bluuebunny/crossref_metadata_2025_split huggingface dataset:
X-TRAP: Phase I/II study of capecitabine (X) plus ziv-aflibercept (TRAP) in metastatic colorectal cancer (mCRC).
Authors: Strickler John H. , Rangwala Fatima A. , Rushing Christel , Niedzwiecki Donna , Altomare Ivy , Uronis Hope Elizabeth , Hsu Shiaowen David , Zafar Yousuf , Morse Michael , Chang David Z. , Wells James Leroy , Blackwell Kimberly L. , Marcom P. Kelly , Webb Anna Renee , Dropkin Evan , Arrowood Christy , Hurwitz Herbert 
Published: February 2017

687 Background: Patients (pts) with chemotherapy refractory mCRC have a poor prognosis, with a median survival of approximately 6 months (mos). Ziv-aflibercept is FDA-approved in combination with FOLFIRI for the 2nd line treatment of mCRC, but its tolerability and activity in pts with chemotherapy refractory disease is unknown. We designed a phase I/II study of X+TRAP to define the recommended phase II dose (RPTD), and assess the safety, tolerability, and clinical activity for the combination. Methods: Eligible pts with refractory, advanced solid tumors were enrolled in a 3+3 dose escalation cohort (ESC) to identify the RPTD. Cycle length was 21 days. Radiographic assessment occurred every 3 cycles. X was administered po bid on days 1-14. The dose of X was 850 mg/m2 bid in ESC cohort 1 and 1,000 mg/m2 bid in ESC cohort 2. TRAP was administered on day 1 of each cycle (6 mg/kg IV). Pts with mCRC that had progressed on all standard therapies were then enrolled in a single-arm, phase II expansion cohort (EXP) and treated at the RPTD. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Results: As of 6/19/2015, 55 pts were evaluable for toxicity (13 ESC; 42 EXP) and 47 pts were evaluable efficacy (12 ESC; 35 EXP). In the phase I ESC cohorts, 3 DLTs occurred (1/6 cohort 1; 2/6 cohort 2): GI perforation (1), oral mucositis (1), and fatigue (1). The RPTD was X (850 mg/m2 po bid, days 1-14) and TRAP (6 mg/kg IV, day 1). In the ESC and EXP cohorts, there were no treatment related grade 4/5 adverse events (AEs). The most frequently reported treatment related AEs (grades 2+3; grade 3) were palmar-plantar erythrodysesthesia (36%; 5%), hypertension (29%; 20%), and oral mucositis (18%; 4%). Median follow up in the phase II EXP cohort was 9.3 mos (95% C.I., 6.5–11.1). Median PFS was 4.1 mos (95% C.I., 2.3-4.8). Response assessment in 35 pts (n; %): partial response (PR) (2; 6%); stable disease (SD) (12; 34%); SD > 6 mos (2; 6%). Median OS was 9.3 mos (95% C.I., 6.2–n/a). Conclusions: The combination of X+TRAP demonstrated an acceptable safety profile, with encouraging clinical activity at the RPTD. Recruitment for the phase II EXP cohort is now complete. Clinical trial information: NCT01661972.
Longitudinal follow-up of quality of life in gastrointestinal cancer patients after curative surgery in South Korea.
Authors: Zang Dae Young , Jung Hyun Ae , Han Boram , Kim Jung Hoon , Choi Dae Ro , Kim Hyeong Su , Jang Geundoo , Kwon Jung Hye , Kim Ho Young , Kim Jung Han , Jung Joo Young , Kim Hyo Jung , Yoon Hyunsook , Park Young Suk , Lee Hyun Woo , Kang Seok Yun , Cho Ji Woong , Song Hun Ho 
Published: February 2017

697 Background: Early detection of cancer and improved treatment have led to higher survival rates and an increasing number of long-term survivors in oncology practice. But there are few longitudinal Quality of Life (QoL) studies in patients who experienced cancer surgery. To investigate the longitudinal change in QoL of elderly gastrointestinal cancer patients, we designed prospective study for QoL in resected gastrointestinal cancer patients. Methods: A prospective longitudinal cohort study was designed. Patients from Hallym, Ajou, and Samsung medical center in South Korea were enrolled consecutively from February to September of 2012. Patients over 55 years old who received curative resection due to gastrointestinal cancer were included. They were given questionnaires every 6 months since then, and we’ve been using EORTC QLQ C-30 as quality of life scale. We selected patients using propensity score matching(PSM). The mean scores of the patients completing the interview at the 3 time points were compared using mixed model. Results: A total of 353 patients with gastrointestinal cancer were interviewed at baseline. We dichotomized patients into 2 groups ( < 70 years old vs. > = 70 years old). There were significant difference in ECOG performance status between 2 groups. After balancing with PSM, we selected 272 patients. Overall QoL did not show significant difference between 2 groups at baseline interview. After repeated interview, the score of global health status, physical functioning, and pain showed significantly higher in younger group ( < 70 years old). But other items didn't show significant difference.Especially patients in both group felt financial difficulty increased. Conclusions: Although the elderly gastrointestinal cancer patients showed lower score in global health status, physical function, they preserved relatively well in other functional status after curative surgery. Most patients felt increased financial burden.
A multicenter phase II trial of mFOLFOX6 plus bevacizumab as treatment for liver-only metastases from colorectal cancer unsuitable for upfront resection (TRICC0808): Final analysis for survival.
Authors: Tamagawa Hiroshi , Uetake Hiroyuki , Ishiguro Megumi , Mizunuma Nobuyuki , Kinugasa Yusuke , Mochizuki Izumi , Hamaguchi Tetsuya , Hasegawa Junichi , Katsumata Kenji , Ishibashi Keiichiro , Ogata Yutaka , Takii Yasumasa , Ooshiro Mitsuru , Kagimura Tatsuo , Sugihara Kenichi ,   TRICC0808 Study Group
Published: February 2017

704 Background: TRICC0808 trial is a phase II trial to evaluate the liver resection rate and safety after mFOLFOX6 + bevacizumab therapy for liver-only metastasis that is unsuitable for upfront resection (H2 and H3) from colorectal cancer. Primary endpoint was the R0 resection rate, which was reported to be 44.4% (Ann Surg Oncol 22: 908-915, 2015). Final analysis of TRICC0808 was performed (February 16, 2015 data fixation). Methods: Forty six patients were registered and OS was analyzed for 45 patients (FAS). In 24 cases with liver resection after protocol chemotherapy, RFS, recurrence rate and recurrence patterns were analyzed. Results: The1, 2 and 3 year OS rate in FAS from the starting date of the chemotherapy was 91.1%, 68.9%, 44.0%, respectively, with 2.80 years of MST. The 3 year OS rate in 31 patients with liver resection including resection after additional chemotherapy was 61.3% with 3.59 years of MST, which was better than 0% of the 3 year OS rate with 1.75 years of MST in patients without liver resection. In 24 who underwent liver resection after 6 cycles of protocol chemotherapy, the 1, 2 and 3 year RFS rate was 29.2%, 12.5%, 8.3%, respectively, with 3.07 years of MST. The recurrence rate for 20 patients with R0 liver resection was 80%, and 100% in those with R1 and R2 liver resection. In the 20 patients with R0 liver resection, the 3 year OS rate of 16 patients with technically resectable liver metastasis at registration and 4 with technically unresectable tumors was 53.6% and 50.0%, respectively. Conclusions: The present final analysis of TRICC0808 trial disclosed good OS in the patients with liver resection, though the large population of the patients recurred afterward. The results were concordant with those of other reported trials for liver metastasis which is unsuitable for upfront resection. Liver resection was thought to be effective for liver metastasis which converted from unresectable to resectable after chemotherapy. Clinical trial information: UMIN000010209.
Systemic therapy in anorectal melanomas: Does choice of systemic therapy matter?
Authors: Singhal Nitin Kumar , Ostwal Vikas S. , Shrikhande Shailesh V. , Saklani Avanish , Arya Supreeta , Ramadvar Mukta 
Published: February 2017

731 Background: Anorectal melanomas are relatively uncommon and there is no consensus on the optimal systemic therapy regime with survival advantage. Methods: Retrospective analysis of prospectively maintained database of patients treated at our institute between January 2102 and July 2015. SPSS 20 used for statistical analysis. The survival benefit was assessed in the form of progression free survival (PFS) and overall survival (OS) with the systemic therapy. Results: Out of 74 anorectal melanoma patients seen during this period 50 patients had metastatic disease and were evaluated for outcome analysis. Median follow up of patients was 8 months. Of these 50 patients, 36 received chemotherapeutic regimes (taxanes with platinums with or without oral metronomic therapy (OMT), dacarbazine/temozolamide or OMT alone) as per the description of treating physician, while 11 patients did not receive any systemic therapy due to poor general condition at presentation, or refused therapy. 3 patients defaulted during the initial work up. Median age at presentation was 54 years and common sites of metastasis were Liver, lung and lymph nodes. Median OS for patients who underwent excision was 22 months. In patients who received systemic therapy median OS was 13 months versus 8 months for those who did not receive it (p = 0.253). The Median PFS after 1st line systemic therapy was 3 months. 5 patients had grade III toxicities in the form of neutropenia, diarrhea. PFS was 3 months for temozolamide/dacarbazine, OMT along with chemotherapy or OMT alone whereas it was 5 months for taxanes with platinum. (p = 0.045). OS was 11 months for OMT with or without chemotherapy and 18 months for taxanes with platinum (p = 0.43). Conclusions: Palliative systemic therapy has some survival advantage in metastatic anorectal Melanomas. Taxanes with platinums appear to be the most efficacious among the presently used regimens even in anorectal melanomas. OMT also has the survival benefit with the advantage of oral therapy in palliative setting
Regorafenib for previously treated metastatic colorectal cancer (mCRC): A subgroup analysis of 364 patients in the USA treated in the international, open-label phase IIIb CONSIGN study.
Authors: Verma Udit , Arriaga Yull Edwin , Lenz Heinz-Josef , Henderson Charles A. , Fuloria Jyotsna , Cartwright Thomas H. , Khojasteh Ali , Stella Philip J. , Saltzman Marc , Cohn Allen Lee , Philip Philip Agop , Kappeler Christian , Kalmus Joachim , Grothey Axel , Van Cutsem Eric , Hochster Howard S. , Arena Francis P. 
Published: February 2017

735 Background: In the phase III CORRECT study, regorafenib significantly improved overall survival and progression-free survival (PFS) vs placebo in patients with treatment-refractory mCRC. CONSIGN (NCT01538680) was a large phase IIIb study that included 2872 patients from 25 countries; it was designed to provide continued access to regorafenib for patients with mCRC who failed standard therapy and to further characterize the safety of regorafenib. In CONSIGN, adverse events (AEs) and PFS were consistent with those reported in phase III studies. We present a retrospective subgroup analysis of patients enrolled in CONSIGN in the USA. Methods: Patients with mCRC who progressed on standard therapies and had an ECOG PS 0─1 received regorafenib 160 mg QD for the first 3 weeks of each 4-week cycle. Treatment was continued until disease progression, death, or unacceptable toxicity. The primary endpoint was safety. PFS (per investigator) was the only efficacy variable assessed. Results: A total of 364 patients in the USA were assigned to treatment (all evaluable for safety). The median age was 60 years; 38% and 62% had ECOG PS 0 and 1, respectively. KRAS mutation was present in 59%, KRAS wt in 38%; 74% had ≥ 3 prior regimens for metastatic disease. Median duration of treatment was 2.3 months (range: 0–30). Median PFS (95% CI) was 2.3 (2.0–2.6) months (2.1 months KRAS wt; 2.3 months KRAS mutant). NCI-CTCAE v4.0 grade ≥ 3 AEs occurred in 81% of patients and were considered drug-related in 53% (Table). Grade ≥ 3 hepatobiliary disorders occurred in 2%. Grade ≥ 3 treatment-emergent laboratory toxicities included bilirubin (9%), AST (6%), and ALT (3%). Conclusions: In patients from the USA enrolled in CONSIGN, the safety profile of regorafenib was consistent with that of the overall population and the known safety profile of regorafenib in mCRC. Median PFS was in the range of that reported in phase III trials. Clinical trial information: NCT01538680. [Table: see text]
Phase II study of irinotecan and bevacizumab plus alternate day S-1 as second-line treatment in patients with metastatic colorectal cancer.
Authors: Tanaka Chihiro , Matsuda Chu , Kondo Ken , Tokunaga Yukihiko , Takahashi Takao , Kosugi Chihiro , Takemoto Hiroyoshi , Iwamoto Shigeyoshi , Oba Koji , Sakamoto Junichi , Mishima Hideyuki 
Published: February 2017

749 Background: The recommended dose of combination chemotherapy of irinotecan, bevacizumab and oral S-1 is 100mg/m2, 5mg/kg and 80-120mg/body respectively. To evaluate whether the dose of irinotecan could be raised to 150mg/m2 with modified administration of S-1, we have conducted a phase II study of irinotecan and bevacizumab plus alternate day S-1 in patients with metastatic colorectal cancer (UMIN000008947). Methods: Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatine and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5mg/kg) were given intravenously on day 1. Oral S-1was administered on alternate days at a dose of 40-60mg twice a day. Cycles were repeated every two weeks. Results: A total of 51 patients were evaluated in the first fouur cycles. Grade 3 and 4 neutropenia were 10% (10/51) and 13.7%(7/10), grade 3 and 4 thrombocytopenia were 0%(0/51) and 2.0% (1/51). Grade 2 and 3 mucositis were 13.7% (7/51) and 3.9% (2/51). Grade 2 and 3 nausea were 11.8% (6/51) and 2.0% (1/51). Grade 2 and 3 diarrhea were 17.6% (9/51) and 15.7% (8/51). The relative dose intensities were 84.8% for irinotecan, 87.5% for bevacizumab, and 84.8% for S-1 respectively in the first four cycles. Conclusions: Our data suggest that irinotecan (150 mg/m2) and bevacizumab was administered safely with alternate day S-1 as second-line tratment in patients with metastatic colorectal cancer. Clinical trial information: 000008947.
Outcomes after resection of pulmonary metastases in patients with colorectal cancer.
Authors: Mi Kaihong , McNamara Michael J. , Jia Xuefei , Sawalha Yazeed , Glass Katherine , Khorana Alok A. 
Published: February 2017

757 Background: Surgical resection of liver metastases provides a significant survival benefit, and potential for cure, in selected patients with metastatic colorectal cancer. There are very limited data on resection of lung metastases in patients with colorectal lung metastases. We evaluated outcomes after resection of lung metastases in patients with colorectal cancer. Methods: We conducted a retrospective cohort study in patients who underwent resection of pulmonary metastases between 2/2006 and 6/2013 at Cleveland Clinic. Clinical, pathologic, and outcome data were collected by electronic medical records review. Overall survival (OS) as the primary endpoint was summarized by Kaplan-Meier method and analyzed by log-rank tests. Results: The study population comprised 32 patients. Overall, 20 patients were male and median age at diagnosis of lung metastasis was 60.0 years (range 30.4-81.9). All patients had resection of primary tumor. Eleven patients had preoperative chemotherapy and 12 had adjuvant chemotherapy. Patients with unilateral metastases comprised the majority of patients (N = 22, 68.8%); 59% (N = 19) had a solitary metastasis. The median diameter of lung metastases was 20.5 mm (range 7.0 -50.0). Ten patients had concurrent liver metastases, eight of whom had liver resection as well. Overall, 31% (10/32) of patients recurred, with 50% (16/32) of recurrences in the lung, and 28% died. Estimated median OS was 55.0 months. Estimated 5-year OS was 32% ± 17%. Higher CEA level ( ≥ 4.5 ng/mL) at the time of diagnosis of lung metastasis was associated with worsened OS (p = 0.026). Other potential prognostic factors, such as laterality, number of lung metastases, and extrapulmonary lesions, were not associated with overall survival in this study population. Conclusions: Our study showed resection of lung metastases in select patients with colorectal cancer can be associated with prolonged survival in the range seen with resection of liver metastases. Higher CEA level at time of diagnosis of lung metastasis is associated with poorer prognosis. More data are necessary to identify approaches to patient selection in the metastatic colorectal setting.
The cancer vaccine therapy using DCs derived from iPS cells (iPSDCs) expressing TAA gene.
Authors: Iwamoto Hiromitsu , Ojima Toshiyasu , Kitadani Junya , Tabata Hiroaki , Hayata Keiji , Katsuda Masahiro , Miyazawa Motoki , Nakamura Masaki , Nakamori Mikihito , Yamaue Hiroki 
Published: February 2017

768 Background: Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the initiation of anti-tumor immune responses. Many cancer patients have previously been treated by the cancer vaccine therapy using DCs worldwide. We have employed a study of a cancer vaccine therapy using genetically modified DCs expressing tumor-associated antigen (TAA) gene. Clinically DCs are generated from the peripheral blood monocytes of patients. Thus the number of monocytes and potential of them are limited, so they are serious obstacle. Recent studies have revealed that induced pluripotent stem (iPS) cells can be generated from murine fibroblasts. Furthermore, it has been reported that DCs can be successfully derived from murine iPS cells (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of naive DCs, then the above-mentioned problems may be solved. Methods: We have induced iPSDCs from murine iPS cells by 4 steps and examined the efficacy as APCs of iPSDCs compared with naive DCs. We also examined whether a vaccine therapy using genetically modified iPSDCs can induce strong therapeutic antitumor immunity compared with naive DCs. Next, we examined the therapeutic antitumor immunity of iPSDCs expressing CEA gene compared with that of naive DCs in pre-clinical study with CEA transgenic mice. Results: We have clarified that genetically modified iPSDCs have an equal efficacy as APCs and TAA-specific therapeutic antitumor immunity, equivalent to naive DCs. And we also have clarified that genetically modified iPSDCs expressing CEA gene have a TAA-specific therapeutic antitumor immunity. Conclusions: This vaccine strategy using genetically modified iPSDCs has an equal capacity with naive DCs in terms of a therapeutic efficacy. Now, we are engaging another pre-clinical study with human, in an effort to apply in a clinical setting.
Adjuvant chemotherapy with or without concurrent radiotherapy in stage IB patients with gastric cancer: Subgroup analysis of the adjuvant chemoradiotherapy in stomach tumors (ARTIST) phase III trial.
Authors: Song Haa-na , Cho Jinhyun , Jung Ki Sun , Lee Su Jin , Kim Seung Tae , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki 
Published: February 2017

95 Background: To evaluate the risk of recurrence in patients with pathologically staged Ib, according to the American Joint Committee on Cancer (AJCC) 2002 staging system, gastric cancer (GC) in the phase III adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. Methods: Among 458 GC patients enrolled in ARTIST, 99 had stage Ib (T2N0 or T1N1) disease. Patients were randomly assigned to receive adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n = 50)) or chemoradiotherapy (XPRT, n = 49). Kaplan-Meier method was used to calculate disease-free survival (DFS). Cox proportional hazard models were employed to determine associations between the addition of radiotherapy to XP and DFS after adjustment for patient and disease characteristics. Additionally, analyses were performed according to the AJCC 2010 staging system. Results: With 7 years of follow-up, there were 18 recurrences. The 5-year DFS rates were 88% and 84% in XP and XPRT patients, respectively (P = 0.537). When we reviewed the pathologic stages of the patients according to the AJCC 2010 system, stage migration from Ib to II occurred in 71% of the patients: 98% of the T2N0 patients were reclassified as T3N0, and 42% of the T1N1 patients were reclassified as T1N2. The patients classified as stage Ib according to the AJCC 2002 system and reclassified as stage II exhibited worse, although statistically insignificant, prognosis than the patients who remained in stage Ib (5-year DFS 83% vs. 93%, P = 0.183, HR 1.178, 95% CI 0.420-3.311, P = 0.158). When we compared 5-year DFS in 70 stage II (AJCC 2010 system) patients, the addition of radiotherapy to XP chemotherapy resulted, although again statistically insignificant (P = 0.234), in worse outcome in XPRT arm (77%) than in XPRT arm (88%). Conclusions: This subgroup analysis confirms the clinical relevance of the AJCC 2010 staging system in GC. The role of adjuvant chemotherapy in stage II GC warrants further investigation.
A phase II trial to assess the activity and safety of the hypoxia-activated prodrug evofosfamide (TH-302) in combination with sunitinib in patients with disseminated grade 1 and 2 pancreatic neuroendocrine tumors (pNET) as a first-line approach: The GETNE-1408 trial.
Authors: Grande Enrique , Castellano Daniel E. , Custodio Ana B. , Garcia-Carbonero Rocio , González Encarnación , López-López Carlos , Munarriz Javier , Sevilla Isabel , Teule Alexandre , Benavent Viñuales Marta , Alonso Teresa , Gajate Borau Pablo , Palacios José , Capdevila Jaume 
Published: February 2017

TPS479 Background: Pancreatic-NETs are highly vascular tumors. The anti-angiogenetic sunitinib was approved in advanced pNETs based on prolongation of progression-free survival. Upregulation of several proangiogenic factors that reflects intratumor hypoxia conditions might drive resistance to sunitinib in pNETs. Evofosfamide is a prodrug that under hypoxic conditions preferentially releases a brominated version of isophosphoramide mustard and has shown activity in cell lines from neural crest derived tumors such as melanoma and glioblastoma/astrocytoma. We hypothesize that evofosfamide may have activity in the pathologic hypoxic conditions present in the tumor environment of neuroendocrine tumors inducing responses that may be consolidated and prolonged with sunitinib in patients with advanced pNETs that are naïve for systemic treatment. Methods: This is a prospective, non randomized, open-label, phase II study that is being conducted in 10 university sites belonging to the Spanish Task Force Group for NETs (GETNE) in Spain. Patients with histologically proven diagnosis of progressive unresectable or metastatic pNET with Ki67 < 20% and grade 1 or 2 will receive sunitinib orally at 37.5 mg PO daily on days 1 to 28 of a 28-day cycle (4 weeks) plus evofosfamide administered at 340 mg/m2 by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 28-day cycle (4 weeks). Hypoxia-related tumor markers, single nucleotide polymorphisms related to activity and metabolism of antiangiogenic agents (VEGFR2, VEGFR3, PDGFR-α, VEGF-A, IL8, CYP3A4, CYP3A5, ABCB1-2) will be correlated with clinical outcome. In this study it is planned to include 43 patientsbased on a two-stage Simon’s phase II design (α = 0.05, β = 80%). If the trial shows 8 responses or more among 43 patients, the treatment will be considered for further investigation. EudraCT number: 2014-004072-30 Clinical trial information: NCT02402062.