More patients >75 years had treatment-free intervals (39.2% vs 28.6%), and 13.7% had a maintenance therapy (vs 12.8%). Curative surgery performed in 15.7% of patients (vs. 20.6%). Among the 43 patients who discontinued the 1st-line, only 9.3% discontinued BV prematurely (vs 18.2%). The incidence of any grade-3/4 adverse event was 43.1% (vs 41.7%). In-line with the known safety profile of BV (any grade), hypertension was observed in 21.6% (vs 18.9%), proteinuria 23.5% (vs 27.2%), there were no GI perforations (vs 0.3%), thrombotic events 5.9% (vs 7.8%), and grade 3/4 arterial thrombotic events 2.0% (vs 0.6%). The 1-year OS rate was 78.0%, 95%CI [63.9-87.2] (vs 80.5%, 95%CI [76.0-84.2]) and the median OS was not reached for both groups. The median PFS was 10.6 m, 95%CI [9.0-12.8] (vs 9.9 m, 95%CI [9.3-11.1]).

Conclusions: Effectiveness and safety of BV plus chemotherapy in elderly patients were similar to those of the rest of the ETNA cohort. Estimations of survival outcomes (1-year OS rate, median OS and PFS) were also comparable to those found in elderly patients (75-80 years) from the BRITE cohort (72.0%, 20.3 m and 10.0 m, respectively).

No significant financial relationships to disclose.
Are there differences in chemotherapy (CT) administration and outcomes in elderly patients (pts) diagnosed with colorectal cancer (CRC)?
Authors: Sehgal R. , Krug C. E. , Reifer J. , Tria Tirona M. , Douglas W. G. , Edwards P. , Gress T. W.
Published: February 2017

557

Background: CRC is the third most common cancer in men and women in the United States. The median age at diagnosis is 70 years (yrs). Controversy exists in the literature regarding benefit from CT in elderly pts with CRC. We performed a retrospective study to evaluate CT rate and its benefit in different age groups of pts with CRC.

Methods: Data on pts diagnosed with CRC from 1993-2008 were collected from the Cancer Information Resource File. Complete data on age, gender, stage, tumor characteristics, treatment, and overall survival (OS) were available on 32,177 pts and were analyzed by age in four categories: < 50, 50-69, 70-79, and ≥ 80 yrs.

Results: Of 32,177 pts, 7% were < 50, 35% were 50-69, 32% were 70-78, and 26% were ≥ 80 yrs. The table reports pt demographics, median OS (MOS) by age and stage, and rates of CT by age and stage. As reported in the table, use of CT declined with advancing age, regardless of stage. Multivariate Cox regression analysis simultaneously adjusted for age at diagnosis, gender, race, stage, and grade revealed that CT was associated with reduced mortality in all age categories: < 50 yrs, HR 0.75; 50-69, HR 0.61; 70-79, HR 0.53; and ≥ 80, HR 0.55 (all p < 0.01).

Conclusions: Older pts receive CT less frequently than younger pts. The use of CT in the elderly was associated with a reduced mortality, similar to that seen in younger pts. Younger pts were more likely to present with stage IV disease when compared to the elderly. Randomized, prospective trials are required to explore the differences noted.

[Table: see text]

No significant financial relationships to disclose.
Radioembolization of unresectable hepatic metastases using yttrium-90 microspheres in heavily pretreated colorectal cancer.
Authors: Hill M. E. , Mulcahy M. F. , Lewandowski R. , Rademaker A. , Salem R.
Published: February 2017

559

Background: Yttrium-90 (Y90) microsphere liver-directed treatment has previously demonstrated the ability to provide disease stabilization to patients with liver-dominant metastatic colorectal cancer.

Methods: We conducted a retrospective analysis of 36 patients with metastatic colorectal cancer who had undergone Y90 liver-directed therapy between November 2001 and March 2009. All patients had previously received 5-fluorouracil, irinotecan, and oxaliplatin and had unresectable hepatic metastases, with or without extrahepatic metastases.

Results: Thirty-six patients with a mean age of 58 were included in the analysis. Twenty patients had both hepatic and extrahepatic metastatic disease and 16 had liver-confined metastatic disease at the time of first Y90 treatment. Radiologic response rate with stabilization of liver metastases was 72%. Median survival from time of diagnosis of liver metastases and from time of first Y90 treatment was 31.7 months and 9.4 months, respectively. One patient is still alive. Nine patients received only one Y90 treatment, 20 patients received two treatments, and 7 patients received three treatments. One-year survival from first Y90 treatment was 47%, and 53% of these patients had no extrahepatic metastatic disease prior to therapy, 41% had minimal extrahepatic disease, and 6% had significant extrahepatic disease. Fifty-three percent of patients survived less than one year after the first Y90 treatment. Of these, 36.8% had no evidence of extrahepatic metastatic disease prior to first Y90 therapy, 31.6% had a small volume of extrahepatic disease, and 31.6% had extensive extrahepatic disease.

Conclusions: Liver-directed therapy with Y90 was observed to control the growth of unresectable metastatic liver disease in the majority of patients with heavily-pretreated colorectal cancer. A significantly smaller proportion of patients who survived a year or more had extensive extrahepatic mestastatic disease at the time of first Y90 treatment than those who survived less than a year. This suggests a potential survival advantage of Y90 liver-directed treatment in patients with primary liver metastatic disease and minimal extrahepatic disease.

[Table: see text]
MFOLFOX6 with oxaliplatin stop-and-go strategy and oral S-1 maintenance therapy in advanced colorectal cancer: CCOG-0704 study.
Authors: Nakayama G. , Kodera Y. , Yokoyama H. , Okuda N. , Fujii T. , Nakao A.
Published: February 2017

569

Background: In metastatic colorectal cancer (mCRC), a combination of leucovorin and fluorouracil with oxaliplatin (FOLFOX) is one of the standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. The aim of this study was to evaluate modified FOLFOX6 (mFOLFOX6) with the intermittent oxaliplatin treatment and maintenance therapy with S-1, oral fluoropyrimidine derivative, in the first-line treatment of mCRC.

Methods: Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-fluorouracil bolus 400 mg/m2 and 5-fluorouracil continuous 2400 mg/m2, every 2 weeks) followed by maintenance therapy with oral S-1 (S-1 80- 120mg/body days 1-28, every 6 weeks). Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or tumor progression. The primary study end point was duration of disease control (DDC).

Results: Twenty of the 30 patients (66.7%) who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in thirteen patients (43.0%). Median DDC was 9.3 months. Median progression-free survival (PFS) was 7.9 months. Overall response rates and disease control rates were 40.0% and 86.6% for the initial mFOLFOX6, 25.0% and 55.0% for S-1 maintenance therapy and 23.1% and 76.9% for mFOLFOX6 reintroduction. Twenty-eight patients (93.3%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.3%).

Conclusions: The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible first-line treatment for Japanese mCRC patients. Further prospective randamized control study is warranted.

No significant financial relationships to disclose.
Adjuvant capecitabine treatment for stage III colon cancer in Japanese patients (KSCC0803).
Authors: Kitazono M. , Emi Y. , Kakeji Y. , Sakaguchi Y. , Samura H. , Ogata Y. , Natsugoe S. , Shirouzu K. , Tokunaga S. , Maehara Y. ,   Kyushu Study Group of Clinical Cancer (KSCC)
Published: February 2017

571

Background: Capecitabine was approved in Japan in 2007 for the adjuvant treatment of stage III colon cancer based on Japanese clinical trial data in advanced and recurrent colorectal and breast cancers as well as data from the Phase III X-ACT trial. For the current study, we aimed to clarify compliance and tolerability of adjuvant treatment with capecitabine in Japanese patients. The study was entered in the UMIN clinical trial registry (UMIN000001444) by the Kyushu Study Group of Clinical Cancer (KSCC). Ethical approval was granted by the institutional review board of each hospital involved.

Methods: Based on completion rates from the X-ACT trial we enrolled 97 patients with R0 stage III colon cancer who had histologically confirmed disease and had undergone curative resection (3D2 lymph node dissection). Patients were given oral capecitabine therapy (2,500 mg/m2/day; days 1–14 q3w; eight cycles) within 8 weeks of surgery. The proportion of patients completing eight cycles of treatment per protocol was the primary endpoint, and adverse event (AE) rate was analyzed as a secondary endpoint.

Results: Treatment completion in the total patient population was 66.0% (64/97 patients; 95% CI: 55.7–75.3%) and in the per protocol population (PPP) was 70.3% (64/91; 95% CI: 59.8–79.5%). AEs leading to treatment discontinuation included hand-foot syndrome (HFS; n=7), hematotoxicity (n=5) and increased hepatic activity (n=4). Grade 3/4 AEs of note included HFS (22.7%), neutropenia (7.2%), diarrhea (2.1%), and increased bilirubin (0.0%). Of note, any treatment delay >3 weeks in the current trial was considered a withdrawal. In the X-ACT trial, delays of any duration were permitted. Using the X-ACT criteria the completion rate for the PPP in this study was 80.2%, comparable to the figure reported in X-ACT.

Conclusions: Our results confirm those of previous global phase III studies and show that capecitabine is well tolerated in both global and Japanese-only populations, with similar high completion rates in both.

[Table: see text]
Primary signet ring cell carcinoma of colon: Retrospective analysis of VACCR database.
Authors: Thota R. , Tashi T. , Gonsalves W. , Murukesan V. , Townley P. , Ganti A. , Silberstein P. T. , Subbiah S.
Published: February 2017

58

Background: Signet ring cell carcinoma accounts for less than 1% of all colon cancers. We examined the clinical pathological features and prognosis of signet ring cell carcinoma of colon and compare it with mucinous and non-mucinous adenocarcinoma of colon.

Methods: A total of 206 patients diagnosed with signet ring cell carcinoma from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected.

Results: Out of 206 patients, 173 (83.9%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous and non-mucinous adenocarcinoma of colon. Pathological T-stages were as follows: T1 = 2.9%, T2=5.3%, T3=33.9%, T4= 25.7%, and unknown 32%. Of the total, 22.3% were located in caecum, 21.8% in ascending colon, 15.5% in sigmoid colon, 7.7% in appendix and hepatic flexure of colon, 11.1% in transverse colon, 2.9% in splenic flexure and 4.4% in descending colon. 33.5% were lymph node positive, 34.6% were lymph node negative, and 31.8% were unknown. Histologically grade 3 (55.4%) was most commonly reported followed by grade 2 (7.3%), grade 1 (2.5%), grade 4 (1.9%)and in 33% grade was unknown. 41.3% patients received only surgery while 34% received surgery with adjuvant chemotherapy, 7.3% received chemotherapy alone and 7.8% patients received either chemotherapy, radiation or hormonal therapy alone, 9% did not receive any therapy. 1 year, 3 year and 5 year survivals for signet ring cell cancer compared to adeno carcinoma was 60% vs 80%, 33% vs 60%, and 24% vs 47% respectively. Median survival of signet ring cell carcinoma compared to mucinous and non mucinous adenocarcinoma was 19 months, 48 months and 62 months respectively.

Conclusions: Signet ring cell carcinoma of colon has poor survival rates than the other histological subtypes. Signet ring cell carcinoma presents at an earlier age, higher tumor grade and advanced stage at diagnosis when compared to mucinous and non-mucinous adenocarcinoma of colon. Due to rarity of this disease further multi-institute studies are required for in-depth understanding and analysis of this disease.

No significant financial relationships to disclose.
Effectiveness of FIr-B/FOx and liver metastasectomies in liver-only metastatic colorectal cancer (MCRC).
Authors: Bruera G. , Cannita K. , Lanfiuti Baldi P. , Santomaggio A. , Marchetti P. , Nuzzo G. , Antonucci A. , Ficorella C. , Ricevuto E.
Published: February 2017

582

Background: Effectiveness of liver metastasectomies was evaluated in liver-MCRC patients treated with FIr-B/FOx association in a previous phase II study (Bruera et al, submitted 2010).

Methods: Treatment schedule: 12h-timed-flat-infusion/5-Fluorouracil 900 mg/m2 days 1-2, 8-9, 15-16, 22-23; Irinotecan 160 mg/m2, Bevacizumab 5 mg/kg days 1, 15; Oxaliplatin 80 mg/m2 days 8, 22; every 4 weeks. Resection rate, activity, efficacy were analysed and compared in liver-only versus multiple metastatic sites and single versus multiple liver metastases.

Results: Liver-MCRC were 33: liver-only 22 patients (67%); multiple metastatic sites 11 patients (33%). Liver metastasectomies were performed in 13 patients (11 R0, 84.6%): 26% of 50 MCRC patients enrolled in the FIr-B/FOx phase II study; 39% of liver-MCRC patients; 54% of liver-only, 6 of 9 (67%) single and 6 of 13 (46%) multiple liver metastases; one liver and lung metastasectomy. Pathologic complete responses (CRs) were 2 (15%); downsizing with modification of surgical resectability, 9 patients (41%); conversion rate of unresectable liver metastases, 83%. Overall activity, including 3 clinical CR, in liver-only patients, 68%. ORR, PFS, OS, respectively: in liver-MCRC patients, 84%, 11 and 23 months; in liver-only metastases, 86%, 17 and 44 months; in liver metastasectomies, 100%, 21 months (PFS from liver surgery 10 months) and 47 months. Significantly increased efficacy: PFS and OS in liver-only versus multiple metastatic sites (p 0.006 and 0.011, respectively) and single versus multiple liver metastasis (p 0.026 and 0.022, respectively).

Conclusions: FIr-B/FOx chemotherapy increases resection rate of liver metastases, thus significantly improving efficacy of liver-only MCRC patients.

No significant financial relationships to disclose.
Quality-of-life measurements in patients receiving radiation therapy for colorectal malignancies as compared to other gastrointestinal malignancies.
Authors: Samuelson B. T. , Fromme E. K. , Waller J. , Thomas C. R.
Published: February 2017

587

Background: Therapy for GI malignancies has long been known to have a marked impact on quality of life, yet this relationship remains poorly understood.

Methods: A retrospective, IRB-approved chart review was performed of 722 patients receiving RT for any cancer diagnosis between 1/1/2006 and 12/31/2008. Subjects completed the Functional Assessment of Cancer Therapy General (FACT-G) questionnaire before and after RT. Pre- and immediately post-RT course scores were compared using student t-tests with Bonferroni correction for multiple comparisons (5 comparisons, alpha =.01).

Results: 722 of 1369 (52.7%) possible patients participated in the database. Complete pre and post RT spirituality data were available for 73 (64.6%) patients with GI malignancies. Average age was 62 years, 58 (79%) were male and 52 (71%) received definitive treatment. 27 (37%) had esophageal or gastric cancer, 22 (30%) had colorectal cancer and 24 (33%) had other GI malignancies such as pancreatic or hepatobiliary. Colorectal cancer patients fared better in overall QOL as compared to esophageal and gastric patients, pancreatic and hepatobiliary patients and patients with GI malignancies as a whole, and were the only group in which decline in overall QOL as measured by the FACT-G (77.22 to 73.08, p=0.216) did not reach or approach significance. This appeared to be largely driven by differences in physical and especially functional well-being, in which colorectal patients demonstrated the smallest decline (16.14 to 15.59, p=0.466) of any group. Colorectal patients did, however, demonstrate a larger decline in physical well-being (22.35 to 18.05, p=0.010) and overall QOL than did all-comers with any primary malignancy (22.1 to 19.4, p<.001) and (81.3 to 78.9, p<.001) respectively.

Conclusions: Physical and functional well-being, as well as overall quality of life are known to decline in patients with GI malignancies. Patients with colorectal disease appear to fare better than those with esophageal, stomach, pancreatic or hepatobiliary malignancies by these measures. Additional investigations are warranted to further define these differences.

No significant financial relationships to disclose.
What is the benefit for patients suffering from metastatic colorectal cancer (mCRC) after bevacizumab-based regimen (BBR), cetuximab-based regimen (CBR), and panitumumab (P)?
Authors: Metges J. , Ramée J. , Raoul J. , Gourlaouen A. , Porneuf M. , Capitain O. , Achour N. , Egreteau J. , Douillard J. , Grude F.
Published: February 2017

595

Background: Metastatic colorectal cancer (mCRC) management has been clearly improved by targeted therapies such as anti VEGF and /or anti-HER1 drugs. The evaluation of the use of targeted therapies in the real world is strategic to assess health politics. OMIT Bretagne-Pays de la Loire is a network of private and public cancer centers that has been leading cohort studies evaluating Folfiri-bevacizumab treatment, the cost of targeted therapies and the succession of targeted therapies.

Methods: The purpose of this study is to evaluate the benefit and safety of three consecutive targeted therapies in patients with KRAS wild-type unresectable mCRC. Sex, age, localization of the primary tumor site, successive chemotherapeutic regimens, toxicities, response rates, progression free survival and overall survival have been studied.

Results: 34 patients (22 men, 12 women, median age 63 years [43-82]) have been prospectively recruited between 2003 and 2010. All of them received bevacizumab specially in association with FOLFIRI, cetuximab in association with irinotecan, panitumumab as monotherapy and others chemotherapies than FOLFOX, FOLFIRI, XELOX. The primary tumor site was colon (71%), junction (5%), and rectum (24%). 22 patients had metastatic colorectal tumor, 28 were operated on their primary tumor and 12 underwent resection after one line of treatment. Patients received successively 3 to 8 different lines of treatment for progressive mCRC. Toxicities of targeted therapies were manageable. Objective responses were observed in 38% (13) of the patients treated with BBR, 37% (11) treated with CBR and 25% (6) treated with P. Disease stabilization was achieved in 32% (11) of the patients treated with BBR, in 10% (3) with CBR and in 8% (2) with P. PFS at 80 months is 15%. Median OS from first metastatic line at death was 47.43 months (24.23-70.84). PFS and OS curves will be shown during the meeting.

Conclusions: Our study clearly shows that patients receiving successively the three schedules (BBR, CBR, P) have a high overall survival with manageable side effects.

No significant financial relationships to disclose.
High linear energy transfer (LET) radiation therapy in recurrent, metastatic, or unresectable rectal adenocarcinoma.
Authors: Paximadis P. , Elliott D. , Shields A. F. , Philip P. A. , Weaver D. W. , Konski A. A.
Published: February 2017

612

Background: The purpose of this study was to retrospectively analyze the outcomes of patients with recurrent, metastatic, or unresectable rectal adenocarcinoma treated with mixed beam photon and high LET radiotherapy.

Methods: Between 1995 and 2005, the high LET database was queried to identify patients with rectal adenocarcinoma. Local control and overall survival (OS) were calculated using the Kaplan-Meier method. Acute and chronic toxicities were graded using the common terminology criteria for adverse events (CTCAE) v4.0 grading system. Biological equivalent dose (BED) was calculated for tumor and normal tissue of both the photon dose and neutron dose for 10 patients.

Results: 11 patients with recurrent, metastatic, or unresectable rectal adenocarcinoma were identified as being treated with mixed photon-neutron radiation. The median age of patients in the study was 58 (range: 38-79). There were 8 male patients and 3 female patients. Median follow-up was 6 months (range: 4-76 months). Patients received a median photon dose of 40Gy (range: 26-50.4Gy) and a median neutron dose of 8nGy (range: 6-10nGy). Seven patients received radiation given concurrently with 5-FU. The median OS was 16 months (range: 4-76 months), with 1 and 2-year OS of 56% and 22%, respectively. Local control was achieved in 9 of 11 (82%) patients. Local progression occurring in two patients occurred at 5 months after completion of RT. The median tumor BED in patients achieving local control was 72.5 Gy (range: 57.1-83.5 Gy). There was a nonsignificant difference in median normal tissue BED of patients with grade 3-4 late toxicity of 104.8 Gy (range: 81.1-115.1 Gy), compared with 95.3Gy (range: 89.0-104.6 Gy) for those patients with grade 1-2 late toxicity.

Conclusions: Our experience demonstrates that treatment of unresectable rectal tumors with mixed photon-neutron achieved excellent local control. With the added capabilities of intensity modulated neutron radiation therapy (IMNRT), the incidence of treatment-related morbidity may be improved while taking advantage of the superior tumor control that high-LET radiation can impart.

No significant financial relationships to disclose.