bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of a germ-line variant in the K-ras 3’ untranslated region with response and progression-free survival in patients with mCRC treated with single-agent cetuximab (IMCL-0144) or in combination with cetuximab (EPIC) independent of K-ras mutation status
Authors: Winder T. , Zhang W. , El-Khoueiry A. , Yang D. , Pohl A. , Lurje G. , Rowinsky E. , Khambata-Ford S. , Langer C. , Awad M. , Lenz H. 
Published: August 2020

4061 Background: Recent studies have found K-ras mutation status predicts response to EGFR inhibitors in mCRC. An in vitro study demonstrated let-7 microRNA family can regulate RAS expression by binding to the 3’UTR of RAS gene. Chin et al found a SNP in a let-7 microRNA complementary site (LCS) in the K-ras 3’ UTR increases cancer risk in NSCLC. We tested the hypothesis whether this SNP may be associated with clinical outcome in 130 mCRC patients enrolled in IMCL-0144 trial and in 186 pts enrolled in EPIC trial independent of K-Ras mutation status in the tumor. Methods: K-ras lcs 6 SNP was tested in 130 mCRC patients enrolled in IMC-0144 phase II clinical trial (single agent cetuximab) and in 186 mCRC patients enrolled in a second line phase III trial of cetuximab plus irinotecan versus irinotecan alone (EPIC). Genomic DNA was extracted from dissected formalin fixed paraffin embedded tumor tissue and K-ras mutation status and the polymorphism were analyzed using direct sequencing and PCR-RFLP technique. Results: The G harboring allele frequency in K-ras lcs6 was 8% in IMC-0144 and 11% in EPIC. K-ras lcs6 polymorphism was significantly associated with tumor response in patients with wild type K-ras in IMC-0144. The 12 pts harboring a G allele (TG+GG) had a 42% partial response (PR) rate compared to 55 pts with TT genotype with only 9% PR.(p=0.02, Fisher's-exact test). However, pts with TT genotype enrolled in EPIC treated with CPT-11 and cetuximab with mutant K-ras had a significantly better PFS of 12 weeks (95% CI 6.4–18) compared to those harboring the a G allele with median PFS of 6.4 weeks (95% 5.7–7) (p=0.037. log-rank test). There was no association between this polymorphism and clinical outcome in patients with wild type K-ras enrolled in EPIC. In a multivariate analysis the polymorphism remained independently associated with PFS in EPIC. Conclusions: Our data suggest for the first time that the functional germline polymorphism in K-ras lcs6 may be a potential predictive marker in mCRC patients treated with cetuximab-based chemotherapy independent of K-ras mutation status. This finding warranted further confirmative clinical trials. [Table: see text]
Association of CD133 polymorphisms and clinical outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with either first-line 5-FU + bevacizumab (BV) or second-line irinotecan (IR)/cetuximab (CB) or IR alone
Authors: Pohl A. , Zhang W. , Yang D. , Lurje G. , Ning Y. , Khambata-Ford S. , Langer C. , Kahn M. , Teo J. L. , Lenz H. J. 
Published: August 2020

4062 Background: CD133 has been routinely used to identify colon cancer stem cells. A recent study indicated that elevated levels of CD133 plasma mRNA correlated with colon cancer recurrence. Furthermore plasma levels of CD133+ progenitor cells have been found to be decreased after treatment with BV. We tested whether potentially functional frequently occurring germline variations in the 3’UTR-region of the CD133 gene (rs2240688, rs3130 and rs2286455), might be associated with clinical outcome in first- and second-line treated mCRC pts. Methods: Genomic DNA was extracted either from peripheral blood (79 pts, who were enrolled in a phase-II clinical trial with FOLFOX/BV or XELOX/BV) or formalin-fixed paraffin-embedded tumor samples (186 pts, who were enrolled in the EPIC phase III clinical trial, US-sites only) of mCRC pts. Pts received either first-line treatment with FOLFOX/ BV (33 pts) or XELOX/BV (46 pts) or second-line treatment with CB/IR (84 pts, arm A) or IR (102 pts, arm B) alone. Genotyping was performed using PCR-RFLP assays. Results: 79 pts (47 men, 32 women) received FOLFOX/BV or XELOX/BV. Radiologic response: 43 pts (54%) CR/PR, 35 pts (45%) SD/PD. Median PFS was 10.8 months (95%CI: 8.1–14.9). The second cohort consisted of 186 pts (103 men, 83 women). Radiologic response: Arm A 11 pts (13%) CR/PR, 73 pts (87%) SD/PD. Arm B 6 pts (6%) CR/PR, 96 pts (94%) SD/PD. Median PFS (arm A) was 3.0 months (95%CI: 2.4–4.1) vs. 2.7 months (arm B,95%CI: 2.2–2.9). Combined analysis of rs2286455 and rs3130 showed a significant association with PFS (p= 0.010, log-rank test) in pts receiving FOLFOX/BV or XELOX/BV. In pts receiving IR alone rs2240688 was significantly associated with OS (p=0.0128, log-rank test). Multivariate analysis showed a significant association with PFS in first-line setting for rs2286455 and rs3130 (adjusted p=0.012) and a trend in second-line setting for rs2240688 (adjusted p=0.086). Conclusions: These are the first data to show that polymorphisms in CD133 predict outcome in mCRC pts in first- and second- line setting, suggesting that CD133 may be a potential predictive marker. These results need to be confirmed in larger prospective studies. [Table: see text]
Coexpression of matrix metalloproteinase-7 (MMP7) and phosphorylated insulin growth factor receptor I (pIGF-IR) as predictors of resistance to anti-EGFR therapy in advanced colorectal cancer (ACRC): A GEMCAD study
Authors: Horndler C. , Gallego R. , Alonso V. , Alonso V. , Escudero P. , Jimeno M. , Garcia-Albeniz X. , Fernandez-Martos C. , Castellví-Bel S. , Maurel J. 
Published: August 2020

4063 Background: IGF-IR is supposed to have anti-apoptotic and mitogenic properties in colorectal cancer and by transactivation can promote EGFR phosphorylation. MMP-7 is produced by colorectal cancer cells and by degrading IGFBP-3 can activate IGF-IR. Methods: We retrospectively investigated the role of pIGF-IR immunoreactivity (IHC) (Rubini) and MMP-7 IHC in primary CRC or metastases, to predict response rate (RR), progression free survival (PFS) and overall survival (OS) in ACRC patients (pts) treated with either cetuximab or panitumumab as second or third line therapy. RAS mutational status of codons 12/13 was determined using quantitative PCR-based assay. CT scans were done every 1.5–2 months (m) until progressive disease. Results: A total of 99 pts with available tissue from 168 pts with ACRC treated with anti-EGFR therapy in 4 Spanish Institutions, were analysed for RAS mutational status, pIGF-1R and MMP-7. There were no major differences in RR (18.8 vs 16%), PFS [3.3 vs. 3.1 months (m)] and OS (7.7 vs. 7m) between the whole and selected cohort. Fifty-seven (57.6%) pts were male, the median age was 62 (range 34–79) years, the median number of previous chemotherapy lines was 2 (range 1–3) and PS was distributed as follow: PS0, 17 (17.2 %) pts; PS1, 66 (66.7%) pts and PS2, 16 (16.2%) pts. Expression of MMP-7 and pIGF-1R were observed in 48 (48.5%) and 52 (52.5%) pts respectively. Co-expression of MMP-7 and pIGF-1R [Double Positive (DP)] was observed in 26 (26.3 %) pts and in 16 (24%) out of 66 RAS wild-type (WTRAS) pts. There was no association between RAS mutational status and DP (p=0.52). DP progressed more than non-DP pts both in the overall sample (73 vs. 43%, p=0.028) and in WTRAS pts (75 vs. 32%, p=0.011). In the subset of WTRAS pts, DP pts also have a poorer OS: 6.4 (95% CI 5.8–7.1) m vs. 8.6 (95%CI 6.0–11.3) m (p=0.005), and a trend for worse PFS 2.7 vs 4.0 m (p=0.11). Conclusions: Co-expression of pIGF-1R and MMP7 is associated with resistance to anti- EGFR therapy in WTRAS pts. Our study suggests that pts with WTRAS and DP could be a target population to assay new anti-IGF-1R compounds. No significant financial relationships to disclose.
Circulating endothelial cell (CEC) monitoring in metastatic colorectal cancer (mCRC) patients (pts) treated with first-line bevacizumab (BEV)-based combination regimens: Results of the randomized phase II FNCLCC-ACCORD 13/0503 trial
Authors: Farace F. , Mendiboure J. , Adenis A. , Boucher E. , Pierga J. , Conroy T. , Montoto-Grillot C. , Pignon J. , Ducreux M. , Malka D. ,   FNCLCC
Published: August 2020

4071 Background: There is no validated biomarker to predict the efficacy of BEV, an anti-VEGF monoclonal antibody. Rare cell subpopulations such as CEC are good candidates. Methods: Pts with mCRC, aged 18–75 yrs, ECOG performance status (PS) 0–2, and no prior palliative chemotherapy were randomized to either BEV (5 mg/kg) + FOLFIRI every 2 weeks (arm A, 12 cycles) or BEV (7,5 mg/kg) + XELIRI every 3 weeks (arm B, 8 cycles). BEV was continued until disease progression [PD]. The primary endpoint was crude 6-month progression-free survival (PFS) rate. In consenting pts, CEC (CD45-CD31+CD146+7- amino-actinomycin- cells) were measured at baseline (Day [D]1, before treatment), D8, and at the end of cycle 1 (D15 or 22) in 1-mL whole blood by four-color flow cytometry according to a method we established previously (J Immunol Methods 2008). Results were correlated to pts’ characteristics and primary endpoint (Wilcoxon's, Fisher's, and trend tests). Results: From 03/06 to 01/08, we enrolled 145 pts (male, 56%; median age, 61 yrs; PS 0–1, 91%; number of metastatic sites [1/2/>2], 45/48/8%). Pts with at least one CEC measurement (n=99; arm A, 51; arm B, 48) did not differ from the 46 other pts regarding sex, age, PS, and number of metastatic sites. Baseline CEC levels (n=97; median, 16/mL) were higher in PS 1–2 pts (n=42) than in PS 0 pts (n=55) (17 vs. 12/mL, p=0.02) (age, sex, number of metastatic sites: NS) and in pts with PD (n=17) than in pts with non- PD (n=80) at 6 months (30 vs. 15/mL, p=0.004). CEC levels were higher at the end of cycle 1 in the PD group (n=17) than in the non-PD group (n=74) (34 vs. 14/mL, p=0.01). The 6-month PFS rate varied from 0% to 32% in the 4 groups defined by baseline and end-of-cycle- 1 CEC values (cutoff: baseline median) (trend test, p=0.006) ( table ). Conclusions: Baseline and end-of-cycle-1 CEC levels may predict tumor control in patients with mCRC starting first-line BEV + chemotherapy. [Table: see text] [Table: see text]
The impact of young age on outcome in colon cancer
Authors: Truong C. , Kempton S. , Lum S. , Morgan J. W. , Wong J. H. , Roy-Chowdhury S. 
Published: August 2020

4075 Background: The early age of diagnosis (<40 years) of colon cancer (CC) is generally considered to be associated with a particularly grave prognosis. Our objective was to determine the prognostic relevance of young age on outcome in CC. Methods: Retrospective cohort study from Region 5 of the California Cancer Registry (R5 CCR). Survival by Kaplan- Meier with significance assessed by log-rank test, T-test and Chi Square where appropriate. Results: Between January 1,1994 and December 31, 2003 10,730 patients with CC were diagnosed in R5 CCR. The patients ranged in age from 18–103 years (mean 71.1 years). Two hundred fourteen patients (2%) were 40 years of age or younger. The mean age of young patients was 34.6 years (range 18–40) and for old patients 71.3 years (range 41–103). The mean number of nodes examined were 18.5 in the young CC patient and 18.4 in the remainder of CC patients. There was no significant difference in the anatomic sub-site of the primary between younger and older CC patients (p=0.43). Young patients presented with more advanced primary tumors (T4 18.7% vs. 11.6%, p=0.03), more frequently with more extensive nodal involvement (N+ (54.4% vs. 40.2%, p<0.0001), and more frequently with distant metastatic disease (M1 25.7% vs. 18.3%, p=0.005). Despite these adverse characteristics, young patients had a significantly better disease specific survival (DSS) compared to their older counterparts (5 year survival 70.1% vs. 62.3%, p=0.02). Young patients had a suggestion of improved DSS compared to older patients in Stage I disease (5 yr DSS 96.0% vs. 90.5%, p=0.34) with more certain evidence of improved DSS in Stage II (5 yr DSS 94.8% vs. 79.9%, p=0.02), Stage III (5 yr DSS 73.4% vs. 57.2%, p=0.01) and most profoundly in Stage IV (5 yr DSS 20.1% vs. 0.08%, p=0.002). Conclusions: Despite adverse characteristics at diagnosis, young CC patients have a better DSS than their older counterparts. This is in contrast to the generally held opinion that young CC patients fare worse. This may reflect the ability of young CC patients to accept and tolerate more intense and aggressive therapies. No significant financial relationships to disclose.
Cetuximab plus FOLFIRI first line in patients (pts) with metastatic colorectal cancer (mCRC): A quality-of-life (QoL) analysis of the CRYSTAL trial
Authors: Folprecht G. , Nowacki M. , Lang I. , Cascinu S. , Shchepotin I. , Maurel J. , Rougier P. , Cunningham D. , Zubel A. , Van Cutsem E. 
Published: August 2020

4076 Background: Assessing QoL is important to evaluate the impact of treatment on pts with mCRC. The phase III CRYSTAL trial compared cetuximab plus FOLFIRI with FOLFIRI alone in the first-line treatment of patients with EGFR-expressing mCRC. Primary endpoint was progression-free survival (PFS); QoL was a secondary endpoint. Methods: Pts were randomised 1:1 to cetuximab (400 mg/m2 initial dose then 250 mg/m2/wk) plus FOLFIRI q2w (irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2400 mg/m2 over 46 h) (Group A, n=599) or FOLFIRI alone (Group B, n=599). QoL was assessed with the EORTC QLQ-C30 (v3.0) questionnaire. Pts were to complete the questionnaire at baseline, every 4 cycles, and at final tumor assessment. The primary QoL analysis focused on Global Health Status and Social Functioning scales and employed a pattern-mixture model that included the drop-out pattern. Descriptive statistics were provided for each multi-item scale considering QoL changes over time. Results: Risk of disease progression was significantly reduced by 15% (HR=0.85) in favor of Group A (p=0.0479); pts with KRAS wild-type (wt) tumors in Group A had a 32% (HR=0.68) reduced risk of progressing. Questionnaire completion compliance rates were similar between treatment groups. Pattern-mixture analyses showed no statistically significant differences between the two treatment groups for changes from baseline on the Global Health Status (p=0.29) and Social Functioning (p=0.39) scales. Comparing treatment groups in terms of QoL scores over time resulted in no statistically significant differences, apart from nausea/vomiting in favor of the cetuximab group at week 16 (10.2 vs 13.3; p=0.0129), week 32 (9.3 vs 12.5; p=0.0488) and week 40 (7.6 vs 12.5; p=0.0194). Conclusions: In pts with mCRC, cetuximab plus FOLFIRI first-line significantly prolongs PFS compared with FOLFIRI alone while preserving QoL. The PFS benefit is even more pronounced for pts with KRAS wt tumors. The EORTC QLQ-C30 Social Functioning scale was expected to reflect skin reactions related to cetuximab, but there was neither a clinically meaningful nor statistically significant difference between groups. [Table: see text]
Phase III study of standard triweekly versus dose-dense biweekly capecitabine (C) + oxaliplatin (O) + bevacizumab (B) as first-line treatment for metastatic colorectal cancer (mCRC): XELOX-A-DVS (dense versus standard): Interim analysis
Authors: Hurwitz H. , Patt Y. Z. , Henry D. , Garbo L. , Mitchell E. P. , Kohles J. , Spigel D. 
Published: August 2020

4078 Background: Every 3 week (Q3W) COB has been shown to be highly active and non-inferior to FOLFOX+B in first-line mCRC. Phase II data suggest that dose-dense every 2 week (Q2W) COB may be significantly more active and better tolerated than Q3W COB. Methods: XELOXA-DVS was a phase III, open-label study of 435 patients with chemonaive mCRC who met standard eligibility criteria. Patients were randomized to Q3W: C 850 mg/m2 BID d1–14 + O 130 mg/m2 d1 + B 7.5 mg/kg d1 or Q2W: C 1500 mg/m2 BID d1–7 + O 85 mg/m2 d1 + B 5 mg/kg d1 for up to 72 weeks. Complete surgical resection was allowed using pre-defined criteria. The primary endpoint, progression-free survival (PFS), was estimated using the Kaplan- Meier method, while the hazard ratio and 95% CI were estimated using Cox regression analysis, based on the intent-to-treat population. No formal statistical testing was conducted. Results: The median PFS was 8.4 months (Q2W) and 9.7 months (Q3W) (hazard ratio [HR]=0.84; 95% CI=0.62–1.13). The median PFS (on-treatment) was 9.1 months and 10.2 months, respectively (HR=0.81). Of the 72 and 73 patients with disease progression (DP), the median time to DP was 9.4 and 10.8 months, respectively (HR=0.86). The objective response rates were 21.7% vs 29.4%, respectively (HR=1.05). Patients in the Q2W vs Q3W group experienced higher rates of grade 3/4 diarrhea (29% vs 24%), hand-foot syndrome (12% vs 8%), and treatment discontinuation rates (40% vs 20%), respectively. Other grade 3/4 toxicities (>5%, Q2W vs Q3W) included fatigue (13% vs 13%), dehydration (12% vs 10%), nausea (8% vs 9%), peripheral neuropathy (5% vs 9%), anorexia (5% vs 7%), and abdominal pain (5% vs 7%). Conclusions: At the dose and schedule used, dose-dense Q2W COB was not superior to standard Q3W COB. These data further confirm the activity and tolerability of Q3W COB. The activity and tolerability of a lower C dose Q2W, with more aggressive dose reduction, combined with B and O or irinotecan is currently being evaluated (X-BIO). [Table: see text]
Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC)
Authors: Bullock K. E. , Hurwitz H. I. , Uronis H. E. , Morse M. A. , Blobe G. C. , Hsu S. D. , Zafar S. Y. , Nixon A. B. , Howard L. A. , Bendell J. C. 
Published: August 2020

4080 Background: For patients (pts) with mCRC, no standard therapy exists after progression on 5-FU, oxaliplatin, irinotecan, bevacizumab, and/or cetuximab/panitumumab. Preclinical data demonstrate combined VEGF and mTOR inhibition has greater anti-angiogenic and anti-tumor activity than either monotherapy. B inhibits VEGF; E inhibits mTOR. Phase I data in patients demonstrated B + E was safe and activity was seen in several pts with refractory mCRC. Methods: 25 pts with refractory mCRC were enrolled in an expanded cohort of B + E. Doses: B 10 mg/kg q2 wks; E 10 mg PO QD. Blood, skin, and tumor biopsies pre- and on-treatment were collected for markers of response and resistance. Results: At this time, 19 pts (10M: 9F) are evaluable for toxicity; 17 for efficacy. Median age 57 years (range 35–78). Median number prior regimens 3. All pts had prior B exposure; 17 pts had progressive disease on prior B-based therapy. There was one Grade (Gr) 4 adverse event (AE) of hypokalemia. Grade 3 AE related to treatment were bowel perforation/fistula, (n=2), hyperglycemia (3), hypokalemia (3), hypertension (2), fatigue (1), alk phos elevation (1; lab only), hypoalbuminemia (1), and volume depletion (1). Other events of interest were: Gr1–2 mucositis (n=10), Gr1 hyperlipidemia (11). Of 17 pts evaluable for response, 4 pts had SD as best response (median 24 wks, range 17–31+ wks); there were 3 minor responses in pts who had progressed on B (median 16 wks, range 16–27 wks). No CR or PR were seen. Biomarker data is pending. Conclusions: B+E has activity in refractory mCRC in pts who had progressed on a B-based regimen, suggesting B+E may overcome resistance to B. Patient accrual is continuing and updated data will be presented. [Table: see text]
Randomized phase II study of perifosine in combination with capecitabine versus capecitabine alone in patients with second- or third-line metastatic colon cancer
Authors: Vukelja S. , Richards D. , Campos L. T. , Bedell C. , Hagenstad C. , Hyman W. , Letzer J. , Gardner L. , Sportelli P. , Nemunaitis J. 
Published: August 2020

4081 Background: Perifosine (Peri), a synthetic alkylphospholipid, inhibits or modifies a number of different signal transduction pathways (AKT, MAPK and JNK). Peri as a single agent or in combination with other cytotoxic agents, has shown clinical benefit with a manageable safety profile. In a phase I solid tumor trial, Peri was safely combined with capecitabine (Cap) and demonstrated interesting activity in patients (pts) with metastatic colorectal cancer (mCRC), with one patient progression-free for 49 weeks (wks). To assess the true effect of Peri, a phase II was initiated as an exploratory randomized double-blind, placebo controlled study where mCRC pts received Cap in combination with Peri or placebo. Methods: Pts with 2nd or 3rd line mCRC, not previously treated with single agent Cap. ECOG PS 0–1, normal organ/marrow function required. Dose for Cap was 825 mg/m2 BID d 1–14 q 3 weeks. Dose for Peri or placebo was 50 mg qd. Primary outcome analyses included median time to progression (TTP) and response rate (CR+PR). Results: 37 pts have been randomized. Median age 68 (range 32–83) and 57% were male. Median prior Rx was 2 (range 1 - 5). For the analyses, 25 pts were unblinded (12 too early) with 22/25 pts evaluable for response (2 pts off for toxicity at d 14, 46 and 1 patient off at d 4 for other disease; all 3 pts were on Cap + placebo). Results in table below. The log-rank p-value comparing active to placebo for TTP is 0.01. As of 12/08, all unblinded pts are off treatment and 11/12 that were too early remain on treatment with enrollment ongoing. Most frequent (>5%) grade 3 /4 adverse events for Cap + Peri was hand/foot syndrome (16%) and anemia (8%); for Cap + placebo was fatigue (8%). Conclusions: Perifosine in combination with capecitabine was well tolerated, clinically active and more than doubled median TTP over capecitabine alone in pts with advanced, metastatic CRC. [Table: see text] [Table: see text]
A phase I clinical trial of vorinostat in combination with sFULV2 in patients with refractory solid tumors
Authors: Fakih M. G. , Pendyala L. , Egorin M. J. , Fetterly G. , Espinoza-Delgado I. , Ross M. , Phelan J. , Kramer Z. , Yirinec B. , Diasio R. 
Published: August 2020

4083 Background: Thymidylate synthase (TS) over-expression is associated with 5-FU resistance. Pre-clinical studies demonstrate that vorinostat down-regulates intra-tumor TS in a dose-dependent fashion and augments 5-FU antitumor activity in xenograft models. We conducted a phase I clinical trial of an intermittent schedule of QD x 3 vorinostat in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) in patients (pts) with refractory solid tumors. Methods: Vorinostat was escalated in a standard 3 x 3 design in combination with a fixed dose of 5-FU and LV (simplified de Gramont regimen, sFULV2). Vorinostat was given QD x 3 on an every-2-week cycle. sFULV2 started on day 2 of vorinostat and consisted of leucovorin 400 mg/m2 i.v. over 2 hrs followed by 5-FU 400 mg/m2 bolus and 5-FU 2400 mg/m2 over 46 hrs. Results: 24 pts were enrolled: Male/Female: 11/13; ECOG 0/1: 6/18; Age: median 60 (range 42–77) yrs. 21 pts had colorectal cancer (CRC), 1 had gastric, 1 had esophageal, and 1 had anal cancer. Vorinostat dose-levels (DL) were 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1700 mg, and 2000 mg. Dose-limiting toxicities (DLT), consisting of fatigue and hand-and-foot syndrome (H&F), were seen in 2 of 3 pts at the 2000 mg DL. None of the 6 pts at the 1700 mg DL had a DLT. Cycle 1 grade 3/4 toxicities consisted of thrombocytopenia, GI bleeding, fatigue, and H&F in 2 pts at the 2000 mg DL and a non-DLT G3 diarrhea (lasted <24 hrs) in 1 pt at the 1700 mg DL. Grade 2 nausea, fatigue, and anorexia were common; especially at DL ≥ 1700 mg. Antitumor activity was noted in pts with CRC despite prior refractoriness to 5-FU and failure to oxaliplatin, irinotecan, and cetuximab in all pts. 12/21 CRC pts had a confirmed SD (11) or PR (1). CRC pts had a median PFS of 4 months, a ≥ 6 months PFS rate of 43%, and a ≥ 8 months PFS rate of 33%. Conclusions: The maximum tolerated dose (MTD) of vorinostat in combination with sFULV2 is 1700 mg PO QD x 3 every 2 weeks. This combination is associated with considerable activity in pts with 5-FU-refractory CRC and warrants further investigation. An expanded MTD cohort is accruing to investigate 5-FU-vorinostat PK interaction and intra-tumor TS down-regulation. (This work was supported by a grant from CTEP and the ACS.) No significant financial relationships to disclose.