bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tegafur combined with oxaliplatin and 5-FU versus FOLFOX4 for advanced colorectal cancer: a randomized controlled study
Authors: Lingxiang L. , Yongqian S. , Ping L. , Puwen H. , Yongmei Y. 
Published: March 2020

13566 Background: To determine the activity and side-effect of tegarfur injection combined with L-OHP and 5-FU, comparing with FOLFOX4 as the therapy for advanced colorectal cancer. Methods: 60 patients, proved pathologically, were divided into 2 groups at random. Group A received the intravenous administration of tegafur(800mg/m2 IV 3hrs qd d1–5),leucovorin(100mg/m2 IV 2hrs qd d1–5) and L-OHP(130mg/m2 IV 2hrs d1) every 21 days. FOLFOX4 was applied in the group B. The endpoint included response rate (RR), progression free survival (PFS), overall survival(OS) and quality of life(QOL). Results: The response rate was 39.3% in the group A, while median time to progression was 9.5 months with median survival time of 11.6 months. In the group B, the response rate was 48.1% and median time to progression was 9.4 months with median survival time of 12.1 months. No significant differences were found between treatment arms in curative effect, survival time and side effect(P>0.05). With respect to QOL, the group A achieved higher PS than B during treatment (P<0.001). Conclusions: The intravenous administration of tegafur, leucovorin and L-OHP is a well-tolerated, effective, and feasible schedule for advanced colorectal cancer that yields comparable efficacy and side effect compared with FOLFOX4. Meanwhile, the former achieves the better QOL. No significant financial relationships to disclose.
Capecitabine plus irinotecan (CAPIRI) as first-line treatment for patients (pts) with metastatic colorectal cancer (MCRC)
Authors: Laudani A. , Agostara B. , Savio G. , Leonardi V. , Salvagno L. , Palmisano V. , Usset A. 
Published: March 2020

13573 Background: Twice-daily oral capecitabine mimics 5-FU infusion and has superior efficacy, improved safety and convenience compared with 5-FU/LV in MCRC and early-stage colon cancer. Preclinical and phase I/II clinical data suggest supra-additive efficacy of X + irinotecan and no significant pharmacokinetic interactions. We evaluated the efficacy and safety of X plus weekly irinotecan (CAPIRI) in 3-week cycles as first-line treatment for MCRC. Methods: Pts with no prior treatment for MCRC received irinotecan 80 mg/m2 i.v. infusion on d1&8 + capecitabine 1000 mg/m2 orally bid d1–14, q3w. Results: Baseline characteristics of the 39 enrolled pts (22 men/17 women) were: median age 59.9 years (range 38–76), ECOG PS 0–1, colon cancer (n=25), rectal cancer (n=14), metastatic sites (liver 74%, pelvis 20%, nodes 23%, lung 18%, peritoneum 10%, primary tumor 20%). Previous treatments were as follows: adjuvant chemotherapy (36%), radiotherapy (5%), neoadjuvant chemotherapy (3%). Pts received a total of 199 cycles (mean 5.1 per pt, range 1–13). All 39 pts were evaluable for safety and 38 for efficacy. The most common treatment-related grade 3/4 adverse events were nausea/vomiting (23% of pts), diarrhea (10%), and leucopenia (5%). The overall response rate was 45%, including 3 complete and 14 partial responses. A further 8 pts (21%) had stable disease. The duration of response in pts with a complete response was >10 months. Conclusions: These early findings indicate that this combination is effective and well tolerated as first-line treatment for MCRC. Replacing 5-FU with capecitabine in XELIRI offers benefits to the pt in terms of efficacy, safety, convenience, reduced discomfort and avoidance of central venous access compared with infusional 5-FU/LV-based regimens (IFL and FOLFIRI). No significant financial relationships to disclose.
Adjuvant CCRT for locally advanced rectal cancer: Uracil-tegafur? Or intravenous fluorouracil?
Authors: Hsieh C. H. , Chen Y. J. , Chang K. H. , Hsu H. H. , Liu C. K. , Hung S. K. , Chen H. W. , Lai Y. L. , Hsu T. C. 
Published: March 2020

13582 Background: This prospective, nonrandomized study was conducted to compare the efficacy and toxicity of postoperative concurrent chemoradiation therapy (CCRT) using daily oral uracil-tegafur plus leucovorin (UFUR/LV) vs. weekly intravenous fluorouracil plus leucovorin (5-FU/LV) in patients with locally advanced rectal cancer. Methods: From November 1996 through December 2004, 30 patients with stage II or III rectal cancer were enrolled. Seventeen received oral UFUR/LV regiment and thirteen with intravenous 5-FU/LV regiment during CCRT. A weekly infusion of 400 to 450 mg/m2 of 5-FU plus a bolus injection of 80 to 100 mg/m2 of LV and 250 to 300 mg/m2/d of oral UFUR plus 30 to 45 mg /m2/d of oral LV were given separately during RT and for an additional 42 weeks thereafter. Forty-five Gy of whole-pelvis irradiation was followed by a local boost of 5.4 to 14.4 Gy to the tumor bed delivered in 33 fractions. Analytical method was Kaplan-Meier method. Results: Mean survival in the UFUR/LV group was 36 months compare with 30 months in the 5-FU/LV group. The 2-year OS, DFS and LCR were 68.1% vs. 65.8%, 54.9% vs. 50.4%, and 79.4% vs. 83.9%, (p > 0.05), respectively. There were no treatment-related deaths and grade 4 toxicity in both groups. Grade 3 of dermatitis, gastrointestinal, and hematologic toxicity was noted in the 5-FU/LV group. Conclusions: Postoperative CCRT with oral UFUR/LV in locally advanced rectal cancer provides an alternative way for those who have difficulty with an intravenous regimen due to it was more tolerable and less toxicity and has similar survival rate. No significant financial relationships to disclose.
Upregulation of thymidine phosphorylase (TP) by radiation (XRT): Phase II study of capecitabine (CAP) with XRT in pts with locally advanced (LA) pancreatic cancer
Authors: Roy S. , Russo S. , Black G. , Eloubeidi M. A. , Steg A. , Zelterman D. , Johnson M. R. , Diasio R. B. , Saif M. W. 
Published: March 2020

14001 Background: Preliminary studies have shown that XRT unregulates TP, the main enzyme responsible for activity of CAP. The objectives of this phase II study were to further evaluate effect of XRT on TP, DPD, and TNF-alpha as well as response and efficacy of CAP with concurrent XRT in pts with LA pancreatic cancer. Methods: Pts received 50.4 Gy XRT with CAP at 1600 mg/m2 M-F × 6 wks determined from our phase I study (JCO, Dec 2005). Following CAP-XRT, stable and responding pts on CT scan were treated with CAP 2000mg/m2 × 14 days q 3 wks till progression. Restaging was performed every 9 wks. Tumor specimens were procured with EUS-FNA 1 wk prior and 2 wks after CAP-XRT to evaluate TP, DPD, and TNF-alpha mRNA levels by RT-PCR. A sample size of 20 was selected (mean 1 vs. S with mean 0=13.5; alpha = 0.05; power = .99; t-test). Results: 19 pts (median age: 67; M/F: 7/12) were enrolled at UAB between March 2004 and June 2005. 4 pts (21%) had confirmed partial responses and 13 (68%) had stable disease. 2 pts underwent surgery (Ro in 1; extensive fibrosis in 1). Six-month survival rate was 89%. We have not met enough deaths to estimate median survival. Grade 3 and 4 toxicities included: nausea/vomiting (5%), thrombosis (5%), hyperbilirubinemia (5%), and grade 3 GI bleeding (5%). No hematological toxicities except grade 1 thrombocytopenia (5%) and grade 1 anemia (10%). All pts completed full CAP-XRT with 3 dose reductions (by 20%). Pts received mean of 5.4 cycles (range: 3–15) of CAP alone with a total of 104 cycles with dose reductions in 7 cycles (by 25%). TP was elevated during wk 2 when compared to pre-XRT TP (P = .005) but DPD was not (P = .13) nor was TNF-alpha (P = .37). No correlation between TP and TNF-alpha was noticed. No association between TP/DPD ratio and efficacy of CAP was identified. Tumor TP expression was higher (183.16) in pt with GI bleeding. Conclusions: This Phase II study further confirms our Phase I results that CAP-XRT is an effective, tolerable, and an easy alternative to infusional 5-FU regimen for pts with LA pancreatic cancer. Also TP upregulation by XRT was statistically significant. While these results support use of CAP-XRT in pancreatic cancer, there appears to be additional genes (other than TP, DPD) associated with response to CAP and CAP-XRT. [Table: see text]
A multicenter phase II study of pemetrexed and cisplatin in patients with advanced gastric cancer (AGC)
Authors: Bang Y. , Kim Y. , Chung H. C. , Kang W. , Park S. , Yang S. , Park H. , Kim C. , Park B. , Otero J. C. 
Published: March 2020

14008 Background: Pemetrexed is a novel folate antimetabolite, and it inhibits a number of folate-dependent enzymes. This agent has demonstrated activity in a variety of tumor types including AGC. This study was performed to evaluate the combination of pemetrexed and cisplatin in the treatment of AGC. The primary endpoint was response rate, and secondary endpoints were duration of response, time to progressive disease, time to treatment failure, overall survival, and toxicity. Methods: Patients with stage IV AGC not to be amendable to curative surgery and measurable disease were eligible. Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 were given on day 1, every 21 days. Treatment was supplemented with folic acid, vitamin B12, and dexamethasone. Response was assessed by RECIST, and toxicity was assessed by NCI-CTC v 2.0. Results: From October 2003 to September 2004, 51 patients were enrolled, but 1 did not meet the eligibility criteria. There were 37 men and 13 women with a median age of 56 years (range, 24–69) and an ECOG PS 0/1 for 14/36 patients; all had metastatic disease. Of 50 evaluable patients, there were no complete responses, and 13 had confirmed partial responses (26%; 95% CI, 14.6%-40.3%). Fifteen patients (30%) had stable disease, and 21 (42%) progressed, and 1 (2%) was unknown. Among 13 responders, the median durarion of response was 3.60 months (95% CI, 2.80–9.40). Median time to progressive disease was 2.8 months (95% CI, 2.20–4.40), and median overall survival was 6.6 months (95% CI, 4.80–10.40). The median time to treatment failure was 2.10 months (95% CI, 1.00–2.80). Survival estimates were 32.0% at 3 months and 7.0% at 6 months. A total of 212 cycles were administered to 51 patients (median 4 [range, 1–13]). Based on 51 patients, most common grade 3/4 hematologic toxicities were neutropenia (49.0%), leukopenia (19.7%), and anemia (13.7%); the most common grade 3/4 nonhematologic toxicities were hyponatremia (15.7%), anorexia (9.8%), nausea (7.8%), and vomiting (7.8%). Conclusions: : The combination of pemetrexed and cisplatin in the current dose and schedule has a modest activity and a mild toxicity profile in patients with AGC. Further study is warranted using a different dose and treatment schedule. [Table: see text]
Hepatic arterial infusion (HAI) of oxaliplatin in advanced hepatocellular cancer (HCC): A phase I study
Authors: Rathore R. , Iannitti D. , Soares G. , Wanebo H. , Maia-Aucna C. , Safran H. 
Published: March 2020

14010 Background: We performed this phase I study is to evaluate the feasibility and determine the Maximally Tolerated Dose of HAI-oxaliplatin given every 3 weeks in advanced HCC. Methods: Patients (pts) with unresectable or recurrent HCC were eligible for therapy on this protocol. HAI-oxaliplatin was administered over 2 hours via a percutaneously placed hepatic arterial catheter or a surgically inserted hepatic arterial infusion pump. Therapy was continued until disease progression or excessive toxicity not amenable to appropriate modifications. Restaging was performed after every 2 cycles. Dose escalation levels for HAI-oxaliplatin are 90 mg/m2, 110 mg/m2, 130 mg/m2 and 150 mg/m2 given every 3 weeks. Results: A total of 16 patients have been enrolled and toxicity data are available for all patients. Median age was 61 yrs (range 47–84 yrs), there were 15 men and 1 woman. The stage distribution is: stage II-3 pts, stage III- 7 pts, stage IV- 6 pts. Prior therapies including chemoembolization (CE) in 3 pts, radiofrequency ablation (RFA) in 3 pts, and both RFA and CE in 1 pt. A total of 37 cycles (range 1–3) have been delivered. Levels 1 and 3 had to be expanded to 6 pts each due to major toxicity in 2 pts at each level. Level 2 was expanded as 1 pt was non-compliant. Major toxicities are shown below. One patient developed embolic bowel ischemia after his HAI procedure. There was one episode each of duodenal perforation and duodenal ulceration. Traditional grade 3/4 hematologic and gastrointestinal toxicities were infrequent. Among 13 pts receiving at least 2 cycles, 3 pts had partial responses (PR) and 4 pts had stable disease (SD). Greater than 50% reduction in AFP was seen in the 3 pts with PR and 2 pts with SD. Conclusions: HAI-oxaliplatin is feasible, well tolerable, and demonstrates activity in this population of pts with advanced HCC. [Table: see text] No significant financial relationships to disclose.
Phase II study of conventional fractionated radiotherapy versus hyper-fractionated accelerated radiotherapy concomitant with low dose gemcitabine for patients with pancreatic cancer
Authors: Maemura K. , Takao S. , Shinchi H. , Noma H. , Hiraki Y. , Nakajo M. , Aikou T. 
Published: March 2020

14017 Background: Concurrent radiotherapy and chemotherapy with gemcitabine (GEM) has been reported to improve the median survival of patients with unresectable pancreatic cancer. Although hyperfractionated accelerated radiotherapy (HART) was administered to pancreatic cancer recently, the efficacy is unclear. Phase II study was conducted to evaluate the efficacy and the toxicity of HART concomitant with twice-weekly low dose GEM compared with conventionally fractionated radiotherapy (CRT) for unresectable pancreatic cancer. Methods: Between April 2001 and April 2004, 34 untreated eligible patients with histologically proven unresectable pancreatic cancer were enrolled. In CRT group (n=15), 50.4Gy was delivered in 28 fractions of 1.8Gy/day. In HART group (n=19), 50Gy was delivered in 40 fractions of 1.25Gy twice a day. All patients were treated with conformal radiation using 5mm multileaf collimeter. Concurrent chemotherapy with GEM (40mg/m2) was administered twice a week to both groups. Chemotherapy was suspended for Grade 3 toxicities or increase in temperature more than 38 °C. Response evaluations were conducted at six weeks after the treatment. Maintenance chemotherapy composed of GEM (1000mg/m2/week) for 3weeks was repeated every 4 weeks thereafter. Results: The median survival time (MST) was 11.3 months in CRT group and 12.9 months in HART group. The 1- and 2-year survival rates were 42.9% and 28.6% in CRT group, 52.9% and 17.6% in HART group. There was no significant difference in response rate between CRT and HART group (35.7% vs. HART; 35.3%). The median time to progression (TTP) was significantly prolonged in HART group (9.7months) compared with CRT group (5.9 months) (p=0.02). Overall treatment time was significantly shorter in HART group (37days) than CRT group (45days) (p=0.002). There was no significant deference in toxicity between CRT and HART group. Conclusions: HART concomitant with low dose GEM was well tolerated with acceptable toxicity and prolonged median TTP and MST with shortening of treatment time compared with conventional radio-chemotherapy. This regimen appears to be one of the crucial therapies for patients with unresectable pancreatic cancer. No significant financial relationships to disclose.
Glufosfamide (GLU) plus gemcitabine (GEM) in advanced solid tumors: Phase 1 results
Authors: Chiorean E. G. , Dragovich T. , Hamm J. T. , Langmuir V. K. , Kroll S. , Jung D. T. , Colowick A. B. , Loehrer P. J. 
Published: March 2020

14022 Background: Glufosfamide is glucose linked to isophosphoramide mustard, the active metabolite of ifosfamide. Cancer cells use glucose at a higher rate than normal cells, which may lead to preferential metabolic targeting by GLU. GLU has shown activity in patients (pts) with pancreatic cancer in Phase 1/2 studies with the dose-limiting toxicities (DLT) being nephrotoxicity and neutropenia. The MTD was 4500 mg/m2. In preclinical studies, GLU has shown additive activity when combined with GEM. The objectives of this study are to establish the maximum tolerated dose (MTD) and to evaluate the safety, efficacy and PK of GLU + GEM in advanced solid tumors. Methods: Eligible pts had Karnofsky Performance Status ≥70, no prior GEM, at least one lesion by RECIST, creatinine clearance (CrCL) ≥60 mL/min and acceptable hematologic and liver function. Cohorts of 3–6 patients were treated with GLU 1500–4500 mg/m2 IV over 4 hours on Day 1 and GEM 1000 mg/m2 IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle for up to 6 cycles. CT scans were obtained every 8 weeks. Detailed PK sampling was performed. Results: Nineteen pts with pancreatic (8), gall bladder (4) and other (7) cancers were enrolled. Two DLTs have occurred: Grade 3 fatigue at 2500 mg/m2 and Grade 4 thrombocytopenia at 4500 mg/m2. Both cohorts were expanded. No DLTs occurred in the 1500 or 3500 mg/m2 cohorts. Three pts completed all 6 cycles and 3 pts continue on study. Reasons for early discontinuation were progressive disease (10), clinical deterioration (1), AE (1) and death (1). Grade 3/4 neutropenia occurred in 7 pts (5 during Cycle 1) and Grade 3/4 thrombocytopenia in 5 pts (2 during Cycle 1). The CrCL fell below 60 mL/min in one patient. No objective tumor responses have been reported; 10 of 18 (56%) evaluable pts had stable disease (SD) at 8 weeks, including 1 pt with heavily pretreated ovarian cancer with ongoing SD after 8 months on therapy. PK analyses suggest no interaction between GLU and GEM. Conclusions: Phase 1 data indicate that full dose GLU (4500 mg/m2) can be given safely in combination with GEM. Both early and delayed Grade 3/4 thrombocytopenia and neutropenia have been observed. A Phase 2 cohort of 28 pts with pancreatic adenocarcinoma is currently enrolling. Studies with GEM/GLU in other tumor types are planned. [Table: see text]
Chemotherapy in advanced biliary tract carcinoma (BTC): A comprehensive analysis
Authors: Eckel F. , Schmid R. M. 
Published: March 2020

14036 Background: BTC are uncommon but highly fatal malignancies in the United States and Europe. Unfortunately, most BTC are diagnosed at advanced stages when the tumor is unresectable. Due to the lack of phase III studies there is no standard regimen for palliative chemotherapy of BTC. The aim of this study was to analyze existing data of published clinical trials, even small and non-randomized, and identify superior regimens, which may represent a quasi standard of care of palliative chemotherapy in this disease. Methods: Data for this analysis were identified by searches of PubMed and references from relevant articles using the search terms “biliary tract neoplasms”, “bile duct neoplasms”, “cholangiocarcinoma”, and “gallbladder neoplasms”. Only papers published in English since 1985 were included. Additionally abstracts from ASCO meetings presented since 1999 were included. Results: 88 trials were analyzed. The overall response rates (OR) of this trials were in the range of 0–83%. There were 497 responders out of 2137 patients corresponding to a pooled OR of 23.3% (95%CI 21.5–25.2%). The median progression free survival (PFS) and overall survival (OS) for all patients was 4.1 and 8.0 months, respectively. There was a significant correlation between OR and PFS (r=0.49; p=0.001) and PFS and OS (r=0.76; p=0.000) but not between OR and OS. Gemcitabine (GEM) and platinum analogs (P) had a significant positive impact on OR, whereas the impact of taxanes and irinotecan was negative. OR of subgroups defined by 5-FU, GEM, and P were analyzed in detail. There was only a trend of an increased OR between 5-FU and GEM without P (17 vs 22%). Combination with P increased significantly the OR of 5-FU by 10% (17 vs 27%) and of GEM by 20% (22 vs 42%). Conclusions: The pooled OR of mostly small trials of palliative chemotherapy in BTC is about 23%. With GEM alone no significant improvement could be achieved compared to 5-FU or capecitabine. However, doublets of GEM in combination with P synergistically increased OR. Results of GEM plus P are promising and should be further evaluated by large RCT. In the meantime GEM plus P may represent at least a good option for patients in good general condition. No significant financial relationships to disclose.
Selection of induction chemotherapy (CT) in esophageal and gastroesophageal junction cancer by positron emission tomography (PET)
Authors: Irigoyen A. , Delgado J. , Rodriguez A. , Ferron J. , Luque R. , Reche P. , Gonzalez E. , Conde V. , Rodriguez C. , Pleguezuelos J. 
Published: March 2020

14041 Background: Preoperative CT improves survival in esophageal cancer. 50% of patients (pts) do not respond to cisplatin+5-FU (C+F). The reduction of fluorodeoxyglucose uptake after 14 days (d) of CT predicts clinical response (rsp). Our objective was to measure the rsp (rsp) rate after CT adjusted according to PET rsp. Methods: Eligible pts were ≥ stage II esophageal cancer and able to tolerate CT. By adjusting CT according to PET rsp, we expected an increase of rsp rate by 25%. Taking into account a confidence level of 90%, an error β of 20% and a minimal error of 15% (even with such a high error rate the data will exceed the standard results), we calculated a sample size of 23 pts. All underwent esophagoscopy, computed tomography and PET scan prior to C (100mg/m2 d1) +5-FU (1,000mg/m2 d1–5). If PET rsp after first cycle (uptake decreased ≥ 35%), we continued up to third C+F cycle, then if endoscopy rsp: C+F + concurrent radiation only if stage II or III. If no endoscopy rsp, surgery only if stage II or III. On the other hand, if the pts had no rsp in PET after first C+F cycle they continued with 2 cycles of docetaxel (35mg/m2 d 1 & 8) and irinotecan (50mg/m2 d 1 & 8) (D+I) every 21 d and then if endoscopy rsp: radiation + docetaxel only if stage II or III. If no endoscopy rsp, surgery. Results: Since 2/04, 23 pts have been enrolled. Location: 2 cervical, 4 upper thoracic, 7 mid-thoracic, 10 GE junction. PET stage: 7 IIA, 6 IIB, 2 III, 2 IVA, 6 IVB. Up-staging with PET in 6 pts, down-staging in 4 pts. Histology: 10 Adenocarcinoma, 13 squamous carcinoma. Improved swallowing function: from a total of 12 PET responders, 9 had a clinical rsp after C+F, 3 did not. From 11 PET non-responders, 7 had a clinical rsp after D+I, 4 did not. Global clinical rsp = 16/23 (70%). Endoscopy rsp (frequent inaccuracy by overstaging): from a total of 12 PET responders, 6 had a clinical rsp after C+F, 6 did not. From 11 PET non-responders, 7 had a clinical rsp after D+I, 4 did not. Global clinical rsp = 13/23 (57%). Conclusion: Our results suggest that it is possible to significantly increase the percentage of pts who respond to induction CT adjusted according to PET in esophagogastric cancer before concurrent chemoradiotherapy or esophagectomy, or both. No significant financial relationships to disclose.