bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact on therapeutic index of a chronomodulated infusion at conventional doses of oxaliplatin (OHP), 5-fluorouracil (5-FU) and folinic acid (AF) in not previously treated metastatic colorectal cancer patients: A multicentric observational study
Authors: Pirovano M. , Zambelli A. , Gherardi F. , Masseroni S. , Nasisi A. , Paraboni L. , Martignoni G. , Meregalli M. , Huscer C. S. , Tabiadon D. 
Published: March 2020

14572 Background: FOLFOX4 schedule represents the standard treatment for metastatic colorectal cancer in EU, but is characterized by relevant adverse effects like G3–4 neutropenia in 42 % of patients (data from MOSAIC study). Adjustment of chemotherapy delivery schedule to the circadian timing system allows a significative improvement of tolerability. Objective of this multicentric observational study is the evaluation of therapeutic index of a OHP and 5-FU + AF based schedule at the same doses of FOLFOX 4, but administered according to a chronomodulated schedule (FLOX-1). Methods: From November 2005 to December 2006, we treated 41 metastatic colorectal cancer patients (19 male and 22 female, average age 65) with OHP 85 mg/m2/d1q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 PM; 5-FU 1000 mg and AF 100 mg/m2/d1–2q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 AM: a total of 258 cycles (5.5 average for patient) were administered using Melodie infusional programmable system (138 cycles) and CIP preprogrammed disposable system (128 cycles), all in homecare regimen. These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. Results: Overall average dose intensity was 39.1 mg/m2/w for OHP and 907.5 mg/m2/w for 5-FU respectively. No G3-G4 haematological, hepatic and neurological toxicity were observed. ORR (CR+PR) was 41%. No patient has been treated with G-CSF. Conclusions: These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. No significant financial relationships to disclose.
Response to the combination of cetuximab, bevacizumab and irinotecan (cetux/bev/iri) in patients (pts) previously treated with 3rd-line panitumumab, following disease progression on oxaliplatin, irinotecan and a fluoropyrimidine
Authors: Tubb E. E. , Jacobs M. , Mitchell E. P. 
Published: March 2020

14586 Background: There are 2 monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) available for the treatment of advanced metastatic colorectal cancer- panitumumab, a fully human IgG2 kappa mAb and cetuximab, a chimeric IgG1 mAb. The ability to administer one agent after prior treatment with the other is unknown and further, not trivial given the possibility for cross-reactivity. In our institution, we evaluated an exploratory treatment schedule. Methods: We report the status of 8 colon cancer pts treated with panitumumab monotherapy as 3rd-line and subsequently treated with cetux/bev/iri as salvage chemotherapy. All were initially treated on 1 of 2 multicenter phase 2 studies enrolling pts on panitumumab; all pts had documented progressive disease (PD) during or after fluoropyrimidine and adequate doses of irinotecan and oxaliplatin, and low (1–9%) or high (=10%) EGFR tumor membrane staining by IHC. Pts received panitumumab 6 mg/kg q2weeks (wks) until PD or intolerability. Following PD they received bev 5 mg/kg and iri 250 mg/m2 q2wks and cetux 400 mg/m2, then 250 mg/m2 qwk. The endpoint was time to tumor progression (TTP). Results: The 8 pts (2 men, 6 women) were among those enrolled in 1 center. Median age was 67 years (range 51–81); 6 pts had low and 2 pts had high EGFR tumor expression. The median number of cycles of panitumumab was 8 (range 3–14); 1 had a partial remission (PR) for 24 wks, 4 had stable disease (SD) for a median of 14 wks (range 12–16) and 3 pts had PD. Following PD on panitumumab pts received cetux/bev/iri. The median number of cycles was 13 (range 2–17+); 1 had a PR of 20 wks, 6 had SD for a median of 20 wks (range 8–32+) and 1 pt had PD after 4 cycles. Median TTP was 24 wks (range 7–36+). Conclusion: In these 8 pts, prolonged TTP to the combination of cetux/bev/iri was observed following PD on panitumumab and standard chemotherapy. This combination may provide a potential treatment strategy for these heavily pretreated pts with advanced colon cancer. However, further investigation is needed. No significant financial relationships to disclose.
Yttrium-90 microsphere selective internal radiation treatment (SIRT) with concomitant chemotherapy (Chemo-SIRT) as first/second-line therapy in patients with colorectal cancer liver metastases
Authors: Pennington K. L. , Bruetman D. , Mesoloras G. , Hostetter R. , Gulec S. A. 
Published: March 2020

14589 Background: Yttrium-90 (Y-90) microsphere selective internal radiation treatment (SIRT) has been studied in patients (pts) with colorectal cancer liver metastases (CRCLM) in combination with FUDR and 5FU-LV with promising results. This is a phase II trial of SIRT and concurrent contemporary chemotherapy in the frontline management of CRCLM. Methods: Pts with metastatic disease limited predominantly to the liver were eligible for the study. Other entry criteria included KPS 70 or >, 3 month life expectancy and adequate marrow and renal reserve. Pre-treatment evaluations included the assessment of liver function, CEA level, 18F-FDG-PET/CT imaging, an angiogram and a 99mTc-MAA (macroagregate albumin) scan. SIRT with Y-90 resin microspheres (Sirtex Medical, Lake Forest, IL) was administered on day 2 of the first chemotherapy (Fol-Fox or Fol-Firi) course in either lobar or whole-liver fashion. Chemotherapy was repeated on a biweekly schedule. CEA levels and 18F-FDG-PET/CT based anatomic and functional volume (Vf) changes were used to determine tumor response at 4, 8, and 12 weeks after therapy. CTC v3 toxicity grades were used to classify adverse events. Results: 6 pts were treated as first-line and 2 pts as second-line. 5 pts received single lobe and 3 pts received whole liver treatment. Administered activity of Y-90 microspheres ranged from 0.9 to 3.1 GBq (mean 2.3 GBq). Mean tumor radiation absorbed dose was 203.6 Gy (Range 91.0–351.4 Gy). Mean liver absorbed dose was 47.8 Gy (Range 7.9–85.9 Gy). 6/8 pts had complete/near-complete metabolic response with a mean tumor Vf decrease in target lobe(s) of 98%). The remaining 2 pts demonstrated > 50% reduction in Vf in target lobe(s). A parallel decrease in CEA level was observed in responding pts. Surgical downstaging was attained in 3/8 pts. 2 pts developed grade III toxicity (one gastric ulcer and one alkaline phosphatase elevation). Conclusion: Chemo-SIRT as first-line therapy has a high level of response in CRCLM as measured by reductions in functional tumor volume and CEA level. Further follow-up of these pts is needed to confirm that this response is of clinical significance in terms of improved surgical downstaging and survival. [Table: see text]
A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)
Authors: Lee N. , Bae S. , Lee S. , Kim D. , Kim K. , Kim H. , Kim C. , Lee K. , Won J. , Hong D. , Park H. 
Published: March 2020

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.
Cetuximab and irinotecan in patients with colorectal cancer refractory to oxaliplatin and irinotecan
Authors: Gonzalez-Baron M. , Blanco M. , Feliu J. , Gómez C. , Casado E. , Castro J. , Belda-Iniesta C. , Garrido M. , Aguayo C. , Campos M. A. 
Published: March 2020

14600 Background: Patients with chemotherapy-resistant metastasic colorectal cancer have a poor prognosis with few therapeutic options. The purpose of this work is to evaluate the results of treatment with cetuximab and irinotecan in this group of patients. Methods: Between January 01 and July 06, 24 patients were treated in our centre with cetuximab. 19 patients received irinotecan 180 mg/m2 every two weeks with cetuximab at standard doses: 400 mg/m2 loading dose over 2 hours, then 250 mg/m2 over 1 hour weekly, and 5 patients received FOLFIRI schedule and cetuximab at the same doses as previously. Results: Characteristics of the 24 patients were: male/female 15/9; median age 63 years old (range 48–75); performance status 0–1 (10 patients), and 2–3 (14 patients). The median number of chemotherapy regimens preceding first cetuximab administration was 2 (range 1 to 4).12% had received one chemotherapy line, 64% two chemotherapy lines, 16% three chemotherapy lines and 8% received four chemotherapy lines. EGFR status was positive in all patients. The median of administrated cycles was 7.5 (range 2–26). There were 4 objective responses (16%; 95% CI: 5–38.5%) and 7 patients with stable disease (29%). The median progression free survival was 3.2 months and median overall survival was 7.8 months (95% CI: 3–14). The treatment was well tolerated. 6% of the patients had not cutaneous toxicity with the cetuximab treatment, 14 (25%) had a cutaneous toxicity grade 1 or 2 while 25% had a grade 3 or 4 toxicity, that lead to dose reduction in three cases and treatment drop out in one case. Other adverse effects with the treatment included four cases (17%) with diarrhoea grade 3, all of them in treatments with irinotecan, two patients (8%) suffered vomits grade 3, and one patient with grade 3 trombopenia. Conclusions: This therapeutic survey in an unselected population is in accordance with the results of the BOND survey for OS, tumour responses and toxicity. No significant financial relationships to disclose.
Does histology influence outcome in advanced oesophagogastric (OG) cancer? Individual patient data from 1,680 patients on three randomised controlled trials (RCT)
Authors: Chau I. , Starling N. , Cunningham D. , Oates J. , Iveson T. , Nicolson M. , Hawkins R. , Hickish T. , Seymour M. , Norman A. 
Published: March 2020

15001 Background: In advanced OG cancer, it is unclear whether squamous cell carcinoma (SCC) differs from adenocarcinoma (Ad) in its response to chemotherapy, as most phase III studies do not include both histology. The aim of this pooled analysis was to evaluate whether there is a differential chemotherapy effect on overall survival (OS), response rate (RR) and toxicity depending on tumour histology (SCC vs. Ad) using individual patient (pt) data. Methods: From 1994 to 2005, 3 RCTs were conducted assessing fluoropyrimidine ± platinum-based chemotherapy. This analysis was restricted to eligible pts with SCC or Ad histology who received =1 dose chemotherapy. Apart from OS and RR, a toxicity composite endpoint (TCE) was constructed - defined as occurrence of grades =3 diarrhoea, (febrile) neutropenia, infection, nausea & vomiting, grades =2 renal and neurotoxicity. Ad was used as the control group. Two-sided p values of <0.05 were considered significant. Results: Of the 1,836 pts randomised, 1,680 were included for this analysis of whom 1,536 (91%) had Ad and 144 (9%) had SCC. Locally advanced disease was present in 17% and 20% of Ad and SCC patients respectively. The median survival was 9.4 months with Ad and 7.7 months with SCC and one year survival rates were 38% and 29% respectively (log rank p= 0.115) and this remained non- significant on multivariate analysis (p=0.206). The RR was 40.4% (95% CI: 38–42.9%) in Ad and 33.3% in SCC (95% CI: 26.1–41.4%; p=0.109). TCE occurred in 45% and 44% of patients with Ad and SCC respectively (p=1.0). Time to TCE was not significantly different (log rank p=0.829). Conclusions: Although there was a trend towards worse survival with SCC, no significant differences in chemotherapy outcome were demonstrated, despite our large dataset. Molecular therapeutics targeting distinct biological pathways between the two histology subtypes may influence outcome more than cytotoxic combinations in the future. No significant financial relationships to disclose.
Phase II trial of continuous/metronomic 5-fluorouracil infusion plus long acting Octreotide in advanced neuroendocrine carcinoma
Authors: Dogliotti L. , Brizzi M. P. , Ferrero A. , Milanesi E. , Ciuffreda L. , Castiglione F. , Bombaci S. , Perroni D. , Alabiso O. , Berruti A. 
Published: March 2020

15003 Background: The administration of cytotoxic drugs on a metronomic schedule has shown antiangiogenetic properties. Well differentiated neuroendocrine carcinomas are notoriously highly vascularized and may be responsive to metronomic chemotherapy. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion in association with and long-acting release (LAR) octreotide in patients with advanced/metastatic neuroendocrine carcinoma. Patients and Methods: Twenty-nine patients (pts), with metastatic or locally advanced well differentiated neuroendocrine carcinoma not amenable to surgery with radical intent and not previously submitted to systemic treatments were enrolled. Treatment consisted of 5FU intravenous continuous infusion (200 mg/m2 daily) in association with Octreotide LAR (20 mg once every 4 weeks). 5FU treatment was administered until progression or for a maximum of 9 months. Octreotide LAR was administered until progression. Patients were followed for toxicity, objective response, symptomatic response, biochemical response, time to progression and survival. Results: According to RECIST criteria a partial response was observed in 7 patients (24.1%), a stable disease in 20 pts (69.0%) and a progression disease in only 2 pts (6.9%). A biochemical (chromogranin A) response was observed in 11/25 assessable patients (44.0%), 9/15 symptomatic patients (60.0%) obtained symptom relief. Post-treatment surgery was attempted in three patients, one of them was radically resected. The median time to disease progression was 25 months (range 2–69 months), median overall survival was not reached. Hematologic toxicity was rare and mild [grade 2 neutropenia in 2 pts (6.9%)]. Six cases (20.7%) suffered from grade 2–3 hand-foot syndrome. No patient withdrew from the study because of adverse events. Conclusions: Continuous/metronomic 5FU infusion plus octreotide LAR is well tolerated and shows promising activity in patients with advanced well differentiated neuroendocrine carcinoma. Additional studies with this combination are warranted. No significant financial relationships to disclose.
A phase I study of the addition of weekly oxaliplatin to weekly gemcitabine during radiotherapy for unresectable pancreatic or biliary malignancies
Authors: O’Neil B. H. , Blackstock A. W. , Goldberg R. M. , Shearer H. , Sanoff H. K. , Aklilu M. , Bernard S. , Martinie J. , Kim H. J. , Tepper J. E. 
Published: March 2020

15008 Purpose: Locally advanced pancreatic cancer (LAPC) leads to a poor survival, and current therapies are inadequate. External beam radiotherapy (EBRT) has been used to obtain local control, but the most effective systemic agent, gemcitabine(gem), can be used only at low doses with standard RT. Oxaliplatin (ox) has activity in PC, and has been delivered safely at doses near full systemic doses with EBRT for rectal cancer. We set out to define the maximum tolerated dose (MTD) of ox in combination with gem + upper abdominal EBRT. Methods: Patients (pts) with LAPC or biliary ca were eligible. Prior systemic therapy was allowed. A 3 + 3 design was employed with 4 dose levels (table). Gem + ox was given once weekly. EBRT was given in 1.8 Gy fractions to 50.4 Gy using a multi-field technique. DLT was defined as any grade 4 tox or grade 3 tox resulting in treatment delay > 1 wk. Results: 11 pts have completed therapy (Table). 10 pts had LAPC, 1 had ampullary ca. No pts in the first 2 cohorts had DLT. Pt #3 in cohort 3 had DLT (grade 3 elevated liver enzymes). Cohort 3 was expanded; patients 4 and 5 in the cohort have completed therapy without DLT; pt 6 is not yet evaluable. To date, 43 grade 3 toxic events have occurred in 11 evaluable patients. No grade 4 toxicities have occurred. The most common grade 3 tox are: nausea (63%), metabolic (54%), hyperglycemia (45%), neutropenia (36%), vomiting (27%). SD was best radiographic response in 8 of 8 evaluable pts. One patient with ampullary ca had regression of disease from vessels and was resected, but had positive retroperitoneal margin and died of a post-operative complication. Five pts have died (OS 2.6–12.2 mos). Median OS is currently 9 mos (95% CI 4.6, 12.3). Conclusions: Weekly oxaliplatin can be given safely with weekly gemcitabine (200 mg/m2) during EBRT for LAPC. The ox MTD in this combination is not yet defined, but is at least 30 mg/m2 weekly. Final dose results and updated efficacy results will be presented at the meeting. [Table: see text] [Table: see text]
Recent advances in the surgical treatment for esophageal cancer in Japan: An experience of 1000 cases who underwent an esophagectomy at a single institute
Authors: Morita M. , Yoshida R. , Ikeda K. , Honboh T. , Ohta M. , Egashira A. , Oki E. , Sadanaga N. , Kakeji Y. , Maehara Y. 
Published: March 2020

15011 Background: Most cases of esophageal cancer are squamous cell carcinoma in Japan and the prognosis of such patients tends to be poor. However, the clinical results after an esophagectomy have recently been reported to improve. Methods: The mortality and morbidity as well as the patients’ prognosis were evaluated in 1000 cases of esophageal cancer who all underwent an esophagectomy in the Department of Surgery and Science (Department of Surgery II), Kyushu University, Japan from 1964 to 2006. The incidence of squamous cell carcinoma was 94 %. The patients were divided into three groups according to the operation period: Group I (n=197), Group II (n=432), and Group III (n=371) underwent an esophagectomy during the periods of ‘64-’80, ’81-’93, and ’93-’06, respectively. The incidences of TNM Stage 0 or I gradually increased (4, 19 and 24 %, respectively), while those of Stage IV decreased (28, 19 and 14 %). Results: The 5-yr overall survival rates (OSR) and cause-specific survival rate (CSR) after an esophagectomy for all 1000 cases were 30 and 37 %, respectively. The 5-yr OSRs of Groups I, II and III were 14, 27 and 46 %, while the 5-yr CSRs were 18, 36, and 52 %, respectively (P<0.01 between each group). When the prognoses were compared for each TNM stage, an improvement in the prognosis was observed at every tumor stage. A multivariate analysis (Cox proportional hazard model) revealed not only the age, depth of invasion, node metastasis, curability (each P<0.001) and extent of a lymphadenectomy (P<0.05) but also the operation period (P<0.001) to be independent prognostic factors. The morbidity rates of Groups I, II and III were 62, 38, and 33 %, and the incidences of pulmonary complications were 42, 13 and 14 %, respectively (P<0.01, Group I vs. II and I vs. III). The 30-day mortality rates were 8.1, 2.1 and 0 %, respectively (P<0.01 between each group). Conclusions: An analysis of a total of 1000 cases with esophageal cancer revealed that an esophagectomy has generally been safely performed without any critical pulmonary complications, while an increasingly favorable prognosis has been achieved due to recent advances in surgical techniques and treatment modalities. No significant financial relationships to disclose.
A phase II breast cancer chemoprevention study of lovastatin in high-risk women: Initial feasibility data
Authors: Kurian A. W. , Sharma V. B. , Schwartz E. J. , Mills M. A. , Staton A. D. , Chun N. M. , Kingham K. E. , Ford J. M. 
Published: March 2020

1502 Background: More than 250,000 U.S. women have high inherited breast cancer risk; many develop hormone-receptor negative (ER/PR-) tumors, for which no chemoprevention exists. Pre-clinical data suggest that hydrophobic HMG-CoA reductase inhibitors (statins) may reduce risk of ER/PR- breast cancers. We report initial feasibility results of a phase II study of lovastatin for breast cancer chemoprevention. Methods: Study Design: Single-arm, non-randomized phase II study. Agent: Lovastatin 80 mg daily for 6 months. Primary Endpoint: Change in proportion of women with atypical cytology on 2-quadrant random periareolar fine needle aspiration (rpFNA) of breast duct cells before and after lovastatin. Secondary Endpoints: Changes in Ki-67, ER/PR, and elevated levels of oxidative DNA damage (ODD) measured by single-cell gel electrophoresis (Comet) assay of breast duct cells; changes in mammographic density; breast cancer incidence. Eligibility: BRCA1/2 mutation carrier, or estimated lifetime risk = 20% due to family history. Statistical Considerations: Planned sample size of 60, yielding 90% power to detect 50% change in proportion with atypia. Results: Twenty participants enrolled in Year 1; 15 have pre-study rpFNA and 5 have post-study rpFNA results to date. Pre-Study Cytology: N=15: 1 (7%, 95% confidence interval 0–32%) had insufficient, 11 (73%, 48–90%) had normal, and 3 (20%, 6–46%) had atypical cytology. Pre-Study Comet Assay: N=4 to date, 2 with atypical and 2 with normal pre-study cytology: 2 with atypical cytology (100%, 29–100%) had a positive Comet assay for elevated ODD, but 0 with normal cytology (0%, 0–71%) had a positive Comet assay. Post-Study Cytology: N=5, 1 with atypical cytology pre-study: 5 (100%, 51–100%) were normal post-study. Post-Study Comet Assay: N=1 to date, with atypical cytology and positive Comet assay pre-study: cytology was normal and Comet assay negative post-study. The study has been well-tolerated, with no drop-out. Conclusions: An early-stage chemoprevention study of lovastatin for 6 months, including 2 rpFNAs, appears feasible in high-risk women. Early results suggest a correlation between cytologic atypia and elevated levels of ODD, and the possibility that lovastatin might reverse these abnormalities. Accrual is ongoing. No significant financial relationships to disclose.