bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of neoadjuvant chemoradiotherapy with capecitabine and weekly irinotecan followed by laparoscopic mesorectal excision
Authors: Ugidos L. , Conill C. , Delgado S. , Gines A. , Gallego R. , Ayuso J. R. , Miquel R. , Lacy A. M. , Castells A. , Maurel J. 
Published: March 2020

14556 Background: To establish the feasibility and efficacy of capecitabine with weekly irinotecan (CAPIRI) and concurrent radiotherapy (RT) in patients with locally advanced and resectable metastatic rectal cancer, followed by LAME. Methods: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (us), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m2 (days 1,8,15,22,29) and two doses of capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m2 bid; DL II 375 mg/m2 bid; DL III 500 mg/m2 bid, according to phase I methodology. Conformal radiotherapy was administered up to a total dose of 45 Gy/1.8 Gy per fraction. LAME was planned 5–7 weeks after CRT. Results: From January 2003 to March 2006, 22 patients (three with potentially resectable metastatic disease) were included. Median age was 62 (range 48 to 78). 6 pts were usT3N0 and 16 pts usT3–4N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 or 4 adverse events were observed in all levels; DL I asthenia (1p); DL II diarrhea (2p) and DL III asthenia and neutropenia (1p), diarrhea (1p) and hyperbilirrubinaemia (1p). All patients except one who refused treatment after 1 week therapy (DL I), completed CRT and underwent surgical resection (R0 81%, R2 19%). Abdominoperineal resection was done in two cases (9%). Conversion rate to open surgery was 5%. Median hospital stay was 7.9 days. The overall postoperative morbidity was 4.7%. Median excised nodes were 11 (range 4–21). Pathological complete response was observed in two patients (9%), both of them in DL III. With a median follow-up of 25 months (range 9–46), disease free survival and overall survival was 67% and 95% respectively. Conclusions: Preoperative CRT with CAPIRI is feasible, but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published. LAME after CAPIRI had short oncologic outcomes comparable with open mesorectal excision. No significant financial relationships to disclose.
Individualizing the interval between neoadjuvant chemoradiation with uracil-tegafur (UFT) and total mesorectal excision in magnetic resonance imaging (MRI) defined poor-risk rectal cancer
Authors: Sizer B. , Arulampalam T. , Austin R. , Basu D. , Lacey N. , Menzies D. , Motson R. 
Published: March 2020

14557 Background: The importance of achieving negative circumferential resection margins (CRM) for patients (pts) with MRI - defined poor - risk rectal cancer (PRRC) has led to an increase in the use of pre-operative chemoradiotherapy (CRT) employing long fractionation schedules, usually with an interval of 4 to 6 weeks before surgery. We report our experience of using serial MRI post CRT to optimise the timing of total mesorectal excision (TME) surgery at maximal radiological response for each pt. Methods: Data was collected prospectively from 4/03 to 10/06 on toxicity and response for 50 consecutive patients ( 36 male; median age 64 years, range 39 - 76 years), 47 with biopsy - proven PRRC by MRI criteria (threatened / definite CRM involvement, T3 > 5mm into perirectal fat, T4 tumours, and / or multiple nodes) and 3 pts with localised recurrence after previous anterior resection. Pts received 2 phase, conformal external beam radiotherapy ( 45 - 50.4 Gy / 25 - 28 fractions / 5 weeks), concurrently with their choice of either oral UFT (n = 44, 88%), 240mg/m2/d d 1 - 28 with Leucovorin (LV) 90mg/d or iv bolus 5 FU (n= 6) 300mg/m2 d 1,8,15,22,29 with LV 20 mg/m2). Clinical re-assessment q 2 wkly from 4 weeks post CRT, with serial MRIs 4-weekly, from 6 wks. Results: 48 pts (96%) completed CRT, worst toxicity, diarrhoea Grade 3, 6%. Mean number of MRI scans per pt post CRT 1.48, with response seen in 46 pts (92%), of whom 43 (86%) underwent resection, 27 (63%) of which were performed laparoscopically. Median time to surgery was 11 weeks (range 8 to 15 wks). 37pts (86% of those undergoing surgery) achieved R0 resection, mean CRM 6.1mm, mean no. of identifiable lymph nodes 6.4, most frequent pathology ypT3 pN0 26%, pCR 16%, Tmic, 21%. Surgical morbidities included small bowel adhesions requiring laparotomy 8%, infection/abscess 14%. Post-operative mortality 5%. 1 PRRC pt developed liver metastases prior to surgery. Conclusions: CRT with UFT/LV is well tolerated and effective in achieving substantial tumour regression pre-operatively for PRRC. The optimal timing of surgery post CRT at maximal response can be documented with serial MRI, resulting in a high rate of R0 resections. Laparoscopic TME is feasible in this group of pts. [Table: see text]
Efficacy of bevacizumab in combination with irinotecan or oxaliplatin as second-line, third-line or later treatment in metastatic colorectal cancer (MCRC) patients
Authors: Lièvre A. , Samalin E. , Senesse P. , Boyer-Gestin C. , Mitry E. , Lepère C. , Bachet J. , Vaillant J. , Ychou M. , Rougier P. 
Published: March 2020

14558 Introduction: Bevacizumab (Bev) is efficient in MCRC patients (pts) as first-line treatment (L1) with 5FU±irinotecan, and with FOLFOX as second-line (L2). It has no efficacy in 3rd or later-line, alone or with 5FU. In Europe, Bev was approved by the EMEA (European Medicines Evaluation Agency) in 2005 and many patients could not received it in L1 before this date. This study evaluated the efficacy of Bev combined to polychemotherapy (CT) in L2, L3 or later-line in CT refractory pts. Methods: Between May 2005 and October 2006, 38 pts (median age: 54.5 years, range:25–82) received Bev combined with CT as L2 (n=18), L3 (n=6), L4 (n=7), L5 or later-line (n=7). Tumor response (OR) was assessed according to RECIST criteria by CT-scan. Results: Tumor sites: 28 colon and 10 rectum. Number of metastatic sites were 1, 2 and more in 16, 13 and 9 cases, mostly hepatic (89%) or pulmonary (42%). Bev (5mg/kg/2weeks) was combined with FOLFIRI (n=24) or FOLFOX (n=14); 299 cycles were administered, mean: 7.9 cycles/pt (range:2–14). OR rate was 42,1%, stabilization 42,1% and was not different according to the line or the CT regimen (table). Initial progressions were rare. Tolerance was acceptable (no perforation and no severe Hypertension). Conclusion: This study reports a significant activity of Bev at the dose of 5mg/kg combined with FOLFOX and/or FOLFIRI in CT refractory pts. These results warrant prospective studies of Bev combined with active CT in CT refractory pts who could not received Bev in the setting of the EMEA authorization. [Table: see text] No significant financial relationships to disclose.
Altered circadian rhythm in rest and activity (CircAct): Independent prognostic value for survival in patients (pts) with metastatic colorectal cancer (MCC)
Authors: Innominato P. F. , Bjarnason G. A. , Garufi C. , Focan C. , Moreau T. , Gorlia T. , Waterhouse J. , Giacchetti S. , Lévi F. A. 
Published: March 2020

14573 Background: Altered CircAct accelerated tumor growth in experimental models (JNCI 2002, 2005; Cancer Res 2004). CircAct was found to be related to survival in two studies (St) in MCC pts (St 1, Clin Cancer Res 2000; St 2, ASCO 2005 #3553). The current study attempted to provide an independent prognostic stratification criteria for survival according to baseline CircAct as a first step toward the development of a comprehensive prognostic model based on circadian physiology. Methods: CircAct was continuously and non- invasively assessed over 72h with a wrist accelerometer (Ambulatory Monitoring, USA), before chemotherapy in two independent datasets of 169 MCC pts (60% pretreated) at Paul Brousse Hospital (St 1) and 130 chemo-naïve MCC pts registered in the international EORTC 05963 trial (St 2). Activity distribution during rest and wakefulness was objectively quantified by I<O (50=no rhythm; 100=marked rhythm). Kaplan-Meier survival curves with logrank tests and Cox regression models were used for analyses. Results: In both St, pts with I<O = 92 (21% in St 1 and 22% in St 2) displayed a significantly poorer survival as compared to those pts with I<O > 92 (Table). The hazard ratios (HR) were 0.37 [95%CI: 0.25 to 0.55] (p<0.0001) in St 1 and 0.56 [0.36 to 0.87] (p=0.01) in St 2. The prognostic value of altered CircAct persisted after adjusting for PS (HR=0.46 [0.30 to 0.69], p=0.0002 in St 1; HR=0.61 [0.38 to 0.97], p=0.04 in St 2). Conclusions: The independent stratification of MCC pts for survival according to baseline altered CircAct occurred using a threshold value of 92 for I<O in both separate datasets. Subsequent studies will involve additional biomarkers of circadian physiology (cortisol, melatonin, clock genes) in order to further improve this prognostic stratification as a step toward tailored treatment of MCC pts. [Table: see text] No significant financial relationships to disclose.
Pulmonary and hepatic metastasectomy in colorectal cancer–is it worth it
Authors: Demir G. , Gürsu R. U. , Pekmezci S. , Kaynak K. 
Published: March 2020

14574 Forty eight patients (24 males and 24 females) with colorectal carcinoma and lung or hepatic metastasis who had undergone metastasectomy were evaluated retrospectively. The mean age was 58.12±8.34 years (43–79 years). The mean age of the males was 60.16±8.21 years (47–79 years), while it was 56.08±8.13 years in the females (43–71 years). Among the 48 metastasectomies that were performed, 11 were pulmonary metastases, and 37 were hepatic metastases. The mean time to the hepatic metastasectomy after primary surgery was 324.37±420.04. Among the hepatic metastases, one was located in the caudate lobe, 16 were located in the right lobe, and 20 were located in the left lobe. Thirty of the patients had received postoperative chemotherapy after liver metastasectomy. Twenty two of the patients who underwent liver metastasectomy (59%) had a recurrence. In 14 of these, (38%) the recurrence was in the liver. Overall survival of the patients with liver metastasectomy was 914.19±577.08 days. Survival after metastasectomy was 578.80±331.54 days. On the other hand, the mean time to pulmonary metastasectomy after primary surgery was 811.81±552.06 days. Eight of the lung metastases were located in the right lobe, whereas 3 were located in the left lobe. Three patients had concomittant metastases in the right upper and lower lobes, and one patient had additional liver metastasis. Eight of the patients who underwent pulmonary metastasectomy had received postoperative chemotherapy. Five of the patients who underwent pulmonary metastasectomy (45%) had a recurrence. Two of the patients had recurrence in the lung, while 3 had recurrence elsewhere. Overall survival of the patients who underwent pulmonary metastasectomy after initial surgery was 1341.54±816.21 days. Survival after metastasectomy was 528.81±365.45 days while recurrence-free survival after pulmonary metastasctomy was 342.18±125.71 days. Conclusion: This study suggests that patients with pulmonary metastasectomies have even beter clinical outcomes then hepatic metastasectomies in patients with metastatic coloercatla cencer. Every effort should be made to perform both pulmonary and hepatic metastasectomies in this group of patients. No significant financial relationships to disclose.
Addition of bevacizumab (beva) to xeliri/xelox chemoradiotherapy in neoadjuvant setting for patients (pts) with locally advanced rectal cancer (LARC): A feasibility study
Authors: Privitera G. , Spatola C. , Acquaviva G. , Di Franco G. , Salvo R. , Raffaele L. , Salamone V. , Ettorre G. 
Published: March 2020

14583 Background: Preoperative chemo-radiotherapy in pts with LARC has been extensively evaluated, although no standard treatment has been defined. We planned to add the new anti-VEGF monoclonal antibody bevacizumab in the neoadjuvant setting, in order to evaluate whether the modifications induced in normal and tumor microcirculation and vascularity could increase the treatment toxicity profile and induce relevant complications during the surgery. Methods: From Jul 05 to Sept 06, pts with histologically proven uT3–4 N± or uT2 N+ rectal cancer were treated with capecitabine 1,000 mg/m2 bid on days 1–14 before chemoradiation phase and then 825 mg/m2 bid on days 22–55 plus irinotecan 180 mg/m2 (XELIRI) or oxaliplatin 130 mg/m2 (XELOX) on days 1, 22, 43 in combination with BEVA 5 mg/kg q2w starting on day 1 until the completion of the treatment. Radiotherapy was administered according to our previous study (45 Gy to the whole pelvis, plus 9 Gy as conc. boost to the CTV during the last six fractions). Surgery was carried out 8 weeks after the completion of chemoradiation. Results: Eleven pts (7 male/4 female), ECOG PS 0–1, were enrolled in this study. No patient showed systemic disease at the time of diagnosis. Six pts received XELIRI chemotherapy, 5 pts XELOX. Ten pts completed the planned chemotherapy schedule, one patient discontinued chemotherapy administration after the second irinotecan infusion due to GI grade III toxicity. All eleven pts completed the planned radiation treatment, with a total dose of 54 Gy. Three pts reported moderate hypertension, treated with standard anti-hypertensive drugs, and one had epistaxis, but no one required discontinuation of BEVA Conclusions: The use of BEVA in the neoadjuvant setting of pts with LARC is feasible and safe. In combination with XELIRI/XELOX chemoradiation, BEVA does not increase the treatment toxicity profile, nor provoke any surgical delay or modifications. BEVA in this setting should be further evaluated in larger phase II studies, in order to estimate the rates of clinical and pathologic complete and partial response, compared to XELIRI/XELOX chemoradiation schedules. No significant financial relationships to disclose.
Outcome of metastatic colorectal cancer patients receiving second line chemotherapy in Marmara University Hospital
Authors: Dane F. , Gumus M. , Ozturk A. , Yumuk F. , Iyikesici S. , Basaran G. , Cabuk D. , Teomete M. , Turhal N. S. 
Published: March 2020

14588 Background: With the development of oxaliplatin and irinotecan, multiple effective regimens are now available in advanced colorectal cancer (CRC), both as first- and second-line treatment options. Exposure to all of the active drugs is effective in prolonging overall survival (OS) and time to progression (TTP). There are limited studies, if any, analyzing the outcome of second line chemotherapy in metastatic CRC in Turkey. Thus, we aimed to evaluate the outcome of second-line treatments in metastatic CRC patients. Methods: Among 173 patients with metastatic CRC who were given first line chemotherapy 106 (47 female, 59 male) were administered second line treatment after progression. All patients histologically confirmed colorectal adenocarcinoma with ECOG performance score of 2 or lower, and received second line therapy for metastatic CRC after experienced disease progression during or following treatment with first-line therapy were entered the study. The patients were evaluated clinically and radiologically after each three-cycle period, and chemotherapy was changed or stopped if the cancer has progressed. Age, gender, grade, chemotherapy type (combination vs single agent), lymphatic, vascular, and perineural invasion, were analyzed as prognostic factors. Results: At a median follow up of 10 (range 1–40) months from the start of second line chemotherapy median TTP and OS time were 5 and 16 months respectively. Median age was 62 years (range 27–89). After second line therapy 16% of the patient had objective response rate (0.9% complete responses plus 15.1% partial responses), 37.7% had stable disease resulting in a tumor control rate of 53.7%, and 46.2% had progressive disease. One-year progression free survival and OS rates were 15 % and 53.5%, respectively. No difference was seen in the survival of patients received combination or single agent second line chemotherapy (p=0.14). Overall, over 12% of the patients suffered from grade 3 or 4 adverse effects. In multivariate analysis histological grade (p=0.015) was the only independent prognostic factor for survival. Conclusion: The survival outcome and adverse effects of second line treatments in Turkish patients in our department with metastatic CRC is consistent with the worlds’ literature. No significant financial relationships to disclose.
Weekly low dose irinotecan and daily oral anticancer drug chemotherapy for metastatic colorectal cancer (MCRC) patients more than 75 years old
Authors: Sasaki K. , Takasaka H. , Sawada T. , Ezoe E. , Araya J. , Takada Y. , Furuhata T. , Hirata K. 
Published: March 2020

14594 Background: The percentage of CRC patients more than 75 years old is expected to rise in Japan, too. However we have little data on the efficacy and toxicity of chemotherapy in elderly MCRC patients. The aim of this study was to evaluate the objective tumor response rates and toxicities in elderly MCRC patients treated weekly low dose irinotecan and daily oral anticancer drug (UFT or S-1) chemotherapy. Methods: Patients with MCRC were treated on an out-patient treatment basis with irinotecan 60mg/m(2) as an intravenous 90 minutes infusion on weekly plus UFT 300 mg/m(2) or S-1 60 mg/m(2) in 2 divided doses given orally on day 1 to 5 in every week. All the lesions were evaluated with CT and/or MRI scan. Results: From 2001 to 2005, we treated 20 elderly MCRC patients. There were 13 men and 7 women. Fourteen patients were 75∼79 years old and 6 patients were 80 years or more. Chemotherapy was given more than 3 months (3∼30M). To date, 495 cycles (median 24, range 7–98) have been administered. There were 8 PR, 10 SD and 2 PD. The overall response rate was 40% and disease control rate (PR + SD) was seen 90% of pts. Progression free survival time of this regimen is 9.3 months. Median survival time was 16.0 months. One and 2 years survival rates were 72% and 13%. No toxic death was reported. There was no grade III/IV toxicity and all adverse events were manageable. All patients were treated on an out-patient clinic. Conclusions: These results confirmed that this chemotherapy combination is active with acceptable tolerability and QOL maintenance in elderly patients with MCRC. Chemotherapy in elderly patients with MCRC should not be influenced by the chronologic age of the patient. No significant financial relationships to disclose.
Mitomycin-C and capecitabine as salvage chemotherapy in pre-treated patients with advanced colorectal cancer
Authors: Gennatas C. G. , Michalaki V. , Gennatas S. , Kouvaris J. , Smyrniotis V. , Vasiliou J. 
Published: March 2020

14595 Background: To assess the activity and tolerability of the combination of Mitomycin C and Capecitabine in patients with metastatic colorectal cancer after failure of irinotecan, 5-fluorouracil (5-FU), folinic acid and oxaliplatin-containing regimens. Methods: We retrospectively reviewed 31 patients with pre-treated advanced colorectal cancer. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1000 mg/m2 twice daily on days 1–14, was initiated. Cycles were repeated every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. Results: Main patient characteristics were median age 63 years (range, 45–73); male/female ratio, 19/12. One hundred forty- six courses of therapy were given (median number, 3; range, 2–9). All patients were assessable for response, and all were assessable for toxicity. Fourteen patients had stable disease (45%). Median time to progression was 3 months (range, 1–10) and median overall survival was 8 months (range, 3–28). The regimen was very well tolerated without significant toxicity. Grade 2 toxicities were palmar-plantar erythema 6%, hematological 35%. Conclusions: Our findings suggest that the combination of Mitomycin C and Capecitabine in pre-treated patients with advanced colorectal cancer is safe and effective with an acceptable toxicity profile and a convenient administration schedule. However, further evaluation of other salvage regimens seems to be warranted. No significant financial relationships to disclose.
Concurrent chemoradiotherapy with S-1 and cisplatin for locally advanced esophageal cancer
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Okeya M. , Kobayashi K. , Watanabe H. , Hibino Y. , Ryuge N. , Goto H. 
Published: March 2020

15007 Background: Both oral fluoropyrimidine anti-cancer agent (UFT, S-1) and cisplatin can enhance the effectiveness of radiotherapy. We previously reported a phase II trial of UFT and cisplatin combined with radiotherapy (Int J Clin Oncol 8 (2003): 305–311) and a phase I trial of S-1 and cisplatin combined with radiotherapy (Jpn J Cancer Chemother 33 (2006): 224–229) for advanced esophageal cancer. The present study analyzes the efficacy of concurrent chemoradiotherapy by using S-1 and cisplatin for locally advanced esophageal cancer. Methods: Chemoradiotherapy consisted of two courses. The first course included 30 Gy of radiotherapy given over 3 weeks, together with daily oral administration of S-1 (80 mg/m2/day) for 2 weeks and a 24-h infusion of cisplatin (70 mg/m2) on day 8. The second course of chemoradiotherapy was administered after 2 weeks. For patients who exhibited an objective response to chemoradiotherapy, at least 2 four-week courses consisting of chemotherapy of S-1 and cisplatinon were administered. If a patient was unable to take S-1 as a capsule, S-1 was administered in the powdered form with water. Results: Fifty-nine patients were enrolled. They had the following characteristics: median age 65 years; M/F 52/7; PS 0/1/2: 33/19/7. There were 9 patients with stage II tumors and 50 with stage III. Fifty-four patients (92%) completed 2 courses of chemoradiotherapy. The major toxicity was myelosuppression. Fifteen patients (25%) developed grade 3 leukocytopenia, while 7 patients (12%) developed grade 4 leukocytopenia. Nonhematologic toxicity was moderate: grade 2 nausea/vomiting, pain, oral mucositis, and renal dysfunction occurred in 20%, 12%, 5% and 5% of patients, respectively. In stage II cases, complete response (CR), partial response (PR), and response rates were 78%, 22%, and 100%, respectively. In stage III cases, CR, PR, and response rates were 58%, 32%, and 90%, respectively. All stage II patients survived. In stage III cases, the 1-year survival rate was 70% and the 3-year survival rate was 44%. Conclusions: Chemoradiotherapy with S-1 and cisplatin is convenient, tolerable, and effective, and may be a promising nonsurgical management option for patients with locally advanced esophageal cancer. No significant financial relationships to disclose.