bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of the anti-IGFR antibody MK-0646 in combination with cetuximab and irinotecan in the treatment of chemorefractory metastatic colorectal cancer
Authors: Watkins D. J. , Tabernero J. , Schmoll H. J. , Trarbach T. , Ramos F. J. , Hsu K. , Gates M. , Clark J. , LeVan P. , Cunningham D. 
Published: August 2020

4127 Background: Evidence of cross-talk between EGFR and IGFR signaling pathways provide a logical rationale for combining anti-EGFR and anti-IGFR strategies in the treatment of cancer. Prior to commencing a blinded randomised phase II study, an opened-labelled safety run-in was undertaken to assess the tolerability of a three-drug combination utilizing irinotecan (Ir), cetuximab (Cx) and two schedules of MK-0646 (Mk). Methods: Eligible patients (pts) had previously failed both Ir and oxaliplatin and had progressed on or within 3 months of their last therapy. Pts were required to have measurable disease and tissue samples available for tumour KRAS testing. Pts were randomised to receive either Mk 10mg/kg weekly (Arm A) or Mk 15mg/kg loading followed by 7.5mg/kg every alternate week (Arm B). All randomised pts also received Cx 400mg/m2 loading followed by 250mg/m2 weekly and Ir according to the same dose and schedule as they had previously received. Patients continued on treatment until disease progression with radiological response assessments undertaken every 6 weeks. Results: 10 pts were recruited to Arm A and 8 to Arm B. Pt characteristics: median age 60.5 years, male 67%, PS 0/1 33%/67%. Median number of prior chemotherapy regimens 3. The median number of cycles of Mk received in Arm A and B is 25 and 8 respectively. Reported grade III/IV toxicities in Arm A and Arm B were: neutropenia 30% and 0%, diarrhoea 30% and 25%, hypomagnesemia 0% and 25%. Hyperglycemia (≥ grade 2) was seen in 10% of Arm A and 25% in Arm B. Acneiform skin toxicity (≥ grade 2) was seen in 30% of Arm A and 62% of Arm B. The radiological response rate was 33% in Arm A and 14% in Arm B. The median time on study drug is 5.8 months in Arm A and 3.9 months in Arm B. 2 pts on Arm A and 1 in Arm B remain on study therapy. Tumour KRAS testing is in progress. Conclusions: The combination of MK-0646, cetuximab and irinotecan is tolerable with no concerning overlapping toxicities highlighted. PFS and KRAS data will be available for presentation. The efficacy of this three drug combination is under evaluation in an ongoing randomised phase II/III study. [Table: see text]
Analysis of survival with modified docetaxel, cisplatin, fluorouracil (mDCF), and bevacizumab (BEV) in patients with metastatic gastroesophageal (GE) adenocarcinoma: Results of a phase II clinical trial
Authors: Kelsen D. , Jhawer M. , Ilson D. , Tse A. , Randazzo J. , Robinson E. , Capanu M. , Shah M. A. 
Published: August 2020

4512 Background: Metastatic GE cancer is an aggressive disease with poor patient (pt) outcomes. Despite response rates of 30–60% to combination chemotherapy, response duration is usually 4–6 mo and 24-mo survival is 5–10%. The addition of BEV to chemotherapy has improved survival in several solid tumors, and has demonstrated encouraging activity in GE cancer (Shah et al, JCO 2006). We report mature tolerability and efficacy results of mDCF+BEV in GE cancer, with an emphasis on prolonged pt survival. Methods: Previously untreated metastatic GE pts with adequate end organ function received BEV 10mg/kg, Docetaxel 40mg/m2, FU 400mg/m2, Leucovorin 400mg/m2 on day 1, FU 1000 mg/m2/day x 2 days IVCI, and Cisplatin 40mg/m2 on day 3. Treatment is repeated every 14 days without prophylactic growth factor support. The primary objective is to improve 6-month progression free survival (PFS) from 43% (historical DCF control) to 63% with the addition of BEV. Target accrual is 44 evaluable pts, with 10% type I & II error. Secondary objectives include tolerability, response rates (RECIST), median PFS, 12-mo survival, and overall survival (OS). Results: Pt enrollment has completed: median age 57(range 29–74), median KPS 80% (70–100), M:F 32:12, gastric/GEJ/esophagus 22:17:5. In 39 patients with measurable disease we observed 26 confirmed partial responses (67%, 95% CI 50%- 81%), and 12 (31%) stable disease. Six-month PFS is 79% (95% CI 68%-93%), the median PFS is 12 mo (95% CI: 8.8–16). At median follow up of 12.3 mo, median OS is 16.2 mo (95%CI 11.4-infinitiy). 12- and 18-mo OS is 63% (95%CI 44–77%) and 46% (95%CI 27–63%), respectively. Minimal chemotherapy related grade 3–4 adverse events were observed: fatigue (20%), dehydration (13%), mucositis (9%), nausea/vomiting (7%), febrile neutropenia (4%). BEV related adverse event was perforation (n=1) and bleeding (n=1). 31% developed grade 3–4 venous thromboembolism, of which 93% were asymptomatic. No grade 3–4 hypertension, proteinuria or arterial thrombosis was observed. Conclusions: mDCF+BEV appears tolerable and has notable long term pt outcomes: 6-mo PFS is 79% (surpassing our efficacy endpoint), median OS 16.2 mo, and 18-mo OS 46%. No significant financial relationships to disclose.
A randomized controlled trial (RCT) comparing best supportive care (BSC), 5-FU plus folinic acid (FUFA) and, gemcitabine plus oxaliplatin (Gem-Ox) in management of unresectable gallbladder cancer (GBC)
Authors: Dwary A. D. , Sharma A. , Mohanti B. K. , Pal S. , Garg P. , Raina V. , Shukla N. K. , Deo S. V. , Thulkar S. , Sreenivas V. 
Published: August 2020

4521 Background: GBC is common in females residing in the northern part of India. Surgery is the only curative treatment. Unfortunately most patients present in advance and unresectable stage (median survival 3–4 months). Chemotherapy regimens for GBC are not yet standardized. Studies are few and mostly retrospective with small sample size and usually combine heterogeneous malignancies. Adequately powered RCT are not available. This was rationale to undertake study. Methods: It was single center, open label, three armed RCT. Ethical clearance was taken. Planned sample size was 81 to have type I & type II error probabilities of 0.05 & 0.2 respectively. Primary end point was to compare OS in unresectable GBC between BSC vs. FUFA vs. Gem-Ox arms. Secondary end points were to compare PFS in three arms and toxicity analysis of chemotherapy arms. Inclusion criteria were: proven unresectable GBC, performance state ≤2, adequate bone marrow reserve and normal biochemical profile (bilirubin≤3 mg % & liver enzymes within 5 times of upper limit). Patients in BSC group received symptomatic treatment without anticancer therapy. In FUFA group, weekly bolus doses of 5-FU (425mg/m2) plus Folinic acid (20 mg/m2) were given for a maximum of 30 weeks. In Gem-Ox group patients received gemcitabine (900 mg/m2) plus oxaliplatin (80 mg/m2) days 1 and 8 q3 weekly till maximum of 6 cycles. Results: Eighty one patients were randomized (BSC=27, FUFA=28, Gem-Ox=26). Median OS in BSC, FUFA and gem- Ox arms was 4.5 (CI 0.2–8.8), 5.3 (CI 3–6.2) and 9.3 (CI 5–14) months respectively (p= 0.039)). Median PFS was 2.8 (CI 1.8–3.8), 3.5 (CI 3.2–3.8) and 8.5 (CI 5.7–11.3) months in BSC, FUFA and Gem-Ox arm respectively (p= 0.0001). Chemotherapy arms were generally well tolerated. There was no difference in grade 3/4 toxicities in FUFA and Gem-Ox arm except for deranged liver function test, which was more in Gem-Ox arm (p=0.04). There was no toxic death. Conclusions: Probably this is the first RCT confirming efficacy of chemotherapy (Gem-Ox) compared to BSC in improving OS and PFS in unresectable GBC. Both chemotherapy arms were well tolerated. No significant financial relationships to disclose.
A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization
Authors: Lencioni R. , Malagari K. , Vogl T. , Pilleul F. , Denys A. , Watkinson A. , Lammer J. 
Published: August 2020

4523 Background: Transcatheter arterial chemoembolization (TACE) has been shown to offer a survival benefit for patients with intermediate-stage hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes the administration of a doxorubicin-in-oil emulsion followed by gelatine sponge particles. Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. Purpose of this randomized trial was to compare conventional TACE with DEB-TACE for the treatment of intermediate-stage HCC in patients with cirrhosis. Methods: Two hundred and twelve patients (185 males and 27 females; mean age, 67 years) with Child-Pugh A or B liver cirrhosis and large and/or multinodular, unresectable HCC were randomized to receive DEB-TACE (DC Bead; Biocompatibles, UK) uploaded with doxorubicin or conventional TACE with doxorubicin, lipiodol, and gelatin sponge particles. Randomization was stratified according to Child Pugh status (A or B), performance status (ECOG 0 or 1), bilobar disease (yes or no) and prior curative treatment (yes or no). Tumor response at 6 months was the primary study endpoint. An independent, blinded review of magnetic resonance imaging studies was conducted to assess tumor response according to amended RECIST criteria. Results: DEB-TACE with doxorubicin showed a higher rate of complete response, objective response and disease control compared with conventional TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%, respectively; p>0.05). Patients with Child Pugh B, ECOG 1, bilobar disease and recurrence following curative treatment showed a significant increase in objective response (p=0.038) compared to the control. There was a marked reduction in serious liver toxicity in patients treated with DEB-TACE. The rate of doxorubicin related side effects was significantly lower (p=0.0001) in the DEB-TACE group compared with the conventional TACE group. Conclusions: DEB-TACE with doxorubicin is safe and effective in the treatment of intermediate-stage HCC and may offer benefit to patients with more advanced disease. No significant financial relationships to disclose.
Drug eluting beads versus conventional TACE for unresectable hepatocellular carcinoma: Survival benefits and safety
Authors: Dhanasekaran R. , Kooby D. A. , Staley C. A. , Kauh J. S. , Kim H. S. 
Published: August 2020

4524 Background: Conventional transarterial chemoembolization (TACE) has long been used as palliative transcatheter therapy for patients with unresectable hepatocellular carcinoma (HCC). Drug eluting beads (DEB) are a newer drug delivery system that can be loaded with doxorubicin. Though therapy with DEB is feasible, the survival advantage of this therapy over conventional TACE has not been established. Methods: Consecutive patients who received transcatheter therapy with Doxorubicin DEB or conventional TACE as sole therapy over a period of 1998 to 2008 were studied. Patients who underwent resection, transplantation, radioembolization or combination therapies have been excluded from the study. Statistical analysis was performed using Kaplan Meier Estimator with a log rank test, Chi-square and independent T-tests. Results: A total of 73 patients were included in the study, 47(64.4%) received therapy with DEB (group A) and 26(35.6%) underwent conventional TACE (group B). The demographic, tumor burden and liver reserve characteristics of patients in the two groups were statistically similar. Median survival from diagnosis of HCC in group A and B were 610 days(352–866) and 284 days(4–563) (p=0.03). Median survivals from the time of first transcatheter therapy in group A and B were 403 days(373–679) and 114 days (183–460)(p=0.01). The survival rates in group A and B at 6 months, 1yr and 2 yrs were 71%, 66%, 40% and 58%, 46%, 19%. On analysis of patients in Child Pugh class A and B, median survivals in group A and B were 390 days(298–491) and 114 days(41–187)(p=0.004). No difference in survival was found in Child Pugh class C. 6.4%(3/47) of patients treated with DEB and 7.7%(2/26) of patients treated with conventional TACE developed liver failure in the post procedure period. All patients who developed liver failure belonged to Child Pugh class C. No other major complications were reported in either group. Conclusions: In patients with unresectable HCC, transcatheter therapy with Doxorubicin eluting beads offers a survival advantage over conventional TACE. The safety profile of the two treatment modalities appears similar. No significant financial relationships to disclose.
SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study
Authors: Von Hoff D. D. , Ramanathan R. , Borad M. , Laheru D. , Smith L. , Wood T. , Korn R. , Desai N. , Iglesias J. , Hidalgo M. 
Published: August 2020

4525 Background: Pancreatic cancer cells and surrounding stroma are known to overexpress SPARC (secreted protein acid rich in cysteine), which is associated with poor clinical outcomes. nab-P, an albumin-bound nanoparticle form of paclitaxel increased tumor accumulation of paclitaxel through binding of albumin to SPARC. This disease specific phase 1 study was designed to evaluate the safety and efficacy of G + nab-P and the correlation of response with tumor SPARC and serum CA19–9 levels. Methods: nab-P doses (100–150 mg/m2) + (G) (1000 mg/m2) were given on days 1, 8, and 15 of a 28-day cycle to pts with metastatic pancreatic adenocarcinoma and with no prior chemotherapy for their metastatic disease. Level 3 SPARC staining by immunohistochemistry was considered positive. Results: 63 pts received treatment. The most common grade 3 and 4 adverse event that occurred in >20% of pts was neutropenia. Nine (18%) pts and 4 (8%) pts had a grade 3/4 event, respectively. Neuropathy was also observed. One combination-associated death due to sepsis occurred at the 150 mg/m2 nab-P level. Serial PET scans of 53 pts with outside adjudication to date showed 12 (23%) complete responses, 29 (55%) partial responses (PRs) and 4 (8%) stable disease (SD). By RECIST criteria, of the 49 pts evaluable to date, 1(2%) had CR, 12 (24%) had PR, and 20 (41%) had SD. The median survival was 9 months to date. SPARC data were available for 35 pts, of which 10 (29%) were SPARC+ and 25 (71%) were SPARC-. Of these, 27 pts had evaluable response data. Pts that were SPARC+ (8/27) were more likely to be responders (6/8, 75%) than pts who were SPARC- (5/19, 26%), P = 0.03, Fisher's exact test. Median progression-free survival (PFS) increased from 4.8 months for SPARC- pts (22 pts) to 6.2 months for SPARC+ pts (9 pts); however, these data are still immature. Of 45 pts with elevated CA19–9 at baseline, 42 (93%) had maximum decrease of >40% with a median maximum decrease of 92%. Conclusions: The combination of nab-P and G was generally well tolerated and had substantial enough antitumor activity in patients with pancreatic cancer to warrant a phase III clinical trial. SPARC+ status in these patients was associated with higher response rate and longer PFS. [Table: see text]
Adjuvant gemcitabine alone versus gemcitabine-based chemoradiation after curative resection for pancreatic cancer: Updated results of a randomized EORTC/FFCD/GERCOR phase II study (40013–22012/9203)
Authors: Van Laethem J. L. , Mornex F. , Azria D. , van Tienhoven G. , Mauer M. , Praet M. , Budach V. , Hammel P. , Van Cutsem E. , Haustermans K. 
Published: August 2020

4527 Background: The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is debated. This randomized phase II intergroup study demonstrated the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer (Proc ASCO 2008, 4514). Long term and survival data are now reported. Methods: Patients were randomized within 8 weeks after surgery to receive either 4 cycles of gemcitabine 1000 mg/m2 given over 30 minutes every 3 weeks (control arm) or gemcitabine 1000 mg/m2 for 2 cycles followed by weekly gemcitabine 300 mg/m2 with concurrent radiation of 50.4 Gy given in 28 fractions of 1.8 Gy (experimental arm). The co-primary endpoints were completion of treatment and tolerability. Secondary endpoints were late toxicity, DFS and OS. Results: Between 9/04 and 1/07, 90 patients were randomized by 29 centers (45:45). Treatment arms were balanced in terms of patient/tumour characteristics. Follow-up was equal for both arms with an overall median follow-up of 27.1 months. In the control arm, 5 patients were ineligible, including 2 not treated. In the experimental arm, CRT was delivered to 36 of 45 patients (80%). Treatment was completed per protocol by 86.7% and 73.3% (80% CI 63.1–81.9%) of randomized patients in the control and experimental arms, respectively. Grade 4 toxicity was 0% and 4.4%, respectively. In the CRT arm, 2 patients experienced grade 3 late toxicity (anorexia 1 and epigastric pain 1). In the CRT experimental arm, 33 DFS events were noted and 23 deaths versus 34 and 24, respectively, in the control arm. Median DFS was 12 months in the experimental arm vs. 11 months in the control arm (p=0.6). Median overall survival was 24 months both in the experimental arm and the control arm. Distant progression was similar in both arms while the rate of first local recurrence was lower in the chemoradiation arm (11 vs 24 %, p=0.16). Conclusions: Post-op modern gemcitabine-based CRT is feasible and well- tolerated after long-term follow-up, and a larger trial should assess its true benefit to that of standard gemcitabine alone. [Table: see text]
Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer: Results from the AViTA Study
Authors: Verslype C. , Vervenne W. , Bennouna J. , Humblet Y. , Cosaert J. , Van Cutsem E. 
Published: August 2020

4532 Background: The EGFR inhibitor, erlotinib (E), in combination with gemcitabine (G), provides a significant survival benefit in metastatic pancreatic cancer. Rash, a common toxicity with EGFR inhibitors, has been proposed as a potential marker of erlotinib efficacy in multiple tumor types. The recent phase III study of GE ± bevacizumab (B) (Vervenne et al. ASCO 2008) provides a further opportunity to consider this topic. Methods: Chemo-naïve patients (pts) with metastatic pancreatic adenocarcinoma and KPS of 60–100 were randomized to GE-placebo (GE-P) or GE-B; pts received B/P 5mg/kg q2w plus E (100mg/d) and G (1,000mg/m2) given weekly for 7 weeks during the first 8-weekly cycle, followed by weekly for 3 weeks during subsequent 4-weekly cycles. Results: 607 pts were recruited; the arms were well balanced with respect to baseline characteristics. The addition of B to GE produced a significant benefit in PFS (hazard ratio [HR] 0.73, p=0.0002), and a trend towards longer OS (HR 0.89, p = 0.2087; median 7.1 mo vs 6.0 mo for GE-P). GE-B was well tolerated with no new safety signals observed. The incidence of rash was higher in the GE-B arm (73% vs 62% in the GE-P arm). There was a clear trend towards longer OS with increased grade of rash (see table ); this trend was apparent in both arms of the study. There was no difference in OS between treatment groups for any rash grade. Conclusions: The observed relationship between higher grades of rash and longer median OS supports the findings of the phase III PA.3 study of G ± E (Moore et al. JCO 2007), in pts with advanced pancreatic cancer. Studies are under way to prospectively investigate the relationship between rash and efficacy with erlotinib-based regimens in pancreatic cancer. [Table: see text] [Table: see text]
Planned interim analysis of the intergroup FFCD-GERCOR-FNCLCC-AERO phase III study comparing two sequences of chemotherapy in locally advanced or metastatic gastric cancers
Authors: Guimbaud R. , Bouché O. , Rebischung C. , Bonnetain F. , Louvet C. , Viret F. , André T. , Samalin E. , Gorent J. , Dutel J. , Bedenne L. 
Published: August 2020

4533 Background: There are several standard chemotherapies in locally advanced or metastatic gastric or cardia adenocarcinoma, including ECF. Methods: Patients (pts) with a gastric or cardiac adenocarcinoma, locally advanced or metastatic, not surgically curable, with a WHO PS ≤2 and evaluable or measurable lesions, were randomized (1:1) according to the following sequences: ECC (epirubicin 50 mg/m2 D1+ cisplatin 60 mg/m2 D1 + capecitabine 2000 mg/m2 D2 to D15, every 3 weeks) in 1st line, then FOLFIRI (IRI 180 mg/m2 D1, leucovorin 400 mg/m2 D1, bolus 5FU 400 mg/m2 D1 and continuous 5FU 2400 mg/m2 in 46h, every 2 weeks) in 2nd line (Arm A) vs the reverse sequence (Arm B) with a stratification for center, PS, adjuvant treatment, site, linitis and measurable disease. To show an improvement in median time to treatment failure for the 1st line (TTF: time between randomization and progression, or treatment discontinuation or recurrence or death) of 15 to 20 weeks for arm B (α bilateral 5%; β 20 %), 381 failures and 416 pts are required in 4-year period. An interim analysis is planned when at least 190 failures are observed (ITT). TTF is estimated according to the Kaplan Meier method and compared with a Log-rank test. Results: In arm A and B, 174 and 175 pts were included respectively, between 17/06/05 and 21/12/07. Pts characteristics are: PS 1: 51%, med. age 60 years, gastric 67%, M+ 88%, resected primary tumor 27% and linitis 23%. In arms A and B respectively, 141 and 147 pts received at least one dose in 1st line and 61 and 44 pts in 2nd line. Toxicities during the first line is more frequent in the ECC than in the FOLFIRI arm: grade 3/4 (88 vs 68% - p ≤0.0001) and grade 3/4 hemato toxicities (69 vs 36% - p ≤0.001). In 2nd line, toxicities frequency is not different in both arms. The median TTF in 1st line (n = 310 pts) is 4.7 months [3.8 - 5.7] for ECC and 5.2 months [4.4–6.0] for FOLFIRI (Log Rank p = 0. 78). Regarding the 252 failures observed (67% of the required events), the significance level to reject H0 is p = 0.012 (EAST V5). Conclusions: It is not possible yet to conclude to the superiority of FOLFIRI in 1st line; the final analysis after observation of 381 failures is required. Regarding toxicity, hemato-toxicity is more frequent with ECC in 1st line. [Table: see text]