bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final safety findings from a randomized phase III trial of capecitabine + oxaliplatin (XELOX) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with stage III colon cancer
Authors: Schmoll H. J. , Tabernero J. , Nowacki M. , Maroun J. , Price T. , Lim R. , Van Cutsem E. , De Braud F. , Haller D. 
Published: March 2020

3569 Background: Adjuvant capecitabine results in at least equivalent disease-free survival (DFS) to i.v. bolus 5-FU/LV in stage III colon cancer [Twelves et al. 2005]. Early phase III data in 1st-line metastatic colorectal cancer suggest that XELOX is as safe as oxaliplatin + infusional 5-FU ± LV [Sastre et al. 2005; Ducreux et al. 2005]. The XELOXA study compared safety and efficacy of XELOX vs. bolus 5-FU/LV (the standard regimen at study start) as adjuvant therapy for stage III colon cancer. Methods: Pts with resected disease were randomized to receive either XELOX (capecitabine 1000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1, q3w for 8 cycles) or i.v. bolus 5-FU/LV (Mayo Clinic, LV 20 mg/m2 + 5-FU 425 mg/m2 d1–5, q4w for 6 cycles; or Roswell Park [RP], LV 500 mg/m2 + 5-FU 500 mg/m2 d1, w1–6 in 8w cycles x4). Centers’ preferred 5-FU/LV regimen was selected at study start and used in all pts. Results: 1861/1886 pts randomized between Apr 03 and Oct 04 are evaluable for safety. The rate of related grade 3/4 adverse events (AEs) was 54% for XELOX and 45% for 5-FU/LV ( table ). 60-day all cause mortality was 1.0% in both arms. Treatment-related death rate within 28 days from last dose was 0.7% for XELOX and 0.5% for 5-FU/LV. Conclusions: XELOX causes less myelosuppression and stomatitis but more skin toxicity than 5-FU/LV. The inclusion of oxaliplatin adds neurosensory toxicity. Cross-study comparison of grade 3/4 AEs in the current and MOSAIC trials suggests that XELOX safety is similar to FOLFOX4, with the advantage of an oral fluoropyrimidine-based regimen. Final safety data will be presented at the meeting, and efficacy data will be available in 2007. [Table: see text] [Table: see text]
A dose attenuated schedule of irinotecan and capecitabine in combination with celecoxib in advanced colorectal cancer
Authors: El-Rayes B. F. , Shields A. F. , Vaishampayan U. , Heilbrun L. K. , Zalupski M. M. , Philip P. A. 
Published: March 2020

3584 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in the majority of colorectal cancers. Inhibition of the COX-2 enzyme can sensitize colorectal cancer cells to the apoptotic effects of chemotherapeutic agents and block angiogenesis. This phase II study was undertaken to determine the effects of adding celecoxib to a dose attenuated irinotecan and capecitabine regimen. Methods: The primary objective was to estimate the objective response rate of patients with metastatic colorectal cancer treated with irinotecan, capecitabine, and celecoxib. Previously untreated patients, except for adjuvant therapy, with metastatic colorectal adenocarcinoma were eligible for this study. Patients received irinotecan 70 mg/m2 (over 30 minutes) on days 1 and 8, and capecitabine 2,000 mg/m2/day from day 1 to 14 of a 21-day cycle. Celecoxib was administered at a dose of 400 mg twice-daily starting on day -7 until termination from study. Results: A total of 51 patients (median age 58 years) have been enrolled on the study. The results presented are for the first 48 patients registered to the study. Median performance status was 1. A median number of 5.5 cycles (range 0- 18) were administered. In an intention to treat analysis, objective response rate was 50%. The median progression free survival was 6.9 months (90%CI; 4.7–8.2). Median survival is ≥19.4 months. No treatment related deaths were observed. The only grade 4 toxicity was diarrhea in 2 (4%) patients. Grade 3 toxicities were diarrhea (33%), hand-foot syndrome (8%), nausea (13%), vomiting (8%) and neutropenia (12%). Conclusion: Lowering the dose intensity of irinotecan in this study did not appear to compromise the treatment outcome and markedly improved the therapeutic index of this combination. Celecoxib can be safely administered in combination with irinotecan and capecitabine. Based on the observed progression free survival and response rate, the regimen has promising activity. No significant financial relationships to disclose.
Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer
Authors: Moore M. R. , Jones C. , Harker G. , Lee F. , Ardalan B. , Saif M. W. , Hoff P. , Coomes J. , Rollins C. , Felt K. 
Published: March 2020

3591 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center, phase II trial to assess the efficacy of DJ-927 administered initially as second-line therapy following failure of irinotecan or oxaliplatin based therapy (n= 39). DJ-927 is given as a single oral dose on day 1 of a 21-day cycle at a dose range of 27 - 35 mg/m2. Results: Thirty-nine patients were enrolled, including 14 with prior irinotecan based therapy and 25 who had received prior oxaliplatin therapy. The median age was 56 years (range: 30–87) and the median ECOG PS at baseline was 1 (range: 0–2). A total of 155 courses (range: 1–24) have been administered with a median of 2 courses. Nine patients required dose reduction due to toxicity. Thirty-seven patients were evaluable for efficacy. There were 2 CRs and 2 PRs (10.3%) reported that were confirmed as per RECIST criteria. Fourteen patients (35.9%) had SD, including 6 patients (15.4%) with SD >12 weeks. The most common Grade 3 or 4 AEs were neutropenia (48.7%), fatigue (10.3%), neuropathy (7.8%), and nausea (5.0%).Six patients experienced febrile neutropenia, all requiring hospitalization but tolerated treatment with subsequent dose reduction. There were 13 episodes (33.3%) of peripheral neuropathy reported; however, only 3 (7.8%) were grade 3 or 4. Six patients withdrew due to adverse events. Conclusions: The results of this study indicate activity of DJ-927 as second line therapy in patients with metastatic colorectal cancer. Severe toxicity was generally limited to reversible neutropenia and peripheral neuropathy. This novel oral agent is well tolerated and warrants further evaluation in combination with other active agents. [Table: see text]
Pretreatment COX-2 protein expression is a predictor of tumor regression in rectal cancer treated with preoperative short-term chemoradiotherapy
Authors: Kobayashi H. , Hashiguchi Y. , Ueno H. , Shinto E. , Kajiwara Y. , Lenz H. , Danenberg K. D. , Danenberg P. V. , Mochizuki H. 
Published: March 2020

3610 Background: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has become a standard therapy for patients with rectal cancer. However, not all patients have a good response to CRT. Therefore, it is useful to know what the predictor of chemoradiotherapeutic response is. Cumulative evidence has shown that COX-2 has an important role in the progression of colorectal cancer. The aim of this study was to clarify whether pretreatment COX-2 protein expression was a predictor of histopathologic response in patients with rectal cancer treated with preoperative short-term chemoradiotherapy. Methods: Fifty-two patients with lower rectal cancer received short-term preoperative chemoradiotherapy (20 Gy given in 5 daily doses of 4 Gy and administration of Tegafur/Uracil 400mg/day during the same period), followed by total mesorectal excision at National Defense Medical College from 2001 to 2005. COX-2 expression before and after CRT was measured by immunoshistochemistry. The specimens were graded based on the intensity and extent of staining. Tumor regression grading (TRG) was also evaluated (TRG 4, complete regression; TRG 3, regression > 50%; TRG 2, 25% to 50%; TRG 1, < 25%; and TRG 0, no regression). The correlation between COX-2 expression and tumor regression was analyzed. Results: The patient characteristics were as follows: the male:female ratio was 36:16; median age was 62. The Median postoperative follow-up period was 30 months. Two patients had pathological complete response. Good response (TRG 3 + 4) was found in 57.7% of the resected specimens. COX-2 was positive in 80.8% of patients before CRT while in 100% after CRT. The rates of good response (TRG 3 + 4) in patients with and without COX-2 expression were 50% and 90%, respectively (p = 0.021). Conclusions: Patients without pretreatment COX-2 expression were more likely to demonstrate good response to treatment than those with COX-2 expression. Pretreatment COX-2 protein expression can predict response of CRT in patients with rectal cancer. [Table: see text]
Cytokine levels in patients (pts) with localized colorectal cancer (CRC) after surgery and their relationship to fatigue and cognitive function
Authors: Vardy J. , Rourke S. , Galica J. , Pond G. R. , Park A. , Zhang H. , Clarke S. J. , Dhillon H. , Wagner L. , Tannock I. F. 
Published: March 2020

3623 Background: Cytokines have been associated with fatigue and cognitive dysfunction. Here we evaluate cytokine levels in pts with CRC as part of a longitudinal study evaluating these symptoms. Methods: Serum levels of 12 cytokines were measured using a LiquiChip assay on pts with localized CRC at baseline (mean 7 weeks post-surgery or before neoadjuvant therapy), 6 and 12 months. Group A (Stage III/high risk II) received chemotherapy (CT) and group B (Stage I/II) received no CT. Pts completed concurrent questionnaires for fatigue & QOL (FACT-F), anxiety/depression (GHQ), and perception of cognitive function (FACT-COG); they had neuropsychological (NP) assessment with traditional tests and CANTAB, a computerized NP battery. Associations between cytokine levels, test results, demographic and disease-related factors were sought. Results: Baseline data are available for 82 pts: 65 group A and 17 group B, with follow-up at 6 and 12 months for 32 and 15 pts. Mean age was 58 years and 68% were male. Cytokine levels were elevated in all groups with larger ranges after surgery (selected data in table ); in healthy people they are generally undetectable. There was cognitive impairment at baseline in 28% on traditional NP tests. At 6 months CT pts had more fatigue (median FACT-F 43 vs 47), perceived more cognitive impairment (median FACT-COG 127 vs 138), and had more cognitive impairment on CANTAB (42% vs 17%), but not on traditional NP tests (32% vs 33%). At 6 months, elevated cytokines (IL-1,-6,-8,-12, TNF, IFN) were associated with greater deficit on CANTAB (p<0.06); there was no association of cytokines with time from surgery, traditional NP test score, FACT-COG, fatigue, QOL or anxiety & depression. Conclusions: Cytokine levels were elevated in most pts. Cognitive impairment is present in some pts prior to chemotherapy and CT pts have worse impairment on computerized NP tests than non-CT pts. Elevated cytokines may be associated with worse cognitive function. [Table: see text] No significant financial relationships to disclose.
Variation in the cost of treatment for colorectal cancer
Authors: Ferro S. A. , Cosler L. E. , Wolff D. A. , Poniewierski M. S. , Culakova E. , Khorana A. A. , Lyman G. H. 
Published: March 2020

3625 Background: Recent publications have drawn attention to the escalating costs of drugs utilized for the treatment and supportive care of colorectal cancer (CRC) patients. As more advanced chemotherapeutic and supportive agents are approved, the cost of treatment will likely continue to increase. The goal of this analysis was to estimate costs of frequently used CRC chemotherapeutics and other commonly prescribed agents. Methods: Costs of drugs in CRC regimens for patients participating in a prospective, observational study from 115 community oncology practices between March 2002 and March 2005 were calculated. Standard dosages and schedules were determined through literature review and an expert CRC oncologist. Trimmed mean (90%) costs were computed using average wholesale prices (AWP) retrieved from the Lexicon Database Drug Product (January 2005). All prices noted are 95% AWP. All chemotherapeutic drugs were combined to arrive at regimen specific prices. Other regimens were defined as regimens with less than four patients. Price per cycle was estimated based on a standard patient BSA of 2.0 m2 and standard regimen schedules. Growth factor costs were derived from expected per cycle utilization, while prices for other supportive drugs were calculated using dosages for single events. Results: Patients were categorized into the following regimens ( table below). The price of a commonly used monoclonal antibody is: Bevacizumab ($2613), based on every 2 week dosing. Growth factor prices (per cycle) were estimated: Filgrastim ($2499), Pegfilgrastim ($2928), Epoetin ($552), and Darbepoetin Alfa ($1002). Prices per event for other commonly used agents were: Atropine ($245), Loperamide ($3), Ondansetron ($931), and Granisetron ($232). Conclusions: Prices of CRC regimens vary considerably, with newer agents and supportive drugs adding substantially to costs, particularly in late stage disease. Research on improved outcomes or treatment benefits associated with high cost treatment is warranted. [Table: see text] [Table: see text]
Amplification of HER-2/neu (erbB2) gene expression in gallbladder (GBC) and in bile duct cancer (BDC) (biliary tract cancer, BTC)
Authors: Kawamoto T. , Thomas M. , Tarco E. , Trivedi S. , Wistuba I. , Krishnamurthy S. 
Published: March 2020

4011 Background: GBC and BDC (BTC) are uncommon in the United States, but are endemic in parts of South America and Asia. BTC are aggressive tumors with poor survival rates. Chemotherapy RR is <30%, and no survival benefit has been demonstrated. Improved understanding of the molecular carcinogenic mechanisms of BTC may lead to improved therapeutic regimens. Activation of HER-2/neu play a prominent role in the development of breast cancer. In this study, BTC patient (pt) specimens from the U.S., Chile, and Japan were examined the HER-2/neu immunohistochemical (IHC) expression and its gene amplification by fluorescence in situ hybridization (FISH). Methods: Specimens from 26 GBC patients (Chile, US), 12 BDC (USA), 6 cholecystitis (Chole.) (Japan) and 7 normal GB (Chile) were examined. pStage (AJCC) of the pt was: IA: 2, IB: 9, IIA: 7, IIB: 9, III: 3, IV: 4, unknown: 4. Histologic grade was G1 and G2 adenocarcinoma (adca): 22, G3 adca: 13, squamous cell carcinoma: 1, unknown: 2. All cases were screened for HER-2/neu by IHC (0–3+). HER-2/neu gene amplification (FISH (+)) (defined as a HER-2/CEP17 ratio of 2.0 or greater) was performed by double color Her-2/neu gene/chromosome 17 centromere (CEP17) FISH assays using PathVysion HER-2/neu DNA probe kit. Results: In BTC, HER-2/neu IHC 0, 1+, 2+ and 3+ scores were found in 0 (0%), 20 (53%), 11 (29%) and 7 (18%), respectively. In Chole., 3 of 6 (50%) showed 1+ while the remaining and normal GB were all negative for IHC. FISH on paraffin sections was considered successful on 36 (95%) of the 38 cases. HER-2/neu FISH (+) was detected in 7 of 36 (19%) (6 from 3+ cases and 1 from 2+ case) and none in Chole. and normal GB. There was a significant correlation between overexpression by IHC (2+ and 3+) and FISH (+) (Fisher’s exact test; P=0.0123), but no significant correlation between pStage, histologic grade and FISH (+). Conclusions: The HER-2/neu amplification was identified in 19% of BTC in comparison with the other organ cancer (breast cancer:20–25%, lung cancer: 4.5%, colorectal cancer; 2.4%, prostate cancer: 9.3%). There was a strong correlation between IHC overexpression and FISH (+). These data support therapeutic approaches using HER-2/neu targeted agents in BTC pt. HER-2/neu IHC may be a useful surrogate for its gene amplification. No significant financial relationships to disclose.
A randomized phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis
Authors: Kindler H. L. , Bylow K. A. , Hochster H. S. , Friberg G. , Micetich K. , Locker G. , Kozloff M. , Moore M. , Sun W. , Vokes E. E. 
Published: March 2020

4040 Background: In a phase II trial of G + anti-VEGF antibody B in 52 PC pts, we reported a 21% response rate and median survival of 8.8 months (mo) (Kindler, JCO 2005). EGFR inhibitors C and E also have activity in PC. VEGF and EGFR pathways are interdependent; dual inhibition may be synergistic. Methods: We are conducting a multi-center, randomized phase II trial of GBC vs. GBE in advanced PC pts who have: no prior therapy for metastatic disease, PS 0–2, measurable disease, no tumor invasion of duodenum, no bleeding risk. Primary endpoint: response. Trial design: 2 parallel, Simon 2-stage designs; requires 6 responses in 27 evaluable pts for 2nd stage; 63 pts/arm. All pts receive G 1000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg D 1, 15 Q28D. Pts are randomized to C 400 mg/m2 D1, then 250 mg/m2 Q7D, or E 150 mg D1–5, 8–12, 15–26 Q28D. CT scans: Q2 cycles. 58 pts enrolled at 13 sites 9/04–12/05. Pt characteristics: male 66%; median age 61 (range 36–82); PS: 0/1/2: 52%/40%/8%; stage IV 95%; liver metastases 76%. Results: 49 pts (GBC/GBE 24/25) are evaluable for toxicity; 51 pts (27/24) for response. 232 cycles were administered (median 4, range 1–11). Grade ¾ toxicity (%pts GBC/GBE): neutropenia 29%/28%; anemia 4%/16%, thrombocytopenia 8%/24%, DVT-PE 17%/8%, CVA 4%/4%, GI bleed 4%/12%, hypertension 4%/4%, rash 13%/4%, pneumonitis 0%/8%, diarrhea 4%/4%; grade 5: bowel perforation 0%/4%, MI- CVA 0%/4%, other cardiac 4%/0%. Response: GBC 19% (1 complete, 4 partial), GBE 21% (5 partial). Stable disease 59%/67%. Median progression-free survival 3.6/3.6 mo (95%CI: 2.7, 4.7/2.7, 5.9), 6-month survival 41%/38% (95% CI: 11%, 71%/2%, 75%). Conclusion: GBC and GBE are active in advanced PC. Toxicity, principally related to B, is moderate. The trial proceeds to a 2nd stage if 1 more response is observed in each arm. Supported by NCI grant N01-CM-17102. [Table: see text]
18FDG-PET in targeted therapy with cetuximab in gastric or gastroesophageal junction (GEJ) adenocarcinoma: First results of the Italian FOLCETUX Study
Authors: Di Fabio F. , Pinto C. , Fanti S. , Rojas Llimpe F. L. , Longobardi C. , Nanni C. , Funaioli C. , Ambrosini V. , Sperandi F. , Martoni A. A. 
Published: March 2020

4061 Background: The aim of the study was to evaluate 18FDG-PET impact in gastric or GEJ cancer patients (pts) treated with cetuximab plus chemotherapy. Methods: Pts with stomach or GEJ unresectable/metastatic adenocarcinoma, not yet treated, EGFR+, were enrolled in the FOLCETUX study. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, CPT11 180 mg/m2 iv d1, LFA 100 mg/m2 iv followed by 5FU 400 mg/m2 iv bolus and 600 mg/m2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Anti-tumor activity was assessed by CT and PET scan at baseline and then every 6 weeks. A decrease in tumor FDG-uptake (metabolic response) was evaluated according to EORTC recommendations; objective response (OR) was evaluated with CT scan according to the RECIST criteria. Results: From November 2004 to December 2005, 22 pts (16M, 6F) performed at least 2 consecutive PET scans (at baseline and after 6 weeks), with a total of 91 PET scans (median per pts 4; range 2–8). PET was positive in 20 pts (90.9%); no FDG uptake was seen in 2 pts (9.1%) with signet ring cell carcinoma. A metabolic response correctly predicted: CR/PR in 10/12 pts (83%) after 6 weeks of therapy and in 11/12 (91.7%) after 12 weeks; SD in 4/8 pts (50%) after both 6 and 12 weeks. On the whole, response to therapy was predicted by PET after 6 weeks in 14/20 pts (70%). No correlation was demonstrated between median Standardized Uptake Value (SUV) at baseline PET and OR: 10.9 (3–29) in CR/PR pts and 9.6 (6.4–29.8) in SD pts. In the PET scan after 6, 12 and 18 weeks, the median SUV value respectively decreased to 4.4, 2.6 and <2.0 in CR/PR pts and to 7.5, 7.4 and 3.6 in SD pts. The percentage of SUV reduction after 6 weeks was 54.2 in CR/PR pts vs 30.3 in SD pts (p = 0.36); no difference was observed between intestina (55%) and non-intestinal (45%) subtypes. No significant correlation was observed between the Ki-67 and SUV value. Conclusions: These preliminary results suggest that PET can make an early prediction of the response to cetuximab plus FOLFIRI therapy. No significant financial relationships to disclose.
Phase II multicenter trial of docetaxel+oxaliplatin in stage IV gastroesophageal and/or stomach cancer
Authors: Richards D. A. , Wilfong L. , Reznick D. , McCollum D. , Boehm K. A. , Zhan F. , Asmar L. 
Published: March 2020

4071 Background: The treatment of adenocarcinoma of the gastroesophageal junction /stomach (AGEJ/S) remains a therapeutic challenge. This study was conducted to explore the efficacy and safety profile of the combination of docetaxel+oxaliplatin in patients with previously untreated advanced AGEJ/S. Docetaxel has shown significant single-agent activity and has recently been shown to increase response rates and overall survival when combined with cisplatin plus 5-FU. Oxaliplatin is associated with a more favorable safety profile compared to other platinum-based drugs (ie, cisplatin). Methods: Patients with metastatic (Stage IV) AGEJ/S were eligible. Treatment consisted of docetaxel 60 mg/m2 over 1 hour IV followed by oxaliplatin 130 mg/m2 over 2 hours on Day 1 of each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity; primary endpoints are response rate, toxicity, and progression free and overall survival. Results: We have enrolled all planned eligible patients (N = 71). Baseline characteristics include a median age of 59.5 years, 72% male patients, 76% white, and ECOG PS scores 0/1/2 of 45%/49%/6%, respectively. 32.8% of patients had distal gastric cancer (fundus or pylorus). The median number of cycles delivered to date is 6 (range, 1–14). Twenty patients (31%) have required dose reductions primarily due to neutropenia. Grade 3–4 toxicities include neutropenia (69%); vomiting (17%); nausea (16%); dehydration, fatigue, and diarrhea (13%, each), and thrombocytopenia and febrile neutropenia (7%, each). Sixty-six patients have completed ≥2 cycles. The best overall confirmed response rate, by RECIST, was 24 PR (35.6%) for an overall response rate of 35.6%. Median time to response was 2.4 months and median duration of response was 4.1 months. Median survival was 9.2 months and median PFS was 4.4 months. Conclusions: The combination of docetaxel and oxaliplatin is associated with manageable toxicity in this group of patients with AGEJ/S. The best overall response rate of 35% and median survival of 9.2 months is encouraging and comparable to other standard front-line regimens. This research was supported, in part, from a research grant from sanofi-aventis. [Table: see text]