bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase IV study of first-line bevacizumab plus irinotecan and infusional 5-FU/LV in patients with metastatic colorectal cancer: AVIRI
Authors: Sobrero A. F. , Young S. , Balcewicz M. , Chiarra S. , Perez Carrion R. , Mainwaring P. , Gapski J. , Clarke S. , Langer B. , Ackland S. 
Published: March 2020

4068 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumour angiogenesis by targeting VEGF. In a phase III trial (AVF2107g), BEV significantly improved overall (OS) and progression-free survival (PFS) when combined with first-line irinotecan plus bolus 5-fluorouracil (5-FU)/leucovorin (LV) (IFL) in patients with metastatic colorectal cancer (mCRC). A multicentre, open-label trial is being conducted to evaluate the efficacy and safety of first-line BEV in combination with irinotecan and infusional 5-FU (FOLFIRI), a widely used first-line chemotherapy (CT) regimen. Methods: Patients had to have: mCRC; no surgery within 28 days; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. CT consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI regimen; variations like the simplified FOLFIRI and the weekly regimen were also allowed. BEV 5mg/kg was given on day 1 with CT and then every 2 weeks until disease progression. Tumour assessments were performed every 3 months during the first 12 months and every 4 months thereafter. Safety was assessed at the time of CT administration and every 4 weeks thereafter. The primary objective was PFS; secondary objectives included safety, overall response rate, time to response, duration of response and OS. Results: A total of 209 patients were enrolled at 31 centres worldwide, between April and November 2005. An interim analysis showed that the safety profile of BEV plus FOLFIRI appeared to be similar to that reported for Avastin plus IFL. The 44% overall response rate and 90% disease control rate are at least equivalent to that reported in comparable trials. Additionally, the 6 months PFS estimate of 82% was superior to that reported in AVF2107. Mature PFS data will be presented. Conclusions: AVIRI is the largest clinical trial, to date, to report data for BEV in combination with FOLFIRI in first-line patients with mCRC. The safety profile appears consistent with that observed in other BEV trials in mCRC, while the preliminary efficacy data suggest that this regimen is as active as the bolus regimen. No significant financial relationships to disclose.
Safety and efficacy of first-line irinotecan/fluoropymidine combinations in mCRC patients >65 years compared with those ≤65: The BICC-C study
Authors: Barrueco J. , Marshall J. , Mitchell E. , Wierzbicki R. , Ganju V. , Jeffery M. , Schultz J. , Richards D. , Soufi-Mahjoubi R. , Fuchs C. 
Published: March 2020

4076 Background: BICC-C was a multicenter, randomized study that assessed efficacy & safety of irinotecan/fluoropyrimidines combinations in previously untreated mCRC patients. This study showed that FOLFIRI or FOLFIRI+bev were superior to their comparators (Proc ASCO 2006). We conducted a secondary analysis of efficacy & safety among all patients >65 years compared with those =65. Methods: Pts were randomized to: infusional FOLFIRI, modified bolus IFL (mIFL), or CapeIri; and concurrent celecoxib or placebo in a double-blind fashion. The protocol was amended in April 2004 and bevacizumab (bev) was added to the FOLFIRI and mIFL arms whereas CapeIri was discontinued. Period 1 (P1) and Period 2 (P2) designate subjects enrolled before or after the amendment. Results: Of 430 pts enrolled in P1, 150 were age >65 (median 71; range, 66–87) and 280 were = 65 (median, 56; 20–65). Of 117 pts in P2, 75 were >65 (median, 73; 66–84) and 42 were = 65 (median, 54; 32–65). No significant differences in efficacy or safety were observed between the two age groups. Results for P1: median progression free survival (PFS) was 6.5 and 6.7 mos; and median overall survival (OS) was 18.8 and 19.2 for >65 and =65, respectively. For the FOLFIRI regimen specifically median PFS was 7.5 and 7.6 mos, and median OS was 20.1 and 24.3 mos for >65 and =65, respectively. Results for P2: median PFS was 10.3 and 10.6 mos; and median OS was 19.8 and 23 mos for >65 and =65, respectively. For the FOLFIRI+bev regimen specifically median PFS was 11.1 and 11.2 mos for >65 and =65 respectively, and median OS has not yet been reached for either subgroup at time of analysis. Common grade = 3 AEs are listed below. Conclusions: Efficacy and safety for first line irinotecan/fluoropyrimidine regimens and for FOLFIRI & FOLFIRI+bev, specifically, did not differ for older and younger mCRC patients. [Table: see text] [Table: see text]
Impact of irinotecan and oxaliplatin on overall survival in patients with metastatic colorectal cancer (MCRC): A population- based study
Authors: Lim H. J. , Fitzgerald C. , Gill S. , Melosky B. , Speers C. , Barnett J. , Kennecke H. 
Published: March 2020

4077 Background: Over the past 10 years, chemotherapeutic options for MCRC has significantly expanded from 5-FU based therapy, to include irinotecan and oxaliplatin. The effect of the availability of these treatments on overall survival is evaluated among patients in 3 time cohorts referred to the British Columbia Cancer Agency (BCCA). Methods: Patients with newly diagnosed or relapsed metastatic colorectal cancer referred to the BCCA in 1995/96, 2000 and 2003/04 were included. In 1995/96, 5-FU was the only palliative chemotherapy agent available at BCCA and irinotecan and oxaliplatin were available in 2000 and 2003, respectively. A one year period was used for the irinotecan cohort to minimize overlap between groups. Overall survival estimates were generated using the Kaplan Meier method. Survival was calculated from time of diagnosis of distant metastatic disease to either death or last contact date. Results: Cohorts were generally similar, however, a significantly higher proportion of patients received chemotherapy in more recent eras ( Table 1 ). Only 25% of patients received both irinotecan and oxaliplatin in 2003/4 and only 10 % received biologic therapies. An improvement in median survival of 3.6 months was observed. The improvement in the treated subgroup was 4.2 months. Outcomes of patients untreated with chemotherapy were unchanged between cohorts. Conclusions: In this population based study, the proportion of patients with MCRC treated with chemotherapy significantly increased between 1995/6 and 2000/2003/4. Patients treated with chemotherapy experienced a 4.2 month increase in median survival in 2003/4 compared to 1995/6. Survival improvements were only significant in the time period when all three effective chemotherapies (5FU, irinotecan and oxaliplatin) were available. As bevacizumab was not available until 2006, its survival impact in this population is not yet known. [Table: see text] No significant financial relationships to disclose.
Targeted chemoradiation for metastatic colorectal cancer: A phase I trial of oral capecitabine combined with 131I- huA33
Authors: Herbertson R. A. , Tebbutt N. , Gill S. , Lee F. T. , Chappell B. , Cavicchiolo T. , Skrinos E. , Poon A. , Saunder T. , Scott A. M. 
Published: March 2020

4078 Background: HuA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and >95% of human colon cancers, but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 weeks, but eliminated from normal colonocytes within days. This phase 1 study used radio-labeled huA33 in combination with capecitabine chemotherapy to target chemoradiation to metastatic colorectal cancer. Methods: The primary objective was safety and tolerability of the combination of capecitabine and 131I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Eligibility included measurable metastatic colorectal cancer, adequate hematological and biochemical function, and informed consent. An outpatient scout 131I-huA33 dose was followed by a single therapy infusion one week later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the12 week trial. Tumor targeting was assessed using gamma camera and single photon emission computerized tomography (SPECT) imaging. Results: 16 patients have enrolled with 2 currently on treatment, including one in the final dose cohort. Accrual will be completed by March 2007. The dose escalation protocol was amended following 2 dose limiting toxicities in the second cohort, but subsequent cohorts demonstrated good tolerability. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. Maximal duration of stable disease is currently 3 years. Conclusions: 131I-huA33 achieves specific targeting of radiotherapy to sites of metastasis and can be safely combined with chemotherapy. This provides an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients. [Table: see text] No significant financial relationships to disclose.
Cost-minimization analysis of a phase III study of capecitabine + oxaliplatin (XELOX) vs. infusional 5-FU/LV + oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer (MCRC) in the French setting
Authors: Perrocheau G. , Bennouna J. , Ducreux M. , Hebbar M. , Ychou M. , Lledo G. , Conroy T. , Adenis A. , Faroux R. , Douillard J. 
Published: March 2020

4083 Background: A recent phase III trial in first-line MCRC showed that XELOX is well tolerated and non inferior to FOLFOX-4 in terms of progression-free survival (PFS) [Cassidy ESMO 2006]. We conducted a phase III trial of XELOX vs. FOLFOX-6 as first-line treatment for MCRC. Methods: 306 patients were randomized to receive either XELOX (n=156: capecitabine 1,000mg/m2 bid d1–14, oxaliplatin 130mg/m2 d1, q3w) or FOLFOX-6 (n=150: oxaliplatin 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400- 3,000mg/m2 46h infusion, q2w) for 6 months. Primary objective: demonstrate non-inferiority of XELOX (best response rate, RECIST). A cost minimization has been conducted from the French hospital perspective. The hospitalizations for chemotherapy (drug administration) were compiled and the direct hospital costs estimated using official tariffs of the national ‘PMSI’ database, directly derived from the Diagnosis Related Group (DRG). Results: The ITT population comprises 306 patients (156 on XELOX, 150 on FOLFOX-6). Baseline characteristics were well balanced. Patients received an average of 6.1±2.4 and 9.2±3.2 cycles of XELOX and FOLFOX-6, respectively. The number of hospitalizations was 6.5±2.6 and 9.5±4.1 for XELOX and FOLFOX-6, respectively. The costs of hospitalization for chemotherapy are available for 282 patients (142 in the XELOX arm and 140 in the FOLFOX-6 arm). The average cost of chemotherapy per cycle per patient was 608±446€ in the XELOX arm and 1,043±787€ in the FOLFOX-6 arm (p<0.001). Conclusions: As we have shown in the efficacy and safety abstracts also presented at this meeting, XELOX is non inferior to FOLFOX-6 in terms of best response rate with a comparable safety profile. In addition, XELOX appears to decrease hospital resource consumption compared with FOLFOX-6. No significant financial relationships to disclose.
Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (LV) (SCOUT) in patients with advanced colorectal cancer (ACRC): A phase I/II study
Authors: Sheikh H. , Valle J. W. , Palmer K. , Wilson G. , Sjursen A. , Craven O. , Swindell R. , Saunders M. P. 
Published: March 2020

4084 Background: The feasibility of UFT (tegafur-uracil) plus LV with alternating irinotecan and oxaliplatin was investigated in a two-stage, phase I/II, open-label, dose-finding trial in patients with ACRC. The study is now closed. Here we present results from the phase II cohort and overall results from the phase I/II study. Methods: Eligible patients aged =18 years had histologically confirmed, advanced, inoperable, measurable metastatic disease, no prior chemotherapy other than adjuvant bolus 5-FU administered =6 months previously, and adequate hematologic, hepatobiliary, and renal function. Patients in the phase I study received irinotecan 180 mg/m2 on d1, oxaliplatin 85–100 mg/m2 on d15 plus UFT 200–300 mg/m2/d with LV 90 mg/d on d1–21 of a 28-d cycle. Diarrhea, lethargy, and vomiting were dose limiting. The maximum tolerated dose (MTD) established was irinotecan 180 mg/m2, oxaliplatin 100 mg/m2, UFT 250 mg/m2/d, and LV 90 mg/day. Patients were treated at the MTD in the phase II study. Primary endpoints in the phase II study were objective response rate (ORR) and time to progression (TTP). Results: Forty-five patients (median age 62 [range 24–79] years, median 4 marker lesions) were entered, 16 and 29 patients in the phase I and II studies, respectively. The ORR in all 38 evaluable patients was 66% (95% CI 49–80%), with clinical benefit (CB) in 89% (95% CI 75–97%). At a median follow-up of 10.3 months, median TTP was 8.5 months (95% CI -7.6 to 10.4 months) in 40 evaluable patients and median OS (ITT population; n=45) was 16.8 months (95% CI -11.3 to 28.3 months). In the phase II study (n=29) median TTP was 8.1 months (95% CI -6.7 to 11.3 months) and median OS was 19.6 months (95% CI -7.7 to >25.6 months); ORR in 25 evaluable patients was 68% (95% CI -46.5 to 85.1%) with CB in 100% (95% CI -86.3 to 100%). Of 30 patients with confirmed radiologic progression, 21 (70%) had second-line therapy. At the MTD, 3 patients (10%) had grade 3 diarrhea, 1 patient (3%) had grade 3 neurotoxicity, and 2 patients (7%) had grade 2 alopecia. No hand-foot syndrome (HFS) was seen. Conclusions: UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for patients with ACRC, with minimal alopecia and neurotoxicity and no HFS. No significant financial relationships to disclose.
Phase I study of oral S-1 in combination with oxaliplatin (oxali) and bevacizumab (bev) in patients with advanced solid tumors
Authors: Zhang J. , Chung K. , Zergebel C. , Urrea P. , Quinones M. , Saltz L. 
Published: March 2020

4091 Background: S-1 is a novel oral fluoropyrimidine (tegafur, CDHP and potassium oxonate) designed for enhanced DPD inhibition and reduced GI toxicity. Bev and oxali have demonstrated safety and synergistic anti-tumor activity with oral and IV fluoropyrimidines. The primary objective is to investigate the safety and maximum tolerated dose (MTD) of S-1 combined with bevacizumab and oxaliplatin in patients with advanced solid tumors. Secondary objective is to investigate the clinical pharmacokinetics (PK) of the components of S-1 (FT, CDHP, Oxo), 5-FU, a-fluoro-β-alanine, cyanuric acid, uracil, and oxali and to document any antitumor activity. Methods: ECOG 0/1 patients with advanced or metastatic solid tumors received oral S-1 starting at 20 mg/m2/dose BID x 14 days (classic 3+3 cohort dose escalation by 5mg/m2/dose until MTD), plus fixed doses of bev 7.5 mg/kg IV day 1, and Oxali 130 mg/m2 IV day 1 of every 3 week cycle, with discontinuation of oxali after 4 cycles. Reintroduction of oxali was allowed upon progression of disease. Toxicity, antitumor activity and PKs were assessed. The MTD was defined as the highest dose level at which < 33% of the patients experience a dose- limiting toxicity (DLT) during the first 2 cycles. Results: Of 22 evaluable patients, 3 patients were treated at 20mg/m2 S1 and 13 patients were treated at 25mg/m2 S1 without a DLT. At 30mg/m2, two patients experienced a DLT(Grade 3 diarrhea, Grade 4 mucositis). The MTD and recommended phase II dose of S-1 is 25mg/m2 in combination with oxali and bev. A median of 8 cycles of S-1 were initiated at the 25 mg/m2 dose level. Common MTD level toxicities included fatigue (62%), nausea (62%) and diarrhea (46%), with no grade 4 toxicities observed. Best responses (RECIST): stable disease(16 patients), partial response (2 patients), non-measurable disease (3 patients). The Day 8 AUC(0–8) of 5-FU at 20/25/30 mg/m2 dose level were 230±115 hr*ng/ml, 470±172 hr*ng/ml and 502±169 hr*ng/ml, respectively. Conclusions: The MTD combination of 25mg/m2 S-1, oxali and bev can be given safely. The study will be expanded to test S-1 one week on, one week off schedule in combination with oxali/bev every two weeks. No significant financial relationships to disclose.
Phase II study of the A-ICOX regimen [bevacizumab (Bev), weekly intermittent capecitabine (Cap) and oxaliplatin (Ox)] for untreated advanced colorectal cancer (CRC)
Authors: Ramanathan R. K. , Rajasenan K. , Crandall T. , Balaban E. P. , Pinkerton R. A. , Kane P. , Potter D. M. , Dranko S. , Schmotzer A. , Lembersky B. C. 
Published: March 2020

4092 Background: FOLFOX in combination with Bev is a standard regimen for treating advanced CRC. Cap on a d 1–14 schedule every 3 weeks is now being substituted for 5-flurouracil (CapOx); however optimal doses and schedules of Cap in combination with Ox and Bev needs continued evaluation. Intermittent weekly Cap (3,500 mg/m2, d 1–7) with Ox (85 mg/m2) every 2 weeks compared to the standard CapOx regimen in untreated advanced CRC has shown superior response and time-to-progression in Europe (Scheithauer W et al. J Clin Oncol. 21,1307; 2003). Methods: This phase II trial is designed to evaluate the A-ICOX regimen in US patients with CRC. The primary endpoint is to detect a 50% improvement in median progression free survival (PFS) from 8 to 12 months. With a sample of 40 patients, a 1-sided level 0.1 log-rank test has 81% power to detect this difference. Patients with advanced untreated CRC are eligible for study. Cap is administered at the dose of 2,500 mg/m2 in two divided doses on d 1–7 (n=11) and has been increased to 3000 mg/m2 dose (n=26), based on tolerability of the lower dose. The dose of Ox is 85 mg/m2 and Bev is 5 mg/kg. Cycles are repeated every 2 weeks. Results: Thirty-seven of 40 pts have been enrolled, with 30 evaluable for toxicity and response. Patient characteristics: Male (n=19); ECOG performance status 0 (n=18), 1 (n=12); median age 63 (range 38–80 years). Median cycles administered 4 (range 1–17). Partial responses were seen in 10 pts (33%), and metastasectomy was performed in 8 pts (27%). The PFS analysis is premature at this point. Gr 3/4 hematological toxicity occurred in only 2 pts (7 %). Other gr 3/4 adverse events have included: diarrhea (10 %), hand-foot syndrome (7 %), peripheral neuropathy (7%), nausea (7%) and vomiting (7 %). Conclusions: The first US experience of the A-ICOX regimen shows it to be very well tolerated, and Cap (3,000 mg/m2, d 1–7) in combination with Ox and Bev therapy can be safely administered. The incidence of subsequent metastasectomy, a marker of activity, is encouraging. A phase III trial of the A-ICOX regimen is now being conducted against standard Q-3 weekly CapOx/Bev. (Study supported by Genentech and Roche Pharmaceuticals) [Table: see text]
The combination of capecitabine (C), irinotecan (I) and oxaliplatin (O) (XELOXIRI) as first line treatment of metastatic colorectal cancer (MCRC): Preliminary results of a pilot study by the Gruppo Oncologico Nord-Ovest (G.O.N.O.)
Authors: Masi G. , Bursi S. , Loupakis F. , Barletta M. , Baldi G. , Antonuzzo A. , Sonaglio C. , Pfanner E. , Petrini I. , Falcone A. 
Published: March 2020

4096 Background: FOLFOXIRI demonstrated manageable toxicities and improved activity and efficacy compared to FOLFIRI in MCRC in a phase III trial by the G.O.N.O. group. Oral C has demonstrated similar efficacy to 5-FU and might substitute 5-FU in the FOLFOXIRI regimen. Methods: The G.O.N.O. started a pilot study to evaluate the combination of escalating doses of C with fixed doses of I, O (XELOXIRI) in metastatic and not resectable CRC patients (pts). The objectives of the study are the definition of the recommended dose (RD) of C in combination with I and O, safety and activity of the combination and analysis of plasma pharmacokinetics. The planned treatment in the first 3 patients was: I 165 mg/sqm over 1-h on day 1, O 85 mg/sqm over 2-h on day 1 and C 2,500 mg/sqm/die from day 1 to 7, repeated every 2 weeks. C dose was increased to 3,000 mg/sqm/die or decreased to 2,000 mg/sqm/die in subsequent groups of 3 to 6 pts on the basis of the observed dose limiting toxicities (DLT). Results: Up today 33 patients have been enrolled. Main patients characteristic are: sex (M/F) = 22/11, PS (0/1/2) = 28/4/1, age (median/range) = 65/42–76, sites of disease (single/multiple) = 18/15. The DLT was G3–4 diarrhea that was observed in 2 out 6 patients receiving C at 2500 mg/sqm, in 2 out 3 patients receiving C at 3,000 mg/sqm and in 1 out 6 patients receiving C at 2,000 mg/sqm. This last dose was defined the RD. Among the 23 patients treated at the RD main G3–4 toxicities were: diarrhea 17%, neutropenia 26%, thrombocytopenia 9%, neurotoxicity 4%. One toxic death for diarrhea and sepsis occurred. Up today 21 out of the 23 patients (2 patients too early) treated at the RD are assessable for response (ITT analysis) and 15 RP, 3 SD and 3 treatment failures have been observed with a response rate of 71% (95% CI: 48–89%). At a median follow-up of 10.3 months median PFS is 9.0+ months and median OS isn’t yet reached. Conclusions: XELOXIRI is a feasible regimen with diarrhea being the DLT. The recommended dose of C is 2,000 mg/sqm. At the RD toxicity is manageable and preliminary results in terms of activity are promising. Partially supported by Fondazione ARCO. No significant financial relationships to disclose.
Antitumour activity of pemetrexed (Pem) and irinotecan (Iri) in second-line metastatic colorectal cancer (MCRC) patients: A multicenter phase II study
Authors: Louvet C. , Andre T. , Gamelin E. , Hebbar M. , Mabro M. , Bennamoun M. , De Gramont A. 
Published: March 2020

4103 Introduction: 5FU + Iri (i.e. FOLFIRI) is a validated second line treatment after 5FU + Oxaliplatin (i.e. FOLFOX) induction in MCRC, with a response rate ranged from 10 to 15%. Pem is a multi-antifolate with wide range of target inhibition as compared to 5FU suggesting that Pem + Iri could have a better efficacy as compared to FOLFIRI. We then studied the antitumour activity and the safety of Pem + Iri combination in patients treated with FOLFOX for MCRC. Methods: Forty-six patients with measurable second line MCRC and no brain metastases were included in this trial. Pem 400 mg/m2 over 10min on d1 with folic acid and vitamin B12 supplementation followed by Iri 180 mg/m2 (90min) on the same day were given q2w for 12 cycles. Results: 44/46 patients (95%) received at least one cycle of the combination with median age: 63 yrs, baseline ECOG performance status = 2: 100%. Metastatic sites were: liver: 70%, lung: 41%, lymph node: 7% and peritoneum: 5%. The median number of administered cycles was 4.5. Seven out of 44 patients (16%) received at least 12 cycles of study therapy. The objective response rate (intent-to-treat, RECIST criteria, assessed by investigators) was 14% (95% CI [5.2; 27.4]), 41% had stable disease. Grade 3/4 toxicities were: neutropenia: 19%, anemia: 9%, elevated AST/ALT 10%, diarrhea: 16%, vomiting: 7%, nausea: 5% and fatigue: 20% which was the most limiting toxicity for this combination. Conclusion: The combination of Pem + Iri is active in second line MCRC. However, response rate seems to be in the same range as compared to historical data for FOLFIRI. Patients are still in the follow-up period. Data of PFS and OS will be presented at the meeting. No significant financial relationships to disclose.