bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health care utilization and economic burden of dermatologic adverse drug reactions (ADRs) in patients with colorectal cancer treated with an epidermal growth factor receptor inhibitor (EGFRI).
Authors: Bonthapally Vijayveer , Guerin Annie , Wu Eric Q. , Gauthier Genevieve , Holen Kyle D. , Ray Saurabh 
Published: February 2017

584 Background: Colorectal cancer patients with EGFRI therapies may develop dermatologic ADRs. ADRs negatively affect patients’ quality of life, require medical care, and may lead to a substantial economic burden. The objective of this study is to assess the economic burden of dermatologic ADRs in patients with colorectal cancer (CRC). Methods: Continuously enrolled adult patients with ≥ 1 CRC diagnosis initiated on an FDA-approved EGFRI therapy (i.e., cetuximab, panitumumab) were selected from a large US claims dataset. Patients were classified into two mutually exclusive cohorts depending on whether or not they had dermatologic ADR during the period following EGFRI initiation. Dermatologic ADRs were identified using ICD-9-CM codes. Patients were observed from the index date up to the end of the health plan enrollment, or data availability, or 90 days after the EGFRI discontinuation, whichever occurred first. Incidence rate ratios (IRRs) for healthcare resource utilization were estimated using Poisson regression models. Incremental costs (2010 USD) were estimated on a monthly basis using generalized linear or two-part models. Multivariate regressions controlled for age, gender, comorbidities, and baseline healthcare utilization and costs. Results: A total of 746 and 1,720 patients were included in the dermatologic ADR and ADR-free cohorts, respectively. After adjusting for confounding factors, compared to patients in the ADR-free cohort, patients in the ADR cohort had higher incidence of emergency room visits (IRR=1.2; p=.009) and higher incidence of outpatient visits (IRR=1.13; p<.001). Moreover, patients in the ADR cohort incurred higher total healthcare costs by $2,532 (p=.009) per patient per month mainly due to higher emergency care costs by $566 (p<.001). Conclusions: Compared to ADR-free patients, dermatologic ADR patients with colorectal cancer incurred a substantial economic burden related to higher healthcare resource utilization and costs. Efforts to improve the dermatologic side effect profile of EGFRI are needed to control this burden.
Updated survival results of the randomized phase II study of S-1, oral leucovorin, and oxaliplatin combination therapy (SOL) versus mFOLFOX6 in patients with untreated metastatic colorectal cancer (mCRC).
Authors: Otsuji Toshio , Yamazaki Kentaro , Ojima Hitoshi , Kuwano Hiroyuki , Kato Takeshi , Shimada Ken , Denda Tadamichi , Esaki Taito , Hyodo Ichinosuke , Boku Narikazu 
Published: February 2017

586 Background: We previously reported short term results of a randomized phase II study comparing SOL with mFOLFOX6 in terms of progression-free survival (PFS) by central review. The median PFS for SOL and mFOLFOX6 was 9.6 and 6.9 months (HR= 0.83; 95%CI, 0.49-1.40) with median follow-up time 14 months (Ojima et al, ESMO 2011). Here, we report updated overall survival (OS) results with 29 months follow-up. Methods: The inclusion criteria were; 1) histologically proved adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (Pts) were randomized to receive either S-1 (40-60 mg bid) and oral LV (25 mg bid) for one week and L-OHP (85 mg/m2) on day 1, repeated every 2 weeks (SOL; Group A) or L-OHP (85 mg/m2), l-LV (200 mg/m2), and 5-FU (400 mg/m2, bolus) on day 1, followed by 5-FU (2400 mg/m2, ci, 46 hours), repeated every 2 weeks (mFOLFOX6; Group B). This trial was supported by Taiho Pharmaceutical CO., LTD and Yakult Honsha CO., LTD. ClinicalTrials.gov Identifier: NCT00721916 Results: From July 2008 to July 2009, 107 pts were randomized, and 105 were eligible (56 to Group A and 49 to Group B). When survival data were updated 2 years after the last patient’s enrollment, with no lost cases, median OS for Group A and Group B was 28.5 and 25.9 months (HR= 0.76; 95%CI, 0.45-1.31), 2-year survival rate was 71.4% and 59.2%, respectively. The incidences of grade 3/4 adverse drug reactions were; neutropenia (19.6% Group A, 41.2% Group B), lymphopenia (14.3% and 5.9%), sensory neuropathy (19.6% and 2.0%), anorexia (12.5% and 7.8%), fatigue (10.7% and 5.9%) and diarrhea (10.7% and 3.9%). Post treatments with or without molecular target agents were performed for 80.4 % of Group A, and 75.5 % of Group B. Conclusions: The results of the present analysis show that SOL might be more effective than mFOLFOX6 in terms of both PFS and OS as the first line chemotherapy for mCRC. Further investigation of the SOL regimen, a phase III trial of its combination with molecular target agents should be considered.
Randomized phase II study of oxaliplatin and S-1 (OS) versus oxaliplatin and capecitabine (XELOX) in patients with advanced or recurrent colorectal cancer.
Authors: Zang Dae Young , Chung Ik-Joo , OH HO-Suk , Park Keon Uk , Lee Kyung Hee , Han Boram 
Published: February 2017

595 Background: Combination oxaliplatin and S-1 or oxaliplatin and capecitabine chemotherapy have shown significant efficacy in advanced colorectal cancer. To evaluate those efficacy and safety, we performed a randomized phase II study in patients with metastatic or recurrent colorectal cancer. Methods: Eligible patients were those who had measurable lesions and had no previous history of chemotherapy except adjuvant chemotherapy. The patients of age greater than 18 were enrolled to this study. Oxaliplatin 130 mg/m2 was administered intravenously on day 1 and S-1 80 mg/m2 (OS, Arm A) or capecitabine 2,000 mg/m2 (XELOX, Arm B) was administered orally on days 1-14. Cycles were repeated every 21 days. Patients were treated until proved to have disease progression or unacceptable toxicity. The primary endpoint of the study was to assess the overall response rate (ORR). Results: Eight-two patients (male/ female 57/ 31; median age 67, range 29-83; median ECOG PS 1; Arm A/ B 43/45) were enrolled to this study. Twenty-five patients had recurred cancer after surgery and 63 patients were diagnosed as metastatic diseases. A total of 268 cycles (median 5, range 1-34) in Arm A; 278 cycles (median 5, range 1-18) in Arm B were administered. Eighty-two (41 for each arm) patients were evaluated for toxicity and response. The main toxicities were thrombocytopenia [grade 1/ 2/ 3/ 4 = 11/ 7/ 6/ 1 patients (A); 9/ 10/ 7/ 5 (B)], neutropenia [grade 1/ 2/ 3/ 4 = 8/ 6/ 1/ 0 (A); 9/ 9/ 5/ 2 (B)], anemia [grade 1/ 2/ 3/ 4 = 21/ 13/ 3/ 1 (A); 20/ 10/ 3/ 0 (B)], peripheral neuropathy [grade 1/ 2/ 3 = 11/ 8/ 0 (A); 10/ 8/ 2 (B)], and hand-foot syndrome [grade 1/ 2/ /3 = 2/ 0/ 0 (A); 7/ 1/ 2 (B)]. There were 3 CR, 10 PR, 27 SD and 1 PD (A); 3 CR, 15 PR, 17 SD and 6 PD (B). The confirmed ORR in the intention-to-treat population was 30.2 (95% CI: 16.5-43.9) % (A); 40.0 (95% CI, 25.7-54.3) % (B). The median time to progression was 6.6 (95% CI, 4.4-8.8) months (A); 8.1 (95% CI, 6.3-10.0) months (B). The median survival time was 19.0 (95% CI, 7.3-30.8) months (A); 22.0 (95% CI, 12.1-32.0) months in (B). Conclusions: These data suggest that both OS and XELOX regimen are active and are well tolerated regimens in patients with advanced colorectal cancer.
Induction chemotherapy followed by chemoradiotherapy and TME for high-risk locally advanced rectal cancer with and without synchronous resectable metastases.
Authors: Hajj Carla , Weiser Martin R. , McErlean Aoife , Gollub Marc , Cercek Andrea , Ding Pei-Rong , Saltz Leonard , Goodman Karyn A. 
Published: February 2017

599 Background: Induction chemotherapy (ICT) followed by chemoradiation (CRT) may improve tumor downsizing and disease control among patients (pts) with locally advanced rectal cancer (LARC). We retrospectively assessed the safety and short-term efficacy of ICT followed by CRT and total mesorectal excision (TME) in pts with high-risk LARC with or without synchronous resectable metastases. Methods: We reviewed records of 44 consecutive stage III (n=23) or stage IV synchronous (n=27) pts with LARC treated with ICT followed by CRT between 12/06 – 12/10. Pts had high-risk primary tumors based on advanced T and/or N stage by endorectal ultrasound and/or MRI: T3 (n= 35), T4 (n=7) and N1 (N=18), N2 (n=19). Recurrence-free (RFS) and overall survival (OS) were estimated by Kaplan-Meier methods. Results: Median age was 52 yrs, 66% were female. Pts received a median of 6 cycles of 5-FU based ICT combined with oxaliplatin (n=44). CRT (median dose 50.4 Gy) was delivered with continuous infusion 5-FU; two pts did not complete the prescribed CRT. During induction CT, 10 (22.7%) pts experienced grade 3+ neutropenia. Grade 3+ neutropenia or GI toxicity occurred in 3 (6.8%) and 3 (6.8%) pts, respectively during CRT. Imaging or endoscopic assessment showed that 35 pts had disease regression after ICT, whereas 1 pt progressed and 2 had stable disease. Response to ICT was not assessed in 6 pts. 7 pts did not undergo surgery due to: progression of disease (n=2); comorbid disease (n=2); or pt refusal (n=3). 37 pts proceeded to TME including 17 with known distant metastasis, 16 of whom underwent metastasectomy. 17 pts had tumor response > 90% including 8 with pathologic CR. With a median follow-up of 29.4 mos, 1 pt who underwent TME developed local recurrence. Amongst the 9 pts who had distant recurrences, 7 had initial stage IV disease. The 3-yr RFS among the resected stage III pts was 95%; the 3-yr OS for stage III pts and stage IV pts were 100% and 80% respectively. Conclusions: In this retrospective series, ICT prior to CRT was associated with acceptable toxicity and a substantial incidence of tumor regression. OS and RFS appear promising in this high-risk group of patients.
HER2 evaluation in a specific gastric cancer population with the highest rate of mortality in Spain.
Authors: Una Cidon Esther 
Published: February 2017

60 Background: Gastric Cancer (GC) still represents the second cause of cancer-related death worldwide. Radical resection is the mainstay of early stages treatment with few impact in overall survival (OS) in the advanced ones. HER-2 is the most relevant biological factor involved. Purpose: This study aims to show the relationship between HER-2 positivity and survival in patients with completely resected GC. Methods: Retrospective study of GC patients diagnosed in 2003-2005 at our institution. Surgical specimens underwent immunohistochemistry (IHC) and in cases +/++/+++ samples underwent also fluorescence in situ hibridysation (FISH) analyses of HER-2 and graduated according experts consensus. Results: 120 cases included. Overall expression detected in 7.5%. Correlation between HER-2 positive and female sex, advanced stages or histological grades or intestinal type was detected. Early recurrences higher in HER-2 positive (66.6% vs 35.4%, p 0.048). The median DFS for c-erbB-2 positive was 15 months (range 2-67 months) and OS was 25 months (range 10-67 months). In the case of patients with c-erbB-2 negative median DFS was 27 months (range 5-67 months) and OS for this sample is 47 months (range 29-67 months). Conclusions: These results emphasize the relevance of HER-2 positivity in GC as independent prognostic factor and supports its current analyses in daily practice.
Phase I study of mFOLFOX-6, bevacizumab, and mTOR inhibitor RAD001 as first-line treatment of metastatic colorectal cancer.
Authors: Gilcrease Glynn Weldon , Weis John R. , Jones Kimberly , Davis Thaylon , Mitchell Marlene , Davidson Cynthia , Sharma Sunil 
Published: February 2017

600 Background: This study was designed to determine the dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), and efficacy of the mTOR inhibitor RAD001 in combination with mFOLFOX-6 and bevacizumab in metastatic colorectal cancer. Methods: Twenty patients with previously untreated metastatic colorectal cancer received mFOLFOX-6, bevacizumab and RAD001 using a standard three patient cohort dose escalation schema. Seventeen of the twenty patients were evaluable with a median age of 52 (ten females and seven males). RAD001 was administered orally at escalating doses of 2.5 mg, 5 mg and 10 mg daily. mFOLFOX-6 and bevacizumab were administered in standard fashion. Results: The most common grade 3/4 hematological adverse events (AEs) were neutropenia (59%), leucopenia (29%) and thrombocytopenia (12%). The most common grade 3 non-hematological AEs were diarrhea (24%) and hypokalemia (18%). One dose-limiting toxicity was noted at 10 mg/day due to grade 3 anorexia, grade 3 diarrhea, and grade 3 hypokalemia. Grade 1 mucositis was noted in 12% of patients and grade 2 mucositis was noted in 47% of patients. There was no grade 3/4 mucositis. Fourteen patients are evaluable for efficacy. The RR is 86% including 2 CRs, 7 PRs, and 3 SDs. Conclusions: RAD001 in combination with mFOLFOX6 and bevacizumab is well-tolerated at a dose of 10 mg/day. The regimen appears to be effective. Evidence of anti-tumor activity correlated with mutation status (k-ras, BRAF, PIK3CA) and PTEN deletion status will be presented.
Efficacity and safety of panitumumab in mCRC patients: A post-AMM OMIT study.
Authors: Grude Francoise , Ramée Jean François , Guivarch Laurent , Douillard Jean-Yves , Rochard Sophie , Dupuis Olivier , Grollier Chrystelle , Guerin-Meyer Veronique , Leynia Pierre , Porneuf Marc , Peguet Elodie , Raoul Jean Luc , Bertrand Claude , Deguiral Philippe , Derenne Laurent , Achour Nacredine , Person Bernadette , Metges Jean-Philippe , Lebot Marie-Annick , Riche Christian 
Published: February 2017

608 Background: Metastatic colorectal cancer (mCRC) management has been improved by targeted therapies. The evaluation of the use of panitumumab (PANI), after approval, in the real life is strategic to assess health politics. OMIT Bretagne - Pays de Loire is a network of private and public cancer centers. Methods: Data from patients treated with PANI in mCRC were collected. Previously published data are recited. Sex, age, primary tumor, Kras status, line of treatment, toxicity, reason of discontinuation, response, progression free survival (PFS) and overall survival (OS) have been studied. Results: Data of 322 patients treated between second half of 2008 and end of 2010 have been collected. PANI was used alone (85.5%) or with chemotherapy (14.5%) : mainly FOLFIRI, IRINOTECAN or FOLFOX). KRAS status was wild-type (WT 96.5%), mutated (0.5%), undetermined (2.5%) or not searched (0.5%). Only KRAS WT patients treated with monotherapy of PANI at 6 mg/kg every 2 weeks were analysed (n=263). Sexe : 177 men and 86 women. Median age : 67 years [36-90] (Van Custem JCO 2007: 62 years [27-83]). Primary tumor of patients was : colon (75%), rectum (22%) and others (3%). They received PANI mostly at line 2 (25%), 3 (46%) or 4 (19%). Discontinuation of treatment was mostly due to disease progression : 64%, death: 15% and toxicities : 7% (skin toxicities 3.7%). Clinical response was evaluated for the first 84 patients: partial response (PR): 30%, stable disease (SD): 14% and progression (P): 56%. In KRAS WT patients treated by PANI, Amado described 17% of PR, 34% of SD and 49% of P (Amado JCO 2008). Median duration of treatment was 69 days [0;360] (n=249). Median duration between end of treatment and death when death is the cause of end of treatment was 13 days [0;54] (n=35). Median of OS was 137 days [0;816] (n=143) which is lower than previously described (Van Cutsem JCO 2007 : 192 days regardless of KRAS status ; Amado JCO 2008 : 243 days in KRAS WT). Conclusions: The OMIT analysis of patients treated by PANI in Bretagne/Pays de Loire for a mCRC allows to assess the good use, according to its label, in the real life. Complete results about clinical response, PFS (cut-off 01/12/2011), OS and safety as well as previously published data will be shown at the meeting.
Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).
Authors: Kato Takeshi , Nishina Tomohiro , Yamazaki Kentaro , Yoshino Takayuki , Miyata Yoshinori , Esaki Taito , Moriwaki Toshikazu , Hyodo Ichinosuke 
Published: February 2017

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330-1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).
The role of palliative resection in metastatic colorectal cancer: 10 years of experiences from a single institute.
Authors: Park Jin Hyun , Lee Kyung-Hun , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kang Gyeong Hoon , Chie Eui Kyu , Jeong Seung-Yong , Park Kyu Joo , Park Jae-Gahb , Kim Tae-You 
Published: February 2017

626 Background: Systemic chemotherapy is still mainstay of treatment of metastatic colorectal cancer (mCRC), while the role of palliative resection is not convincing. We intended to find out the role of palliative resection in mCRC. Methods: A total of 1,015 patients were diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009. Except 169 patients who received curative metastectomy of liver and/or lung, 847 patients were retrospectively analyzed. Results: Out of 847 patients, 556 (65.6%) had metastasis at the time of diagnosis and 291 (34.4%) had recurrence after surgery. The median age was 61 (range, 16-88) and 491 (58.0%) were male. The median number of metastatic site was 1 (range, 1-6) and 738 (87.1%) had limited metastasis (number of metastatic site ≤2). The liver was most frequently involved site (451, 53.2%). Surgery was done in 527 (62.2%). One hundred three patients received resection of both primary and metastatic sites (group 1), while 347 and 78 received resection of primary (group 2) and metastatic sties (group 3), respectively. R0 resection was done in 95 patients (G1: 53, G3: 42), while R1/2 was done 431 in patients (G1: 56, G2: 336, G3:39). Of 95 patients with R0 resection, 93 (97.8%) had limited metastasis (number of metastatic organ ≤2) in the peritoneum, lymph nodes, liver, or lung. The median overall survival (OS) was 19.0 months (95% CI, 17.8-20.1) and resected patients had prolonged median OS compared with patients never resected (21.3 vs 14.1 months, p < 0.001). In multivariate analysis, R0 resection was associated with superior OS compared to R2 resection (51.3 vs 18.7 months; HR, 3.0; 95% CI, 1.86 to 4.85, P<0.001), and no resection (51.3 vs 14.1 months; HR, 2.93; 95% CI, 1.73 to 4.96, P<0.001). Palliative chemotherapy was administered in 746 (88.1%), while chemotherapy was not performed in 101 (11.9%) due to patient’s refusal and poor performance status. In multivariate analysis, chemotherapy was also independent prognostic factor for OS (20.4 vs 5.4 months, HR, 3.47; 95% CI, 2.25 to 5.35, P<0.001). Conclusions: Palliative resection with curative intent and chemotherapy confer long-term survival on subsets of mCRC with limited metastasis.
Role of biologic therapy in the treatment of unresectable appendiceal epithelial neoplasms (AEN).
Authors: Eng Cathy , Overman Michael J. , Fournier Keith F. , Royal Richard E. , Ohinata Aki , Rafeeq Safia , Phillips Jonathan , Wolff Robert A. , Mansfield Paul F. 
Published: February 2017

628 Background: AEN ranges from benign appearing cells to poorly differentiated signet cell adenocarcinoma. Currently, cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is believed to be optimal treatment. Systemic chemotherapy (SC) +/- biologic therapy (BT) is considered when CRS is not feasible. VEGF expression reportedly is a poor prognostic indicator in AEN pts. The purpose of this analysis is to determine the benefit of BT in chemotherapy naïve suboptimal candidates for CRS. Methods: A retrospective chart review of AEN pts registered in our tumor registry between Jan. 2005 to Dec. 2009 was undertaken. Electronic medical records (EMR) were reviewed for CRS, HIPEC, histology, stage, SC + BT, CEA, CA-125, and/or CA 19-9, response (R), and progression-free survival (PFS). All patients were required to be radiographically restaged at MDACC. R was defined as clinical or radiographic benefit. K-M method, Log-Rank, and Cox proportional hazard regression models were used for statistical analysis. Results: Of 625 pts with a diagnosis of AEN, 132 (21%) fulfilled the inclusion criteria and were evaluable for PFS and R. Sixty-five (49%) pts received SC + BT; 67 (51%) pts received SC alone. SC included: 5-FU = 28 (21%), FOLFIRI = 20 (15%), FOLFOX = 71 (54%), and other = 13 (10%). BT included: bevacizumab = 58 (89%), EGFR inhibitor = 6 (9%); 1 pt (2%) received both. Median lines of BT = 1 (range: 1-3). Histologically, 51 (38%) were poorly differentiated and 33 (25%) were signet ring; 26 (20%) had both features. After a median follow-up of 33M, 40 (62%) had stable disease, 12 (19%) partial response, and 12 (19%) progressive disease. Biologic therapy improved median PFS and OS (17M vs. 7M, p-value = 0.007; 68M vs. 50M, p-value = 0.08, respectively). Multivariate analysis indicated improved PFS (HR: 0.49; 95% CI: 0.3-0.8; p-value: <0.001) and OS (HR: 0.52; 95% CI: 0.3-0.8; p value = 0.007) in favor of biologic therapy. Conclusions: Biologic therapy in combination with chemotherapy appears to have a role in surgically unresectable AEN pts with improvement in PFS and OS. Tissue/blood correlatives and quality of life analysis are underway. Prospective analysis including cost-benefit should be considered.