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Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
June 3, 2017: Oncotarget
Chiara Cremolini, Federica Marmorino, Fotios Loupakis, Gianluca Masi, Carlotta Antoniotti, Lisa Salvatore, Marta Schirripa, Luca Boni, Vittorina Zagonel, Sara Lonardi, Giuseppe Aprile, Emiliano Tamburini, Vincenzo Ricci, Monica Ronzoni, Filippo Pietrantonio, Chiara Valsuani, Gianluca Tomasello, Alessandro Passardi, Giacomo Allegrini, Samantha Di Donato, Daniele Santini, Alfredo Falcone
BACKGROUND: Chemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients. Different chemotherapy backbones may be chosen, including one to three drugs, based on patients' general conditions and comorbidities, treatments' objectives, and disease characteristics. TRIBE trial demonstrated a significant advantage in terms of progression-free survival and overall survival for FOLFOXIRI plus bevacizumab as compared with FOLFIRI plus bevacizumab...
June 9, 2017: BMC Cancer
Anita Micheel, Felix Aigner, Oliver Henke
Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression...
June 2017: Deutsche Medizinische Wochenschrift
Gianluca Tomasello, Fausto Petrelli, Michele Ghidini, Alessandro Russo, Rodolfo Passalacqua, Sandro Barni
Importance: The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. Objective: To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions...
July 13, 2017: JAMA Oncology
Y Song, W W Li, J Huang
Objective: To establish the maximum tolerated dose (MTD) of 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI), and to evaluate the safety and efficacy in Chinese patients with advanced colorectal cancer. Methods: Patients were treated with a regimen consisting of infusional 5-fluorouracil (2 400 mg/m(2) on day 1), leucovorin (200 mg/m(2) on day 1), oxaliplatin (85 mg/m(2) on day 1), and irinotecan (at doses from 150 to 180 mg/m(2) on day 8) according to the dose-escalation schema. Treatment was repeated every 14 days...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Mingyi Zhou, Ping Yu, Dengue Bilibili Hernick Davin, Yanrong Li, Yuanhe Wang, Lingyu Fu, Jingdong Zhang
Whether the intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment could improve the prognosis of metastatic colorectal cancer (mCRC) patients is controversial. PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews,, the databases of conferences were queried to identify RCTs evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of mCRC patients...
May 9, 2017: Oncotarget
Frederico Leal, Fernanda Proa Ferreira, Andre Deeke Sasse
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases...
March 24, 2017: Clinical Colorectal Cancer
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
Haitao Zhou, Yan Song, Jun Jiang, Haitao Niu, Hong Zhao, Jianwei Liang, Hao Su, Zheng Wang, Zhixiang Zhou, Jing Huang
OBJECTIVE: This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer. METHODS: Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2), combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m(2) by 44 h infusion or capecitabine 1 g/m(2) or S-1 40-60 mg b...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Takafumi Nishii, Yasutake Uchima, Yoshihito Yamakoshi, En Wang, Daisuke Nagashima, Toshiki Hirakawa, Naoki Aomatsu, Takehiko Iwauchi, Junya Morimoto, Kazunori Nakazawa, Seika Tei, Kazuhiro Takeuchi
We report 2 cases of metastatic rectal cancer patients who received chemotherapy with FOLFOXIRI plus bevacizumab(Bev). Case 1: A 54-year-old woman diagnosed with advanced rectal cancer with synchronous liver metastasis underwent a laparoscopic low anterior resection. After the operation, she received FOLFOXIRI plus Bev treatment, and experienced Grade 4 adverse events, including dyspnea and ventricular fibrillation(Vf). After chemotherapy, no other metastasis was detected except a liver metastasis, and partial resection of the liver was performed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Chiara Cremolini, Mariaelena Casagrande, Fotios Loupakis, Giuseppe Aprile, Francesca Bergamo, Gianluca Masi, Roberto Moretto R, Filippo Pietrantonio, Federica Marmorino, Gemma Zucchelli, Gianluca Tomasello, Giuseppe Tonini, Giacomo Allegrini, Cristina Granetto, Laura Ferrari, Lucio Urbani, Umberto Cillo, Pierluigi Pilati, Elisa Sensi, Alessio Pellegrinelli, Massimo Milione, Gabriella Fontanini, Alfredo Falcone
Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest...
March 2017: European Journal of Cancer
Wei Xu, Meng Kuang, Yang Gong, Chunxiang Cao, Jinfei Chen, Cuiju Tang
BACKGROUND: The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%-80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC...
2016: OncoTargets and Therapy
Jacopo Giuliani, Andrea Bonetti
In light of the relevant expenses of pharmacologic interventions, it might be interesting to make a balance between the cost of the new drugs administered and the difference in progression-free survival in first-line treatments for advanced colorectal cancer. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival for each trial. The costs are from the pharmacy of our hospital in Legnago, Italy. We evaluated 28 phase III randomized controlled trials that included 19,958 patients...
December 2016: Clinical Colorectal Cancer
S Matsusaka, S Cao, D L Hanna, Y Sunakawa, M Ueno, N Mizunuma, W Zhang, D Yang, Y Ning, S Stintzing, A Sebio, S Stremitzer, S Yamauchi, A Parekh, S Okazaki, M D Berger, R El-Khoueiry, A Mendez, W Ichikawa, F Loupakis, H-J Lenz
We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing...
August 9, 2016: Pharmacogenomics Journal
Mashaal Dhir, Deepa Magge, Stephanie Novak, David L Bartlett, Amer H Zureikat
BACKGROUND: Hepatic artery infusion (HAI) chemotherapy is an effective regional therapy for unresectable colorectal liver metastases (U-CRLM).1 (,) 2 One of its limitations is the need for a laparotomy, which can delay the use of systemic therapy.3 Here, we describe a purely robotic technique for placement of an HAI pump (Fig 1). PATIENT: A 62-year-old male presented with a symptomatic ascending colon cancer and multiple bilobar unresectable liver metastases. He underwent laparoscopic right colectomy followed by six cycles of FOLFOXIRI and bevacizumab with stable disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and also underwent robotic HAI pump placement...
December 2016: Annals of Surgical Oncology
Caterina Vivaldi, Chiara Caparello, Gianna Musettini, Giulia Pasquini, Silvia Catanese, Lorenzo Fornaro, Monica Lencioni, Alfredo Falcone, Enrico Vasile
FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty-seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
Y Sunakawa, T Bekaii-Saab, S Stintzing
Colorectal cancer is one of the most frequent solid tumors in the western world, with low survival rates in patients with metastatic disease. Doublet chemotherapy regimens such as FOLFOX or FOLFIRI are the mainstay of standard first-line chemotherapy in the metastatic setting. The conventional treatment as a first-line approach is continuous application until progression or intolerable toxicities. However, only one third of patients are treated until progression mainly due to the side effects of chemotherapy...
April 2016: Cancer Treatment Reviews
Johanna C Bendell, Ahmed Zakari, James D Peyton, Ralph Boccia, Mark Moskowitz, Victor Gian, Andrew Lipman, David Waterhouse, Richard LoCicero, Chris Earwood, Cassie M Lane, Anthony Meluch
BACKGROUND: Patients with liver-only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first-line treatment for KRAS wild-type mCRC with liver-only metastasis. METHODS: Patients received FOLFOXIRI (5-FU, 3,200 mg/m(2), 48-hour continuous intravenous (i...
March 2016: Oncologist
C Cremolini, F Loupakis, G Masi, S Lonardi, C Granetto, M L Mancini, S Chiara, R Moretto, D Rossini, S Vitello, G Allegrini, G Tonini, F Bergamo, G Tomasello, M Ronzoni, A Buonadonna, S Bustreo, C Barbara, L Boni, A Falcone
BACKGROUND: FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. PATIENTS AND METHODS: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group)...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Yu Sunakawa, Marta Schirripa, Heinz-Josef Lenz
The management of metastatic colorectal cancer substantially improved over the last 10 years and median overall survival of patients might exceed 30 months. The selection of an effective first-line treatment represents a crucial point in order to achieve good outcome results. In the last years, the intensive FOLFOXIRI regimen in combination with bevacizumab became a new standard option in this setting. In the present review we summarized the main steps of FOLFOXIRI regimen development from the first pilot study to the recent findings with biological agents, with a specific focus on practical aspects, such as patient's selection, adverse event management, treatment schedules and post-progression strategies...
April 2016: Critical Reviews in Oncology/hematology
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