bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter phase I study of intravenous administration of reolysin in combination with irinotecan/fluorouracil/leucovorin (FOLFIRI) in patients (pts) with oxaliplatin-refractory/intolerant KRAS-mutant metastatic colorectal cancer (mCRC).
Authors: Ocean Allyson J. , Bekaii-Saab Tanios S. , Chaudhary Imran , Palmer Romae , Christos Paul J. , Mercado Alice , Florendo Erika O. , Rosales Veronica A. , Ruggiero Joseph T. , Popa Elizabeta C. , Wilson Melissa , Ghalib Mohammad Haroon , Hou Yijuan , Shah Umang , Rajdev Lakshmi , Elrafei Tarek , Gill George M. , Coffey Matthew C. , Shah Manish A. , Goel Sanjay 
Published: February 2017

450 Background: Reolysin (reovirus serotype 3) contains a naturally occurring, ubiquitous, non-enveloped human dearing strain reovirus. Reovirus replicates in KRAS-mutant cells resulting in cell lysis. In phase I evaluation, CRC pts received single agent Reolysin with tumor stabilization and CEA response without significant toxicity. Reolysin and irinotecan (IRI) are synergistic in KRAS-mutant preclinical CRC models, providing rationale for this phase I study. Methods: This was a phase I dose escalation study of FOLFIRI + Reolysin. Eligible pts were >18 yrs with histologically confirmed KRAS-mutant mCRC, measurable disease, ECOG PS 0-1, <3 metastatic regimens, and adequate organ function. Standard FOLFIRI was administered with escalating Reolysin doses (range 1x1010 TCID50 to 3x1010 TCID50) in cohorts of 3-6 pts. Reolysin was given IV over 1 hr days 1-5 every 28d (1 cycle). Primary objectives were dose-limiting toxicity (DLT) to determine MTD and pharmacokinetics. Secondary endpoints were antitumor activity, response rate, progression-free and overall survival (PFS and OS). Results: 21 pts enrolled; median age 62 (range 39-77); 5 M; 16 F; FOLFIRI-naïve: 9/21 pts. 2 pts had DLTs in cycle 1 at the highest dose of 180 mg/m2 of IRI. Common (>10%) grade 3-4 toxicity include: neutropenia (n=11), anemia (n=4), and thrombocytopenia (n=3). One patient died of acute renal failure. The DLT is neutropenia. The recommended phase II dose is IRI 150 mg/m2 and Reolysin at 3x1010 TCID50 on days 1-5, q 28 days. 18 pts evaluable for response: PR (1pt; 5%), SD (9 pts; 50%), PD (8pts; 44%). 3 pts taken off study before evaluation. Median PFS: FOLFIRI-naïve pts = 7.4 mo. (95% CI = 1.9 mo., 12.9 mo.); Median PFS FOLFIRI non-naïve pts was not reached; overall median PFS = 7.4 mo. (95% CI = 0.6 mo., 14.1 mo.) Conclusions: The combination of Reolysin and FOLFIRI in pts with KRAS-mutant mCRC was safe, well tolerated and resulted in disease control in the majority of pts, including pts who previously progressed on IRI. We are encouraged by this activity and safety profile, and are planning additional studies. Clinical trial information: NCT01274624.
SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).
Authors: Hecht J. Randolph , Cohn Allen Lee , Dakhil Shaker R. , Saleh Mansoor N. , Piperdi Bilal , Cline-Burkhardt Vivian Jean M. , Tian Ying , Go William Y. 
Published: February 2017

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]
Induction treatment in first-line with chemotherapy + bevacizumab (bev) in metastatic colorectal cancer: Results from the gercor-DREAM phase III study.
Authors: Tournigand Christophe , Scheithauer Werner , Samson Benoit , Lledo Gérard , Viret Frédéric , Andre Thierry , Ramée Jean François , Tubiana-Mathieu Nicole , Dauba Jérôme , Dupuis Olivier , Rinaldi Yves , Mabro May , Aucoin Nathalie , Khalil Ahmed , Latreille Jean , Louvet Christophe , Brusquant David , Bonnetain Franck , Chibaudel Benoist , De Gramont Aimery 
Published: February 2017

457 Background: the DREAM study compares a maintenance therapy with bevacizumab (bev) alone or with the erlotinib after a bev-based induction therapy with FOLFOX, or biweekly XELOX or FOLFIRI. Efficacy of the induction treatment is reported here. Methods: Patients (pts) with previously untreated metastatic colorectal cancer received one of the following regimen (investigator’s choice): mFOLFOX7-bev, biweekly mXELOX-bev or FOLFIRI-bev. Oxaliplatin was administered no more than 6 cycles. In the 1st cohort, pts received 3 months (m) of FOLFOX-bev or mXELOX-bev before randomization. In the 2nd cohort, pts received 3m of FOLFOX-bev or mXELOX-bev then 3 m of fluoropyrimidine-bev, or 6 m of FOLFIRI-bev before randomization. Pts with disease control were then randomized between bev alone or with erlotinib until progression. Results: FOLFOX-bev was administered in 424 pts, mXELOX-bev in 203 pts and FOLFIRI-bev in 67 pts. Pts characteristics for the whole population are: median age 63 yrs (26-80), male/female 59.8%/40.2%, synchronous mets/metachronous 82.6%/17.4%, PS 0/1/2 58%/39%/3%, LDH>UNL 53%, platelets >400000/mm3 27%. Patients received a median nb of 6 cycles of oxaliplatin for FOLFOX-bev and mXELOX-bev, and a median nb of 12 cycles of irinotecan with FOLFIRI-bev. Response rates are respectively 48%, 50% and 63%. Median PFS are respectively 8.61m, 8.97m and 9m. Severe toxicity profiles (grade 3-4) appear to be different according to the schedule : more neutropenia and diarrhea with FOLFIRI-bev, HFS and diarrhea with mXELOX-bev and neuropathy with FOLFOX-bev. Conclusions: Modified biweekly XELOX-bev provides similar efficacy results with FOLFOX-bev, and FOLFIRI-bev as induction therapy in first-line. Clinical trial information: NCT00265824.
Time course of regorafenib-associated adverse events in the phase III CORRECT study.
Authors: Grothey Axel , Van Cutsem Eric , Sobrero Alberto F. , Siena Salvatore , Falcone Alfredo , Ychou Marc , Humblet Yves , Bouche Olivier , Mineur Laurent , Barone Carlo , Adenis Antoine , Tabernero Josep , Yoshino Takayuki , Lenz Heinz-Josef , Goldberg Richard M. , Sargent Daniel J. , Cihon Frank , Wagner Andrea , Laurent Dirk , Cupit Lisa 
Published: February 2017

467 Background: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Methods: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Results: The safety population comprised 753 patients (pts): REG n=500; placebo n=253. The mean treatment duration was 12.1 ± 9.7 weeks in the REG group and 7.8 ± 5.2 weeks in the placebo group. Treatment-emergent AEs occurred at any grade in 99.6% of REG pts and 96.8% of placebo pts, at grade 1/2 in 21.6% and 47.8%, respectively, at grade 3 in 56.0% and 26.5%, respectively, and at grade 4/5 in 22.0% and 22.5%, respectively. AEs occurring in ≥10% more REG than placebo pts were fatigue, hand–foot skin reaction (HFSR), anorexia, diarrhea, weight loss, voice changes, hypertension, rash/desquamation, oral mucositis, fever, hyperbilirubinemia, low platelet count. The most frequent AEs deemed to be regorafenib related were HFSR, fatigue, diarrhea, hypertension, and rash/desquamation. The frequency of these AEs over time is shown in the Table. The incidence of HFSR, fatigue, hypertension, and rash/desquamation peaked in cycle 1 and tapered to a relatively stable lower incidence over later cycles. The incidence of diarrhea remained relatively constant throughout treatment. AEs led to dose modification in 66.6% of pts in the REG group and 22.5% in the placebo group. Data on dose intensity across treatment cycles will be presented. Conclusions: In the CORRECT trial, the incidences of the most common AEs in the REG group peaked early during treatment. There appeared to be no evidence for cumulative toxicity of REG. Clinical trial information: NCT01103323. [Table: see text]
A phase II multicenter study of metastasectomy for intra- and extra-hepatic metastases from colorectal cancer.
Authors: Wei Alice Chia-chi , Coburn Natalie G. , Moulton Carol-anne , Cleary Sean P , Law Calvin , Greig Paul David , Gallinger Steven 
Published: February 2017

482 Background: Metastasectomy for liver limited metastases from colorectal cancer (CRC) provides excellent 5-year overall survival (OS) rates. The presence of extra-hepatic metastases (EHM) has traditionally been a contraindication to surgery. On this basis, as many as 80% of patients are deemed ineligible for liver resection. Due to the improved safety of hepatic surgery, there is a growing interest in multi-site metastasectomy for patients with intra-hepatic and extra-hepatic metastases (IHM, and EHM). The objective of this study was to evaluate the results of complete metastasectomy for patients with IHM and EHM from CRC. Methods: A phase II study of metastasectomy for both IHM and EHM from CRC was conducted at 2 high volume hepato-pancreato-biliary (HPB) centers. Eligible patients with any number resectable IHM and up to 3 foci of EHM, resectable with RO intent were offered metastasectomy. Clinical and survival data was analyzed using standard statistical methods. Results: Twenty-five patients were enrolled with a median age of 57 (32-84) years; 14/25 (56%) patients presented with synchronous disease. The median number of IHM, EHM and combined sites were 2, 1 and 3, respectively. The lung was the most common site of EHM (12/25, 48%). Protocol surgery was completed in 18/25 (72%) including 11/25 (44%) planned sequential resections. Perioperative morbidity and mortality was 11/25 (44%) and 1/25 (4%), respectively. The median disease free survival was 6 months. The median OS from the time of CRC diagnosis, first metastasectomy and completion metastasectomy was 47, 27 and 23 months, respectively. Conclusions: Complete metastasectomy of multi-site CRC is feasible and safe. However, disease will recur in the majority of patients. The impact to aggressive multi-site metastasectomy is modest but may provide OS benefit in selected patients.
Adjuvant treatment and outcomes in patients with stage III colon cancer (CC) who do not fit clinical trial eligibility criteria (CTEC).
Authors: Rasool Javaheri Khodadad , Kennecke Hagen F. , Renouf Daniel John , Lim Howard John , Hsu Tina , Speers Caroline , Goktepe Ozge , Cheung Winson Y. 
Published: February 2017

486 Background: Trials have strict inclusion and exclusion criteria to maintain internal validity. However, study findings are often applied to pts in clinical practice who do not satisfy all of the CTEC. Whether these pts benefit from treatment is unclear. Our objectives were 1) to characterize cancer-specific (CSS) and overall survival (OS) in a population-based cohort of trial-eligible (TE) and trial-ineligible (TI) pts receiving adjuvant chemotherapy (CT) and 2) to compare their outcomes with those not treated with CT. Methods: Pts diagnosed with stage III CC between 2006 and 2008, referred to 1 of 5 regional cancer centers in British Columbia, and evaluated for possible adjuvant CT within 12 weeks of curative surgery were reviewed. Pts were defined as TE if aged 18 to 79 years, ECOG 0 to 1, CEA <10 ng/ml, had not received prior CT or radiation, and had adequate blood counts, cardiac, liver, and kidney function. All other pts were considered TI. Using Kaplan-Meier and Cox regression analyses, we compared outcomes between TE and TI pts who received CT vs. those who did not. Results: A total of 821 pts were identified: median age was 68 years, 52% were men, 85% were ECOG 0 to1, and 71% received adjuvant CT. Among pts treated with CT, 405 (70%) were TE and 177 (30%) were TI. Compared to TI pts, those who were TE were younger (p<0.01) and more likely to receive FOLFOX than capecitabine (65 vs. 46%, p<0.01). CSS and OS were significantly different among pts who were TE, TI, and those who did not receive CT (p<0.01) (Table). In multivariate analyses that adjusted for confounders, both TI pts and those not treated with CT had worse prognoses than TE pts (HR for CC deaths 1.32, 95%CI 0.86-2.02 and 2.77, 95%CI 1.92-3.99, respectively, p trend <0.01; HR for all deaths 1.24, 95%CI 0.85-1.80 and 2.95, 95%CI 2.17-4.00, respectively, p trend <0.01). Conclusions: A considerable number of stage III CC pts who did not fit CTEC were treated with adjuvant CT. While outcomes in the TI group were worse than those in the TE group, CSS and OS were still better than the subset that did not receive any CT. [Table: see text]
Patterns of recurrence after resection of rectal gastrointestinal stromal tumors and the effect of adjuvant therapy.
Authors: Yasui Masayoshi , Mori Masaki , Takahashi Tsuyoshi , Nakashima Yasuo , Dousei Tsutomu , Yamashita Yoshito , Fujita Junya , Hiramatsu Masako , Kawabata Ryohei , Nakai Koji , Nakai Takuya , Nishida Toshirou , Noguchi Miki , Orita Hajime , Shono Yoshiharu , Souma Yoshihito , Takagi Masakazu , Ueda Shugo , Yamamoto Kazuyoshi , Tsujinaka Toshimasa ,   Kinki GIST Study Group
Published: February 2017

531 Background: Since gastrointestinal stromal tumors (GISTs) of the rectum are rare, clinical features and treatment outcome have not been well documented. Methods: Data from patients with rectal GIST diagnosed and primarily treated between 2003-2007 at 17 institutions in Japan were collected and analyzed on clinical characteristics, pathologic features and recurrence patterns. Results: Twenty-five patients (11 men and 14 women) with rectal GISTs were collected. Median age was 67years old. Pathological examinations disclosed that the median number of mitoses and the size of tumors were 4 counts/50HPF and 4.5cm, respectively. By the Miettinen criteria, 44 percent (n = 11) were classified as high-risk, 32 percent (n = 8) as low-risk and 16 percent (n = 4) as none-risk gastrointestinal stromal tumors. Sixty-three percent (7/11) of patients with high-risk GISTs had developed recurrence. None of patients (n = 12) with low or none-risk gastrointestinal stromal tumors have recurred after a median follow-up of 1699 (range, 135-3871) days. 85 percent (6/7) of recurrent patients showed loco-regional recurrence. Twelve patients with rectal GISTs received local excision and thirteen patients received extended resection (abdominoperineal resection or low anterior resection). Loco-regional recurrence rate following local excision was 25% (3/12), which was similar with that of extended resection (23%, 3/13).7 patients received neoadjuvant and/or adjuvant imatinib. Only one patient of 7 patients who received perioperative imatinib treatment developed recurrence. Conclusions: Loco-regional recurrence was the most predominant pattern of recurrence after surgical resection of rectal GISTs. The Miettinen criteria were useful to differentiate the high risk group. Recurrence rate was lower in patients treated with perioperative imatinib. Rectal GIST may be optimally managed by perioperative multimodal treatment instead of extending surgical resection.
Thrombotic events in patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab.
Authors: Al-Shamsi Humaid O. , Anjum Mahraz , Al Farsi Abdulaziz , Shen Hua , Linkins Lori-Ann , Cook Richard J. , Major Pierre 
Published: February 2017

540 Background: The rate of venous thromboembolism (VTE) in (mCRC) with bevacizumab was reported in a meta-analysis as 19.1%. We estimated and compared the rate of VTE among mCRC patients receiving FOLFIRI and bevacizumab with patients receiving FOLFIRI without bevacizumab. Methods: We conducted a retrospective cohort study assessing the rate of VTE in a group of 450 mCRC patients seen consecutively at the Juravinski Cancer Center. Patients were classified according to their treatment: chemotherapy plus bevacizumab group (n=261) and control group (n=189) who received only FOLFIRI during the years 2004 to 2012. Demographic, pathologic and treatment data were abstracted. Multivariate analysis was used to adjust for the effect potential confounding variables associated with treatment and VTE and to assess the effect of these variables risk of VTEs in this population. The primary end point was the occurrence of a VTE. Secondary analyses involved classifying site of VTE. Results: The percentage of male, mean age and mean BMI were 64.8%, 60.1 years and 27.2 for the bevacizumab group and 61.9%, 63.69 years and 27.6 are for the control group. The crude incidence of VTEs was 13.1% in bevacizumab and 10.5% in the control groups (p = NS). Multivariate analysis controlled for age, BMI, gender, malignancy, metastatic disease and line of treatment did not suggest a significant increase in risk of VTE associated with bevacizumab (OR=0.83 95% CI: 0.40, 1.70; p=0.602). The only significant factor for thrombosis in bevacizumab group was BMI (OR=1.05; 95% CI: 1.01, 1.10; p=0.016). Other risk factors such as previous VTE, stroke, smoking, and hypertension were not statistically significant when assessed through a composite covariate. For anatomical location of VTEs, see the Table. Conclusions:The rate of VTEs overall was lower in our sample than has been reported in previous studies. We excluded upper limb DVTs associated with central lines which may explain the lower VTEs overall. The incidence of VTEs was not significantly different between the bevacizumab and the control groups. bevacizumab was not associated with increase risk of VTES . This support the safety of bevacizumab in regards to VTEs risk in this population. The incidence of venous thromboembolism (VTE) in FOLFIRI with and without bevacizumab. [Table: see text]
Randomized comparisons of IL-6 and lean body mass between open versus laparoscopic distal gastrectomy for gastric cancer.
Authors: Yoshikawa Takaki , Hayashi Tsutomu , Aoyama Toru , Shirai Junya , Fujikawa Hirohito , Ogata Takashi , Cho Haruhiko , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Tsuburaya Akira 
Published: February 2017

55 Background: Laparoscopic distal gastrectomy (LA) for gastric cancer may reduce breakdown of the muscle protein due to less surgical stress, compared with open surgery (OP). Methods: This study was performed as an exploratory analysis of a phase III trial comparing OP and LA for stage I gastric cancer in KCCH by limiting the period between May and Dec of 2011. IL-6 was measured before and 12 hours after surgery. Prealbumin and body composition were examined before and 7 days after surgery. %LBM was defined as percentile of LBM at 7 days to LBM before surgery. Values were expressed as median and range. Results: Twenty-seven patients were randomized to OP in 14 and LA in 13. Baseline: Body weight, LBM, prealbumin, and IL-6 were similar between both. Surgery and pathology D1/D1+/D2 lymph node dissections were 0/9/5 in OP and 0/9/4 in LA (p=0.785). Blood loss (g, range) and operation time (minutes, range) were 160 (50-475) and 174.5 (85-276) in OP, respectively, and 40 (5-270) and 267 (168-360) in LA, respectively, which were both significantly different (p=0.009 and 0005, respectively). Pathological T and N were similar between both. Morbidity and mortality: Any complications > grade 2 defined by Clavien-Dindo classification were 2 (14.3%) including grade 3B anastomotic stenosis and 3A pancreatic fistula in OP and 1 (7.7%) grade 2 transient ischemic attack in LA (p=0.586). Measurements: IL-6 (pg/ml, range) after 12 hours was 36.3 (14.4-405.0) in OP and 53.3 (24.1-217.0) in LA (p=1.000). Prealubumin (mg/dl, range) was 17.3 (11.7-23.7) in OP and 17.8 (10.5-28.7) in LA (p=0.680). %LBM (range) was 96.9 (93-101) in OP and 96.5 (93-100) in LA (p=1.000). When excluding the patients who developed morbidity > grade 2, IL-6 (range) was 32.1 (14.4-405.0) in OP and 49.5 (24.1-217.0) in LA (p=0.356). Prealubumin (mg/dl, range) was 17.7 (13.7-23.7) in OP and 17.8 (10.5-28.7) in LA (p=0.729). %LBM (range) was 97.1 (93-101) in OP and 97.2 (94-100) in LA (p=1.000). Conclusions: Laparoscopic approach has no impact on surgical stress and breakdown of the muscle protein after distal gastrectomy.