bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab plus FOLFOX7 as first line treatment in patients with advanced colorectal cancer
Authors: Oukkal M. , Kara F. , Difi S. , Bouzidi D. , Bentabak K. , Graba A. , Smail N. , Ait Kaci N. , Baba Ahmed R. , Bouzid K. 
Published: August 2020

e15092 Background: Bevacizumab a monoclonal antibody against vascular endothelial growth factor (VEGF) has shown in combination with chemotherapy a significant survival improvement in pts with advanced colorectal cancer (F. Kabbinavar JCO 2005 and H. Hurwitz NEJM 2004). In this study we investigated the safety and the efficacy of the addition of bevacizumab to FOLFOX7 regimen in pts with metastatic colorectal cancer. Methods: Inclusion criteria: Histological proven colorectal carcinoma, measurable disease at time of inclusion, no prior chemotherapy (adjuvant chemotherapy allowed), no CNS metastasis, no peripheral neuropathy, no other serious concomitant illness, ECOG PS ≤ 2, Urine dipstick of proteinuria <2+, adequate renal and liver function, good bone marrow reserve and informed consent. Pts received bimonthly Oxaliplatin 130 mg/m2 D1, Folinic acid 400 mg/m2 D1, Fluorouracil 2400 mg/m2 46 hours continuous infusion and Bevacizumab 5mg/kg D3 Results: From April 2005 to June 2007, 47 pts (M/F = 28/19, colon/rectum = 28/19) were enrolled in the study. Median age is 52,7 years old (32–74). They received 452 cycles, median=7 range (1–18). All pts were evaluable for toxicity and survival and 46 for responses. Complete response (CR) was achieved in 3 pts (6.6%), partial response (PR) in 28 pts (60.8%), stable disease in 4 pts (8.7%) and progressive disease in 11 pts (24%). The overall response rate (ORR=CR+PR) is 67.3%. Severe toxicity (CTC/NCI ¾ Grade) related to chemotherapy was neuropathy 5.3%, neutropenia 8.4%, anaemia 3.3%, thrombocytopenia 1.8%, vomiting 8.2%, diarrhoea 2.9%, stomatis 4.9% and allergy 0.7%. Toxicity related to Bevacizumab was bleeding CTCNCI grade 1 and 2 in 40.8%, hypertension grade 1 qnd 2 in 3.7% qnd grqde 3 in 0.2. proteinuria grade and 2 in 13.7%. 1 case of phlebitis and 1 case of Bevacizumab allergy Conclusions: Bevacizumab and FOLFOX7 combination is a promising treatment with high efficacy and safety profile for pts with advanced colorectal cancer No significant financial relationships to disclose.
Neoadjuvant chemoradiotherapy for locally advanced low-lying rectal cancer
Authors: Yu B. , Zhang M. , Wu W. , Chen L. , Peng L. , Bian G. , Fu J. , Fei C. 
Published: August 2020

e15095 Objective: The aim of this trial was to explore the possibility of further improvement of efficacy in neoadjuvant chemoradiation for the treatment of locally advanced low-lying rectal cancer and the management of patients with clinical complete regression. Methods: 192 cases with locally advanced low-lying rectal cancer (T3/T4 or N+) received preoperative radiotherapy comprising 40–46 Gy/20–23 fractions and concomitant oral capecitabine 625 mg/m2 bid for 10 weeks prior to surgery. Curative resection with TME was carried out 6 weeks after the end of radiation. Results: Patients (pts) were recruited from May 2001 through August 2007. Overall, 117 pts (60.9%) experienced adverse events but only 2 suffered from grade 3 hand-foot syndrome. 17 pts (8.9%) had clinical complete tumor regression without surgery, 175 pts underwent curative resection including of 134 pts with low anterior resection (LAR), 32 pts with ultra-low anterior resection with Parks’ coloanal anastomosis and among them 6 pts with diverting temporary colostomy and 9 pts with APR. Sphincter preservation was achieved in 95.3%. Pathologically, 24 pts (12.5%) showed CR together with 17 pts with clinical CR; the overall CR rate was 21.4%. According to the pathological staging: T0N0 41 cases, T2N0 43 cases, T3N0 77 cases, T4N0 5 cases, T2N1 11 cases, T3N1 13 cases, T4N0 5 cases, and T4N1 2 cases; in semiquantitative Dworak's tumor regression grade, TRG0 8 pts,TRG1 32, TRG2 28,TRG3 83 and TRG4 41 with an overall tumor downstaging of 79.2%. There were no operative deaths, 5 pts suffered from rectovaginal fistulas and 4 anastomotic leakages with an overall anastomotic leakage rate of 5.1% (9/175) and all recovered without further events. All patients have been followed up for a median of 46 months (range 12–87). During the time, 11 pts had lung metastases, 6 liver metastases and 7 had local recurrences. The 3-year disease-free survival was 86.6% and overall survival was 92.6%. Conclusions: Neoadjuvant chemoradiotherapy has high efficacy resulting in tumor down-staging, increased resectability and sphincter preservation, and a reduction in local recurrences. Meanwhile those patients with clinical complete response can be followed up closely and safely without surgery. No significant financial relationships to disclose.
Phase II trial comparing folinic acid, fluorouracil, and gemcitabine (FFG) and FOLFOX4 regimens with added bevacizumab (B) in metastatic colorectal cancer (mCRC)
Authors: Madajewicz S. , Waterhouse D. M. , Ritch P. , Khan M. , Higby D. , Leichman C. G. , Malik S. K. , Hentschel P. , Zhao L. , Nicol S. J. 
Published: August 2020

e15098 Background: FOLFOX4 is a standard chemotherapy for mCRC. FFG has shown substantial activity in mCRC. This trial compared the safety and efficacy of FFG and FOLFOX4 regimens in patients (pts) with mCRC. B was added to each arm after FDA approval in 2004 as first-line treatment of mCRC. Methods: Pts with mCRC, chemonaïve except for adjuvant treatment, were randomized to two treatment arms: FFG given weekly for 6 weeks of an 8-week cycle; FOLFOX4 had a 2-week cycle. Pts in both groups received B at 5 mg/kg every 2 weeks. Treatment continued until disease progression. Planned enrollment was 150 pts. Primary endpoint was overall response rate (ORR); secondary endpoints included toxicity, overall survival (OS), and time to progression (TTP). Response was assessed by RECIST. Post-hoc analysis of disease control rate (DCR) was added. Results: Forty-two pts (18 pts given B) were randomized to each arm. Thirty-one cycles of FFG and 248 cycles of FOLFOX4 were delivered. FFG produced greater myelosuppression than FOLFOX4. Two cases each of MI and DVT were observed in the FOLFOX4(B) subgroup; one pt had DVT with FFG alone. The incidence of gastrointestinal hemorrhage was low and similar for FFG and FOLFOX4. Peripheral neuropathy was highest in the FOLFOX4(B) subgroup. ORR and DCR were significantly greater for FOLFOX4(B) than for FFG(B). Median TTP and OS were not statistically different for FFG and FOLFOX4 groups. The trial was stopped due to low enrollment; planned statistical power was not achieved. Conclusions: FFG and FOLFOX4 regimens were generally well tolerated, with greater neuropathy in FOLFOX4 and greater myelosuppression in FFG. ORR was greatest in the FOLFOX4(B) subgroup. TTP and OS results comparing FFG and FOLFOX4 groups were inconclusive due to low enrollment. Rapid changes in mCRC “standard of care” during this trial may have constrained pt accrual. [Table: see text] [Table: see text]
Long-term supportive treatment with fermented mistletoe (viscum album L.) extract in primary nonmetastatic colorectal cancer: Best time to start with for optimal effectiveness
Authors: Matthes H. , Friedel W. E. , Bock P. R. 
Published: August 2020

e15099 Background: Safety and efficacy of fermented mistletoe extract (Iscador, ISC) in supportive care of post-surgical patients with primary colorectal cancer as compared to a parallel control group without ISC. Question: Is supportive ISC most effective when started before, during, or after radio- and/or chemotherapy? Methods: In a comparative, multicenter, non-interventional cohort study with parallel groups ISC was applied additionally to conventional adjuvant chemo- and/or radiotherapy (conv-th). The control group was treated with conv-th only. Unselected, standardized, anonymized data from medical records (1993–2002) meeting the eligibility criteria were followed until last visit or death. The pre-specified endpoints were the incidence of adverse drug reactions (ADR) caused by conv-th, and disease-free survival (DFS) in relation to start of ISC therapy before, during or after conv-th. All endpoints were adjusted to confounders. Results: 804 eligible patients (429 ISC and 375 control) from 26 centers were evaluated. ISC started mostly during conv-th (72.9%), and sometimes before (9.0%) or after (18.1%) conv-th. ISC dose was escalated from 0.01mg to 20mg as s.c. injection, 2–3 times weekly. The median follow-up time was 58 (ISC) vs. 51 months and median ISC duration was 52 months. The adjusted relative ADR risk was significantly lower in the ISC groups as compared to control: odds ratio, OR (95% CI) = 0.46 (0.28–0.77), p=0.003. The best results were found in patients where ISC started in parallel to conv-th. Analysis of DFS in the ISC subgroups is presently ongoing. ISC was well tolerated in all subgroups. Conclusions: The results show reliable safety and clinically relevant beneficial effects of ISC treatment, at best if applied in parallel to conv-th. [Table: see text]
The role of contrast-enhanced ultrasound in detection of liver metastases from colorectal cancer: A prospective monocentric study
Authors: Mucciarini C. , Bellentani S. , Razzini G. , Bernardini I. , Artioli F. , Iop A. , Blanzieri S. 
Published: August 2020

e15105 Background: Up to 15–25% of patients with colorectal cancer (CRC) will develop metacronous liver metastases during the follow up. The management and prognosis of these patients depend heavily on the early detection of metastases. The most effective surveillance strategy has not yet being extablished. The introduction of second generation ultrasound contrast agents have improved the ability of contrast-enhanced ultrasound (CEUS) in detecting and characterizing liver lesions, showing that its accuracy is comparable to that of spiral CT and MRI with a liver contrast agent, with a cost and a time saving. We tested the sensitivity and specificity of CEUS in detecting liver metastases compared with the standard imaging modalities used in the follow up of CRC. Methods: We conducted a prospective study considering all patients with a diagnosis of CRC in high risk stage II, stage III or with a previous metastasectomy of the liver. In order to detect possible metastases, the patients were followed with a follow-up schedule including a six-monthly ultrasonography alternated to an annual CT, and a six-monthly CEUS with SonoVue contrast agent for the first 3 years. Results: From January 1st to December 2008 we executed 60 CEUS, identifying thirteen suspected liver lesions. 10/13 were confirmed metastases by CT, MRI or TC/PET. 2/13 resulted benign lesions. 1/13 resulted negative at the CT but positive with a MRI. Another additional case was missed by CEUS but detected by CT. CEUS improve specificity and sensitivity compared with baseline ultrasonography. We had an histological confirmation in all cases except one. The study is still recruiting patients. Conclusions: The clinical value of CEUS as a reliable alternative to CT or MRI in characterizing focal liver lesions has been expressed in various documents and guidelines. Our preliminary results confirm the similar diagnostic performance and confidence of CEUS compared to these imaging modalities in the follow up of CRC. Further clinical studies are still needed to strenghten the existing data. No significant financial relationships to disclose.
Can Kampo medicine prolong the life of metastatic colorectal cancer (MCRC) patients with chemotherapy?
Authors: Sasaki K. , Oono K. , Harada K. , Someya T. , Takada Y. , Furuhata T. , Hirata K. 
Published: August 2020

e15120 Background: Many in vivo and in vitro studies have shown that Kampo medicine has various biological and immunological activities, including anti-cancer effect. However, we have little data on efficacy of survival period on MCRC patients (pts) with chemotherapy and Kampo therapy. The aim of this study was to evaluate the survival benefit on MCRC pts treated with Kampo medicine and chemotherapy. Methods: From 2002 to 2007, we treated 66 patients with MCRC. These patients were treated with chemotherapy (CPT-11 + S-1) and/or Kampo medicine (Jyuzen-Taiho-To, TJ-48) on out-patient basis. TJ-48 was given orally at a dose of 7.5g, three times daily. We randomly divided the MCRC pts following two treatment groups; chemotherapy plus Kampo medicine (Group A, n=33) and chemotherapy only (Group B, n=33). Results: Pts and tumor characteristics were much the same between the two groups at baseline. Pts treated with Kampo medicine in combination with chemotherapy (Group A) had a median survival of 20.5 months compared with 15 months for Group B (p=0.12). One and 2 years survival rates were 72% and 13%. No toxic death was reported. The overall 1, 2 and 3 years survival rate were 69, 24 and 12% respectively in Group A, 57, 0 and 0% in Group B. Adverse events did not increase in Group A. TJ-48 is low cost medicine ($1.8 / day). All patients were treated on an out-patient clinic. Conclusions: These results confirmed that the Kampo medicine is helpful and capable of prolonging the survival periods in pts with MCRC. No significant financial relationships to disclose.
Feasibility of treatment of resectable rectal cancer with neoadjuvant treatment with pemetrexed
Authors: Carlsson G. , Bjökqvist H. , Kurlberg G. , Torbjörn S. , Casillas M. , Holmqvist M. , Stoffregen C. , Gustavsson B. 
Published: August 2020

e15121 Background: Multimodality strategies of chemo- and radiotherapy (RT) in the neoadjuvant setting of resectable rectal cancer are a challenge to optimize surgery outcome. Pemetrexed (P) has shown efficacy in colorectal cancer. This phase II trial evaluated its feasibility as neo-adjuvant monotherapy for patients (pts) with resectable rectal cancer. Methods: Between June’ 06 and January’ 08, 37 pts with a histologically proven diagnosis of operable rectal adenocarcinoma were enrolled. P was dosed at 500 mg/m2 every 3 weeks, during 3 cycles with standard co-medication (vitamin B12, folic acid, and dexamethasone) on an outpatient base. If RT was given, minimum interval between start of RT and last dose of P was 2 weeks, preferably 5 consecutive days of RT occurred from day 17 to day 21 in cycle 3 or after completion of cycle 3. The feasibility hypothesis was that at least 85% of pts would be able to receive the chemotherapy as planned. Secondary endpoints were evaluation of qualitative and quantitative toxicities including rate of postoperative complications, proportion of pts with sphincter saving surgery, proportion of pts with complete tumor resection rate and pathological response rate. Results: All patients were able to receive 3 cycles of chemotherapy. 33 patients (89.2%, CI: 74.6 to 97) completed their planned dosage in time. The reason for delay was inadequate vitamin supply for 1 pt and 3 pts due to other reasons. No dose reduction or study-drug related SAE was seen. The only grade 3 and 4 toxicities (neutropenia) occurred in 7 pts (18.9%). 28 pts received RT following chemotherapy. All pts underwent R0 resection. One pathological proven complete response was evaluated. 12 out of 13 planned pts had a rectum amputation. All others received sphincter saving surgery. Postoperative complications occurred in 54% of the pts. All events were considered related to study procedure (operation) and not to study drug. Conclusions: This explorative study suggests that the administration of 3 cycles of pemetrexed is feasible and well tolerated within a multimodality treatment strategy. [Table: see text]
Outcome of initially unresectable advanced and metastatic colorectal cancer patients treated with first-line mFOLFOX6 followed by surgical tumor removal of metastases: Preliminary results of a phase II trial
Authors: Hasegawa J. , Yoshida Y. , Mizushima T. , Fujii M. , Mizuno H. , Tamagawa K. , Nezu R. 
Published: August 2020

e15122 Objective: The aim of this study was to evaluate the efficacy and tolerability of treatment with mFOLFOX6 followed by surgical tumor removal in patients (pts) with initially unresectable liver metastases and/or extrahepatic disease from colorectal cancer (CRC). Methods: This study was a multicenter, open-label clinical trial. Eligibility criteria defined pts with advanced and metastatic CRC deemed not optimally resectable. mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, and fluorouracil [400 mg/m2 bolus followed by 2,400mg /m2 as a continuous 46-hour infusion]) was administered every 2 weeks for a maximum of 10 cycles. Resectability was the primary end point. Results: 26 pts (15M/11F; PS 0/1 19/7; median age: 60 years, rage 37–73) received 181cycles (median 7, range, 3–10) of mFOLFOX6. Main unresectable lesions were liver metastases in 10 pts and extrahepatic disease in 16 pts. Eleven pts (42%) had at least one grade 3 or greater adverse events. Sixteen pts (61%) achieved an objective response to mFOLFOX6 and 8 pts (31%) had a best overall response of stable disease. In 16 of these 24 pts who achieved the disease control, surgical tumor removal was performed (resectability 61%). The main reasons for initial unresectability in these 16 pts were the presence of liver metastases (6 pts), para-aortic lymph-node metastases (4 pts), carcinomatous peritonitis (4 pts), direct invasion to neighboring organ (2 pts). Four complications (25%) which were anastomotic leak, wound infection, chylous ascites, and cholangitis, were observed. At a median follow-up of 13 months (range 5 -21), 5 pts had relapsed after surgical tumor removal. The median time to progression (TTP) of the pts who underwent operation is not reached to date and those who did not undergo surgical removal is 8.6 months (log-rank p<0.05). Conclusions: Our data suggest that mFOLFOX6 has a significant antitumor activity in pts with not only liver metastases but also extrahepatic disease from CRC, allowing for successful resection of disease in a portion of pts initially not judged to be optimally resectable. No significant financial relationships to disclose.
Phase I trial of advanced generation anti-CEA designer T cells in gastrointestinal and breast cancers
Authors: Junghans R. P. , Abedi M. , Bais A. , Gomes E. , Ma Q. , Beaudoin E. , Davol P. 
Published: August 2020

e15123 Background: We created “designer T cells” by retroviral gene therapy to express chimeric immunoglobulin-T cell receptors (IgTCR) with specificity for carcinoembryonic antigen (CEA). Our previous Phase I trial with 1st generation (1st gen) designer T cells was well tolerated with proof-of-principle “biologic responses”, but of limited duration. Lab correlates showed modified T cells repeatedly kill tumor targets over 4–7 days but then undergo activation-induced cell death (AICD). We created 2nd gen designer T cells that incorporate CD28 co-stimulation into the IgTCR (IgCD28TCR), suppressing AICD and promoting T cell proliferation on tumor contact with superior tumor responses in vivo (Emtage et al. Clin Cancer Res 2008;14:8112). A Phase I clinical trial was approved under FDA BB-IND 10791. Methods: Patient T cells are modified ex vivo, expanded and then administered in a Phase Ia dose escalation, spanning doses of 10^9 to 10^11 cells. Patients are monitored for safety, pharmacokinetics and response. Results: To date, three subjects enrolled with doses prepared and two were treated. T cells were transduced with equal modification of CD4 helper and CD8 cytotoxic T cells and good ex vivo expansions of 30-fold or more. Cells were infused over 15–30 minutes. Blood clearance was rapid. Dosing was without toxicity but also without responses at this lowest T cell dose level. Results will be updated to include new patients at conference time. Conclusions: The safety of 2nd generation designer T cells is supported in two patients at the lowest T cell dose level. Higher planned doses are 10- to 100-fold more T cells, to be observed for toxicity and where responses may begin to be observed. Funding is from the Office of Orphan Products Development of the FDA. No significant financial relationships to disclose.
Functional profiling in stage IV colorectal cancer: A phase II trial of individualized therapy
Authors: Blitzer J. B. , Shbeeb I. , Neoman A. , Azaren K. , Paulsen M. , Evans S. , Nagourney R. 
Published: August 2020

e15124 Background: The introduction of new classes of agents has improved survival in colorectal cancer (CRC) yet the accurate selection of candidates for these often costly & toxic drugs remains a challenge. Genomic platforms have identified several prognostic & predictive factors e.g. ERCC1, TS, kRas mutations but the comparatively small number of known cellular analytes has limited their broad application. Methods: To address the complexity and redundancy of cell-death signaling pathways, we applied Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) (Nagourney, R. Curr Treat Options in Oncol. 2006) to select therapies for chemo-naïve pts with metastatic CRC. This functional platform uses morphologic and metabolic endpoints to gauge cellular response to drugs & signal transduction inhibitors in human tumor microspheroids isolated from surgical biopsies. Modified Z-scores & synergy analyses (median-effect) were used to identify the ex vivo best regimen (EVBR) for each pt. from FDA-approved CRC drugs. All pts signed informed consent. Results: 12/13 (92%) pts are evaluable. Of the 12 there was 1/12 (8%) CR; 7/12 (58%) PR; 3/12 (25%) SD & 1/12 (8%) PD for an ORR = 8/12 (66%) & CBR = 11/12 (92%). 1st line EVBR were FOLFOX 3/12 (25%); FOLFIRI 2/12 (16%); FOLFOX/Erbitux 2/12(16%); FOLFOX/Avastin 1/12 (8%); FOLFOX/Avastin/Erbitux 1/12(8%); Irinotecan/Avastin/Erbitux 2/12(16%); IROX/Avastin 1/12(8%). Three of 12 inoperable pts (25%) converted to surgical candidates. There was 1 treatment-related death. Accrual continues with current TTP ranges from 1.2–17.3 months and OS from 2.5 to 30 months. Conclusions: EVA/PCD ORR in Stage IV CRC of 66%, many durable, compares favorably with reports in this population. By examining drug-induced cell death events in native-state microspheroids, this platform has the unique capacity to capture stromal, vascular and inflammatory cell interactions with tumor cells, now known to be crucial for clinical response prediction. EVA/PCD analysis warrants further evaluation in CRC. Supported by the Memorial Medical Center Foundation of Long Beach. [Table: see text]