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Oral Irinotecan

Xiaofei Zhu, Xiaoping Ju, Fei Cao, Fang Fang, Shuiwang Qing, Yuxin Shen, Zhen Jia, Yangsen Cao, Huojun Zhang
INTRODUCTION: Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine...
December 1, 2016: BMJ Open
Godefridus J Peters, K Smid, E Meijer, C J van Groeningen, L G Leon
5-Fluorouracil (5FU) is still a major drug in combinations regimens for the treatment of colorectal cancer (CRC) both in the adjuvant and palliative setting. 5FU or its oral prodrug capecitabine is usually combined with irinotecan/oxaliplatin and the novel agents bevacizumab/cetuximab. Although this improved the outcome, the overall prognosis in patients with metastasized disease is still relatively poor. Although the target for 5FU, thymidylate synthase was shown to have a predictive value, this could only predict response in a subset of patients...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
Takashi Nishimura, Satoru Iwasa, Kengo Nagashima, Natsuko Okita, Atsuo Takashima, Yoshitaka Honma, Ken Kato, Tetsuya Hamaguchi, Yasuhide Yamada, Yasuhiro Shimada, Narikazu Boku
BACKGROUND: Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan. METHODS: A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes...
November 17, 2016: Gastric Cancer
Tomohiro Terada
 After the year 2000, the treatment of cancer remarkably changed, including the development of outpatient cancer chemotherapy. Meanwhile, we have encountered many clinical problems related to cancer patient pharmacy services. To resolve these problems, I have tried to establish the individualized and optimal cancer pharmacotherapy utilizing the findings of basic research. In this review, three topics of my research will be introduced. 1) In 2005, information regarding the genetic polymorphism of UGT1A1*28 was described in the package insert of the drug irinotecan in the United States...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Seiji Mabuchi, Eriko Yokoi, Takao Owa, Katsumi Kozasa, Michiko Yamashita, Eiji Kobayashi, Takuji Tomimatsu, Takeshi Yoki, Tateki Tsutui, Tadashi Kimura
OBJECTIVES: This study aimed to determine the maximum tolerated dose and acute dose-limiting toxicities (DLTs) of intravenous irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer. METHODS: Irinotecan was administered intravenously over the course of 90 minutes on day 1, and S-1 was given orally in 2 divided doses from days 1 to 14 of a 21-day cycle. The dose of S-1 was escalated in a stepwise fashion from 40 (level 1) to 60 mg/m (level 2) and then 80 mg/m (level 3), whereas the dosage of irinotecan remained the same (150 mg/m)...
September 2016: International Journal of Gynecological Cancer
Boram Han, Joo Young Jung, Hyeong Su Kim, Ji Woong Cho, Kab Choong Kim, Hyun Lim, Ho Suk Kang, Hong Il Ha, Min-Jeong Kim, Jung Hoon Kim, Dae Ro Choi, Geundoo Jang, Jung Han Kim, Hunho Song, Dae Young Zang
PURPOSES: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer. METHODS: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m(2); level 2, 85/120/80 mg/m(2); level 3, 85/120/100 mg/m(2); level 4, 85/150/100 mg/m(2); and level 5, 85/180/100 mg/m(2)...
September 15, 2016: Cancer Chemotherapy and Pharmacology
Richard A Forsgård, Riitta Korpela, Reetta Holma, Jere Lindén, Rafael Frias, Thomas Spillmann, Pia Österlund
PURPOSE: Gastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced gastrointestinal toxicity. METHODS: Male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg) or irinotecan (200 mg/kg)...
October 2016: Cancer Chemotherapy and Pharmacology
Xingdong Wang, Zhi Rao, Hongyan Qin, Guoqiang Zhang, Yanrong Ma, Yongwen Jin, Miao Han, Axi Shi, Yanping Wang, Xinan Wu
The usage of irinotecan hydrochloride (CPT-11) chemotherapy is hindered by its dose-limiting diarrhea which appears to be associated with the intestinal exposure to SN-38, the active metabolite of CPT-11. Hesperidin, a safe and natural food ingredient flavonoid, exhibits various biological properties. Accumulated evidence showed that the regulatory effect of hesperidin on the expression of Mrp2 in the liver may be one of the critical factors controlling the biliary excretion of SN-38. This study examined the effect of hesperidin on the pharmacokinetics of CPT-11 and SN-38 as well as the regulatory effect on the hepatic expression of Mrp2...
October 2016: Biopharmaceutics & Drug Disposition
Takao Takahashi, Yasunori Emi, Eiji Oki, Kazuma Kobayashi, Akihito Tsuji, Mototsugu Shimokawa, Takaho Tanaka, Yoshito Akagi, Yutaka Ogata, Hideo Baba, Kazuhiro Yoshida, Shoji Natsugoe, Yoshihiko Maehara
PURPOSE: Anti-epidermal growth factor receptor antibody therapy alone or in combination with irinotecan is recognized as a standard third-line treatment for KRAS wild-type unresectable metastatic colorectal cancer. However, in some cases, it is difficult to administer irinotecan after third-line treatment. Therefore, we examined the efficacy and safety of the combination of cetuximab and S-1 in patients with KRAS wild-type unresectable metastatic colorectal cancer who were previously treated with irinotecan, oxaliplatin, and fluoropyrimidines...
September 2016: Cancer Chemotherapy and Pharmacology
James M Cleary, Harvey J Mamon, Jackie Szymonifka, Raphael Bueno, Noah Choi, Dean M Donahue, Panos M Fidias, Henning A Gaissert, Michael T Jaklitsch, Matthew H Kulke, Thomas P Lynch, Steven J Mentzer, Jeffrey A Meyerhardt, Richard S Swanson, John Wain, Charles S Fuchs, Peter C Enzinger
BACKGROUND: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation...
July 13, 2016: BMC Cancer
Jianhong Peng, Zhizhong Pan
Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen...
June 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Toshi Takaoka, Tetsuo Kimura, Rai Shimoyama, Shunji Kawamoto, Kazuki Sakamoto, Fuminori Goda, Hiroshi Miyamoto, Yuji Negoro, Akihito Tsuji, Koji Yoshizaki, Takahiro Goji, Shinji Kitamura, Hiromi Yano, Koichi Okamoto, Masako Kimura, Toshiya Okahisa, Naoki Muguruma, Yoshiro Niitsu, Tetsuji Takayama
BACKGROUND: Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. METHODS: Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years...
August 2016: Cancer Chemotherapy and Pharmacology
Tomohiro Nishi, Yasuo Hamamoto, Michitaka Nagase, Tadamichi Denda, Kensei Yamaguchi, Kenji Amagai, Yoshinori Miyata, Yasuhiro Yamanaka, Kai Yanai, Tsutomu Ishikawa, Yoshifumi Kuroki, Hirofumi Fujii
Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100-180 mg/m(2) every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose...
June 2016: Oncology Letters
Matthew H G Katz, Qian Shi, Syed A Ahmad, Joseph M Herman, Robert de W Marsh, Eric Collisson, Lawrence Schwartz, Wendy Frankel, Robert Martin, William Conway, Mark Truty, Hedy Kindler, Andrew M Lowy, Tanios Bekaii-Saab, Philip Philip, Mark Talamonti, Dana Cardin, Noelle LoConte, Perry Shen, John P Hoffman, Alan P Venook
IMPORTANCE: Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE: To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting...
August 17, 2016: JAMA Surgery
Vanessa C Miranda, Maria Ignez Braghiroli, Luiza Dib Faria, Giovanni Bariani, Alexandra Alex, João Evangelista Bezerra Neto, Fernanda C Capareli, Jorge Sabbaga, Juliana Ferreira Lobo Dos Santos, Paulo M Hoff, Rachel P Riechelmann
BACKGROUND: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials. PATIENTS AND METHODS: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an anti-epidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m(2) and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent...
December 2016: Clinical Colorectal Cancer
Sébastien L Degorce, Bernard Barlaam, Elaine Cadogan, Allan Dishington, Richard Ducray, Steven C Glossop, Lorraine A Hassall, Franck Lach, Alan Lau, Thomas M McGuire, Thorsten Nowak, Gilles Ouvry, Kurt G Pike, Andrew G Thomason
A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration...
July 14, 2016: Journal of Medicinal Chemistry
Motoki Yoshida, Akinori Takagane, Yasuhiro Miyake, Ken Shimada, Naoki Nagata, Atsushi Sato, Yutaka Ogata, Mutsumi Fukunaga, Koki Otsuka, Takao Takahashi, Hidetomo Matsumoto, Tatsuo Kagimura, Akihito Tsuji
OBJECTIVE: No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC. METHODS: Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle...
2016: Oncology
Stine Braendegaard Winther, Kanita Zubcevic, Camilla Qvortrup, Lene Weber Vestermark, Helle Anita Jensen, Merete Krogh, Halfdan Sorbye, Per Pfeiffer
BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients...
July 2016: Acta Oncologica
Itamar González-Perera, Fernando Gutiérrez-Nicolás, Gloria J Nazco-Casariego, Ruth Ramos-Díaz, Raquel Hernández-San Gil, José A Pérez-Pérez, Jonathan González García, Guillermo A González De La Fuente
Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase...
April 27, 2016: Journal of Oncology Pharmacy Practice
Daniel W Bowles, Mark Kochenderfer, Allen Cohn, Lucas Sideris, Nghia Nguyen, Vivian Cline-Burkhardt, Ian Schnadig, Minsig Choi, Lisle Nabell, Arvind Chaudhry, Robert Ruxer, Antonio Ucar, Diana Hausman, Luke Walker, Alexander Spira, Antonio Jimeno
BACKGROUND: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase/mammalian target of rapamycin signaling pathway is frequently altered in colorectal cancer (CRC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. This randomized phase II study evaluated cetuximab with or without PX-866 in patients with metastatic, anti-epidermal growth factor receptor-naive, KRAS codon 12 and 13 wild-type CRC. PATIENTS AND METHODS: Patients with metastatic CRC who had received both oxaliplatin and irinotecan were randomized (1:1) to cetuximab (400 mg/m(2) loading then 250 mg/m(2) weekly) with or without PX-866 (8 mg orally daily; arms A and B, respectively)...
March 31, 2016: Clinical Colorectal Cancer
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