bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metronomic irinotecan and standard FOLFIRI regimen as first-line chemotherapy in metastatic colorectal cancer (MCRC). Final results of phase II study
Authors: Nardi M. , Azzarello D. , Del Medico P. , Giannicola R. , Falzea A. , Giuffrè C. , Maisano R. , Panuccio V. , Raffaele M. , Zavettieri M. , Avallone A. 
Published: March 2020

14520 Background: Angiogenesis is necessary to sustain the growth of both the primary tumour and the development of metastases in colorectal cancer. Before the clinical use of bevacizumab, metronomic chemotherapy was the only mean to block the growth of tumor microvessel. CPT-11 showed, in preclinical model, to have antiangiogenetic properties using low doses and weekly administration. We carried out this study in order to evaluate the activity and toxicity of mixed metronomic and standard FOLFIRI regimen in MCRC. Methods: From 10/03 to 9/05 we treated 46 pts (24M 22F), median age 66 years (range 41–79), ECOG PS 0–2 with this schedule: CPT- 11 10 mg/mq days 1, 7, 10 and CPT-11 150 mg/mq day 2, l-Folinic Acid 100 mg/mq days 2 and 3, 5-FU 400 mg/mq bolus days 2 and 3 and 5- FU 600 mg/mq 44 hours c.i. days 2 and 3 every two weeks for a maximum of 12 cycles. Results: All pts have been evaluable activity and toxicity. We obtained 9 CR (20%), 12 PR (26%) with an ORR of 46% (CI 95%: ±13%) and 17 SD. After a median follow-up of 24 months we registered a median TTP of 10 months and a median OS of 22 months. As regard toxicity, the chemotherapy has been well tolerated; no toxic deaths occurred and no therapy ended for toxicity. 6 pts had 25% dose reduction (standard schedule) for diarrhea G4 after the first cycle. The main toxicities recorded on a total of 440 cycles (cy) delivered were: diarrhea G4 1.7% and G3 2.3% of the cy. Neutropenia G3 5.8% and vomiting G3 0.5% of the cy. Anemia G2 was recorded in 14 pts. All pts suffered from partial alopecia and half of the pts from mild oral mucositis. Conclusions: This mixed schedule seems to be active and well tolerated, ORR, TTP and OS are similar to Hurwitz results (NEJM 2004; 350: 2335–42) but with less adverse events. The combination of this schedule with bevacizumab deserves further studies. No significant financial relationships to disclose.
A randomised, placebo-controlled, double-blind phase II study of raltitrexed and gefitinib vs raltitrexed alone as 2nd line chemotherapy in subjects with advanced colorectal cancer (CRC). GON group study (Grupo Oncologico del Norte)
Authors: Vieitez J. , Valladares M. , Pelaez I. , Gonzalez-de-Sande L. , García-Girón C. , García-López J. , Jimenez-Lacave A. , Reboredo M. , Bovio H. , Garcia-Foncillas J. 
Published: March 2020

14523 Background: Second-line monotherapy activity in patients with metastatic CRC is low with an objective response rate of 9% in phase II-III studies (Viéitez et al, Am J Clin Oncol 2003; Rougier y cols., 1998). Gefitinib has shown activity in vitro and in animal models against colon cancer cell lines, and has shown to increase the activity of raltitrexed (Cardiello et al, Clin Cancer Res 2000). Methods: A multi-center randomized, double blind, phase II study was initiated in patients with metastatic CRC who failed prior therapy based on 5-FU LV plus OXL or/and CPT and measurable disease. Patients were randomized to received Raltitrexed, 3 mg/m2 IV q3w, (arm A) or Raltitrexed plus Gefitinib, 250 mg PO OD (arm B). Primary end-point was time to progression (TTP); Secondary end-point was objective tumour response rate (ORR) based on the RECIST criteria at six month, overall survival (OS) and safety. Results: Between Dec 2003 and Oct. 2005, 76 patients were recruited in 7 centers. Median age was 65.0 (range 75–31) and 63.5 (range 76–40) years for arm A and B respectively; demographics characteristics were well balanced between both arms including sex, race or other previous mayor conditions. Both treatment arms were well tolerated. Grade 3/4 toxicity in Arm A was: anorexia 10.5% (4), asthenia 10.5% (4), liver toxicity 10.5% (4), nausea 5.3% (2), diarrhea 5.3% (2), abdominal pain 2.6% (1), neutropenia 2.6% (1), thrombopenia 2.6% (1), renal failure 2.6% (1). Grade 3/4 toxicity in Arm B included: anemia 2.6% (1), liver toxicity 7.9% (3), diarrhea 5.3% (2), skin rash 2.6% (1), melenas/upper digestive bleeding 2.6% (1), fever 2.6% (1). ORR was 5.3% (2/38) (95%CI: 0.64–17.75) and 7.9% (3/38) (95%CI: 1.66–21.38) for arm A and B. Median TTP was 72 (95%CI: 59–132) and 63 (95%CI: 57–84) days; median OS was 291 (95%CI: 255–539) and 361 (95%CI: 283–533) days; and median duration of treatment was 74.5 (range 21–274) and 63.5 (range 12–324) days for arm A and B. Conclusions: Addition of Gefitinib to Raltitrexed in pretreated patients with advanced CRC is well tolerated, with manageable toxicity profile, but not increases Raltitrexed efficacy. No significant financial relationships to disclose.
Prognostic importance of primary tumor resection in patients with advanced colorectal cancer (CRC): A Canadian province’s experience
Authors: Ahmed S. , Shahid R. , Ahmad I. , Alvi R. , Yadav S. , Sami A. , Arnold F. , Popkin D. , Haider K. 
Published: March 2020

14529 Background: Surgical resection (SR) of primary tumor in patients with newly diagnosed advanced CRC remains controversial. Limited data is available regarding potential benefit of resection in these patients. We performed a population-based study to determine the prognostic value of SR of primary tumor in patients with metastatic CRC. Methods: Medical records of patients with metastatic CRC diagnosed between 1991–2000 in the province of Saskatchewan were reviewed. Patients with unresectable T4M0 disease were excluded. A multivariate analysis was performed using Cox regression model and various clinicopathologic variables were tested for their prognostic significance. Kaplan-Meier curves were used to determine survival. A preliminary analysis of data of 212 eligible patients diagnosed between 1998–2000 is presented here. Results: Patients median age was 71 yrs (33–94) and M:F was 1:0.77. One hundrad thirty one (62%) patients underwent SR for the primary tumor. Among 131 patients, 76 (58%) were operated for tumor related symptoms (36% obstruction, 14% perforation, and 9% bleeding). Six percent patients died of postoperative complications. Of 212 patients, 36% received 5FU-based chemotherapy (46% patients with SR) and 17% received a second line therapy. Median overall survival (OS) of all patients was 6.7 months. Patients who underwent SR of primary tumor had a significantly better median OS of 11 months compared with 3 months in patients who did not have surgery (HR 0.47; 95% CI 0.29–0.76). Patients who underwent SR and had received chemotherapy had a median OS of 14.8 months compared with median OS of 6 months if they did not receive chemotherapy (HR, 0.29; 95% CI 0.15–0.55). In addition to 5FU-based chemotherapy and SR of primary tumor; metastectomy, age >65 yrs, elevated alkaline phosphatase level and thrombocytosis were other important variables that were correlated with survival in patients with advanced CRC. Conclusions: SR of primary tumor has been associated with significant improvement in survival independent of systemic chemotherapy in patients with advanced CRC. Further analysis of data in patients diagnosed between 1991–2000 is planned to confirm these findings in a larger group of patients. No significant financial relationships to disclose.
Effect of hyperthermia on the pharmacokinetic profile of oxaliplatin administered by intraperitoneal route in rats
Authors: Piche N. , Leblond F. , Sideris L. , Leblanc G. , Leclerc Y. E. , Pichet V. , Dube P. 
Published: March 2020

14535 Background: Whereas in vitro studies have demonstrated that hyperthermia enhances the cytotoxicity and tissue penetration of oxaliplatin, in vivo studies conducted so far have failed to document clearly such effect in the context of heated intraperitoneal chemotherapy. The purpose of this study is to assess the effect of heat on the pharmacokinetic profile of oxaliplatin administered intraperitonealy in rats. Methods: Under general anesthesia, 25 Sprague-Dawly rats of 258 g (235–440 g) were submitted to 3 different doses of intraperitoneal oxaliplatin (460, 920 and 1840 mg/m2) at 3 different temperatures of perfusion (37, 40 and 43Â°C) during 25 minutes. At the end of perfusion, samples in different compartments were harvested for dosage of oxaliplatin concentration: 2 ml of perfusate, 1 ml of portal blood, 1 ml of systemic blood, 100 mm3 of parietal peritoneum and 100 mm3 of mesentery. Dosage of oxaliplatin was performed by high performance liquid chromatography. Results: We observed a linear and proportional correlation between the concentration of oxaliplatin in the perfusate and the concentration of oxaliplatin for all compartments (R2 : 0.9833 for systemic blood, 0.9874 for portal blood, 0.9053 for parietal peritoneum and 0.9999 for mesentery). Regarding the effect of temperature, we observed a linear and proportional correlation of heat on the concentration of oxaliplatin in parietal peritoneum (R2 : 0.8543), no effect on mesentery (R2: 0.1371) and a tendency of heat to limit concentration of oxaliplatin in portal and systemic blood (R2 = 0.0994 and 0.5854 respectively). Conclusion: Heat improves the absorption of oxaliplatin into the peritoneal cells and seems to limit the systemic absorption of oxaliplatin, the latter observation suggesting a decrease in systemic toxicity. These are two strong arguments supporting the use of oxaliplatin by intraperitoneal route, as it is currently done in the human treatment of peritoneal carcinomatosis from colorectal origin. No significant financial relationships to disclose.
Autoimmunity predicts prolonged survival in colon cancer patients undergoing GOLFIG biochemotherapy
Authors: Correale P. , Tagliaferri P. , Montagnani F. , Remondo C. , Intrivici C. , Fulfaro F. , Tsang K. Y. , Tassone P. , Rotundo M. S. , Venuta S. , Francini G. 
Published: March 2020

14542 Background: A multi-center phase II trial has been designed to evaluate toxicity, anti-tumour and immune-biological activity of the bio-chemotherapy GOLFIG regimen in advanced colorectal cancer (A-CRC). Methods: The trial involved 46 patients (34/46 2nd line or more). The biweekly GOLFIG regimen consisted of gemcitabine (1,000 mg/m2, day 1), oxaliplatin (85 mg/m2, day 2), levofolinic acid (100 mg /m2, day 1,2) and 5-FU (400 mg/m2 as a bolus, and 800 mg/m2 as 24 hour infusion, days 1,2) followed by sc GM-CSF (100 μg, days 3 to 8) and sc IL-2 (0.5 X 106 IUs twice a day, days 9 to 14). Results: GOLFIG regimen was well tolerated and resulted very active (ORR = 56.5%; disease control = 91.3%), fulfilling the pre-selected (40–60%) target of activity, with a promising TTP [12.26 months, 95% CI; 9.2–15.2 mo.] and OS [18.76 months, 95% CI; 15.2–22.3 mo.]. We detected a significant rise in lymphocyte number and colon cancer-specific cytotoxic T cells (CTLs) paralleled by a reduction in suppressive T-regulatory CD4+CD25+ FoxP3+ lymphocytes -Treg. Self-limiting autoimmunity (AI) occurred in 6 (14%) patients. 1 patient developed cutaneous lesions, with pathological diagnosis of Discoid Lupus Erythematosus (DLE), while 5 other presented a mono / oligoarticular arthritis mainly localized at the knees, elbows, shoulders and fingers with signs of synovitis (pain and swelling) paralleled by a significant increase of inflammatory markers (ESR, C-RP and rheumatoid factor). Subgroup analysis disclosed a mean time to progression of 23.8 months (95% CI; 12.1–35.56 mo.) and an overall survival of 31.83 months (95% CI; 19.9–43.7 mo.) in the 6 AI patients, significantly longer than in patients who did not develop AI [TTP and OS respectively 10.52 (95% CI; 7.7–13.3) and 16.8 months (95% CI; 13.3–20.2)], P ≤ 0.0039 and 0.0080. 5/6 AI patients are still alive and 3 have so far achieved a survival of 37, 41 and 50 months. Conclusions: The GOLFIG regimen exerts immunological and anti-tumour activity and has manageable toxicity in A-CRC. The occurrence of AI is predictive of a favourable outcome. These results provided the rationale for a presently ongoing phase III trial aimed to compare the efficacy of GOLFIG vs. FOLFOX-4 regimen as first line treatment in A- CRC patients. No significant financial relationships to disclose.
Phase II comparative study of capecitabine combined with oxaliplatin (XELOX) and CPT-11 (XELIRI) for advanced colorectal cancer patients (p) previously treated with 5-FU-based chemotherapy
Authors: Manzano J. L. , Díaz N. , Rolfo C. , Juez I. , Gracía-Bueno J. M. , González M. L. , Queralt B. , Losa F. , Martín C. , Abad A. 
Published: March 2020

14544 Background: Based on the results obtained with Capecitabine (XEL), Oxaliplatin (OX), and CPT-11 (IRI), we proposed this exploratory study to asses the efficacy of XELIRI and XELOX, for advanced colorectal cancer, after a first line treatment with 5 FU plus OX (FOLFOX) or IRI (FOLFIRI). Methods: P aged = 18 with histological diagnosis of metastatic colorectal adenocarcinoma, were assigned to XELOX arm (XEL, 1000 mg/m2 BID during 14 d; OX, 130 mg/m2 d1; q3w) or XELIRI arm (XEL 1000 mg/m2 BID during 14 d; IRI 240 mg/m2 d1; q3w), depending on previous treatment (FOLFIRI or FOLFOX, respectively). Although sample size was calculated for 115 p, recruitment was premature closed due to the low inclusion rate related with cetuximab + IRI approval for second line treatment. Results: Forty three p (25 p, XELOX; 18 p, XELIRI) were enrolled: median age 63.2 years; M/F, 40.5%/59.5%; ECOG PS 0–1, 79.1%. All p have been previously treated for metastatic disease and 65.1% had stage IV. Main sites of metastatic disease were liver (71.8%), lymph nodes (7.7%), pelvis (7.7 %) and lung (5.1%). XELOX/XELIRI treatment data: total number of administered cycles was 94/85 and median relative dose intensity 100%(XEL)/99%(OX) and 96%(XEL)/94%(IRI); disease control rate (PR+SD) was 28%/33.3%, median TTP 3.4/4.1 months, median OS 10.3/11.2 months and 1-year survival, 39.1%/44.3%, respectively. Twenty p (46.5%) received further antitumoral treatment. Most frequent G3–4 toxicities per p are detailed in table 1 . Conclusions: Capecitabine based combinations show an excellent toxicity profile and good efficacy results, in terms of disease control and survival rates, for advanced colorectal cancer patients previously treated with 5-FU schedules. [Table: see text] No significant financial relationships to disclose.
A study for establishment of individualized chemotherapy for colorectal cancer based on the individual 50% inhibitory area under the concentration curve (AUCIR50) using the collagen gel droplet embedded culture-drug sensitivity test (CD- DST)
Authors: Ochiai T. , Nishimura K. , Watanabe T. , Kitajima M. , Konishi N. , Sato G. , Futagawa S. , Nagaoka I. 
Published: March 2020

14553 Background: The drug sensitivity of tumor cells is one of the key issues to explore in individualized 5-fluorouracil (5-FU) based chemotherapy for colorectal cancer patients. We reported that growth inhibition rate (IR) and area under the concentration curve (AUC) approximated to a logarithmic curve using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) in ASCO 2003 (#1283). We also reported that the individual 50% inhibitory area under the concentration curve (AUC IR50) could be obtained using the individual AUC-IR curve in ASCO 2006 (#13560). The aim of this study was to evaluate the achievement of the individual AUCIR50 in 5-FU based adjuvant chemotherapy for the establishment of individualized chemotherapy. Methods: Surgical specimen was obtained from resectable 33 CRC patients without any preoperative chemotherapy during 2001 to 2005. 5-FU based adjuvant chemotherapy was administered in all patients. CD-DST was performed under 6–9 different conditions. The individual AUCIR50 was obtained from the individual AUC-IR curve. The patients were divided into 2 groups, the achieved group and the non-achieved group. In the achieved group, total administered AUC was more than the individual AUCIR50 and in non-achieved group, the total administered AUC was less than the individual AUCIR50. Recurrence rates were evaluated from the 2 groups. Results: In all patients, the recurrence rates were 6.7% (1/15) in the achieved group and 27.8% (5/18) in the non-achieved group. In the colon cancer patients, the recurrence rates were 8.3% (1/12) in the achieved group and 10.0% (1/10) in the non-achieved group. In the rectal cancer patients, the recurrence rates were 0% (0/3) in the achieved group and 50.0% (4/8) in the non-achieved group. Conclusions: The recurrence rate of the achieved group was lower than that of the non-achieved group. Therefore, this study demonstrated that the achievement of the individual AUCIR50 could be a prerequisite of individualized 5-FU based adjuvant chemotherapy. No significant financial relationships to disclose.
Hepatic artery triplet chemotherapy for liver metastases from colorectal cancer
Authors: Levi F. , Adam R. , Innominato P. , Giacchetti S. , Castaing D. , Hauteville D. , Kunstlinger F. , Li X. M. , Machover D. , Bouchahda M. 
Published: March 2020

14554 Background: Chronomodulated (Chrono) irinotecan (I), 5-fluorouracil (F), leucovorin and oxaliplatin (O) offered sustained tumor control in CRC patients (pts) failing several chemo (Gholam et al. The Oncologist 2006). The relevance of Chrono IFO as hepatic artery infusion (HAI) for long term outcome was investigated in CRC pts with liver metastases. Methods: 32 heavily pretreated non hospitalized CRC pts received 5-day (d) q21 d courses (c) with d1 I (160 mg/m2 from 2 to 8 am, peak at 5 am) and d2–5 F (600 mg/m2/d from 10 pm to 10 am, peak at 4 am) and O (20 mg/m2/d from 10 am to 10 pm, peak at 4 pm). Intravenous cetuximab was also given to 3 pts. 172 courses (c) were given (median, 5; 1–15) using a multichannel pump (Mélodie, Aguettant, F). Toxicity was assessed q21 d and response q3 c with CT scan. Results: Prior chemo lines 1/2/3/4+: 3/5/10/14 pts; WHO Performance Status 0/1/2/3: 14/11/6/1 pts; median age: 63 years (32–73); liver only: 25 pts; liver and lung: 7 pts. Treatment was withdrawn for thrombosis (7 pts, 21%) and/or Grade (G) 3 abdominal pain (4 pts ). G3–4 diarrhea occurred in 6 pts (12%). G3–4 leucopenia, anemia and thrombocytopenia were respectively found in 5, 2 and 1 pt. G3 sensory neuropathy occurred in 3 pts with similar G at baseline. 3 pts displayed alopecia. Of 29 pts with measurable lesions, disease progressed in 12 pts (exclusively outside the liver for 4 pts) and was controlled in 17 pts (58%), including 10 objective responses - 34% [95% C.L. 13.4 to 50.6]. Partial hepatectomy was performed in 4 pts with measurable disease (14%): R0 (3 PR) and R1 (1 SD). Median Progression free survival (months, m) is 5 m [1.9 to 8.0] and median survival is 18.4 m [9.9 to 26.9], with 6 pts alive at 2.9 to 63 m. Conclusions: Triplet chronoHAI is safe in heavily pretreated pts and achieves consistent activity against CRC liver metastases despite prior failure on the same 3 drugs. The combination of systemic cetuximab with triplet HAI is feasible and could prevent extra hepatic dissemination, a hypothesis to be soon tested in a prospective European trial. Supported by ARTBC, Hôpital P. Brousse, Villejuif, France. No significant financial relationships to disclose.
Clusterin in stool: A new diagnostic marker of colorectal cancer
Authors: Pucci S. , Sesti F. , Mazzarelli P. , Bonanno E. , Spagnoli L. G. 
Published: March 2020

14561 Background: Colon cancer is second only to lung cancer in men and to breast carcinoma in women, for incidence and mortality in western countries .The higher incidence per age is observed between the sixth and seventieth decade, while 60% of the patients survive up to five years. The most important reason for the low percentage of recoveries is due to the fact that when the primary tumour is removed, a high number of patients have already developed micro-metastases, principally at liver. Therefore, methods for early screening are requested. Molecular markers have emerged as an important strategy to evaluate the individual susceptibility for cancer insorgence and for clinical cancer therapy. Recent studies have demonstrated an increase in clusterin expression in breast carcinoma suggesting a possible role of this protein in tumour progression. Clusterin is an heterodimeric (a and β chains) ubiquitous glycoprotein implicated in a large number of physiological processes and in the control of cellular proliferation. Despite the original hypothesis that clusterin is a marker for programmed cell death, several experiments and clinical studies have demonstrated conflicting findings on its role in tumors. Methods: We have studied clusterin isoforms expression in tumour progression, in particular in the adenoma-carcinoma sequence of colorectal cancer. Results: the observation of 35 samples of human intestinal mucosa, such as endoscopic biopsies and surgical specimens, demonstrated that the progression towards high grade and metastatic colon carcinoma leads to a pattern shift of clusterin isoforms production, the complete loss of the proapoptotic nuclear form and an over expression of cytoplasmic secreted form correlateting to a phenotype with high metastatic potential. Moreover we observed in tumor biopsies the release of clusterin in the crypts lumen. The ELISA immuno-dosage of clusterin demonstrated that the sclusterin overexpression in tumours correlates to a significant increase of clusterin in the serum and stools of patients affected by tumoural pathologies and in particular by colorectal cancer. Conclusions: These data suggests a new role of secreted clusterin as a new diagnostic circulating marker and a potential new therapeutic target. No significant financial relationships to disclose.