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Alectinib

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https://www.readbyqxmd.com/read/29027209/heterogeneous-distribution-of-alectinib-in-neuroblastoma-xenografts-revealed-by-matrix-assisted-laser-desorption-ionisation-mass-spectrometry-imaging-a-pilot-study
#1
Shoraku Ryu, Mitsuhiro Hayashi, Hiroaki Aikawa, Isamu Okamoto, Yasuhiro Fujiwara, Akinobu Hamada
BACKGROUND AND PURPOSE: The penetration of the anaplastic lymphoma kinase (ALK) inhibitor alectinib in neuroblastomas and the relationship between alectinib and ALK expression are unknown. The aim of this study was to perform a quantitative investigation of the inter- and intra-tumoural distribution of alectinib in different neuroblastoma xenograft models using matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). EXPERIMENTAL APPROACH: The distribution of alectinib in NB1 (ALK amplification) and SK-N-FI (ALK wild-type) xenograft tissues was analysed using MALDI-MSI...
October 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29021430/crizotinib-induced-rectal-perforation-with-abscess
#2
Asako Yanagisawa, Noriko Hayama, Hiroyuki Amano, Makoto Nakamura, Satoshi Hirano, Sukeyuki Nakamura, Hiroshi Tabeta
An 86-year-old Japanese man was diagnosed with stage IV lung adenocarcinoma. The patient was treated with crizotinib after EML4-ALK rearrangement was detected from his pleural effusion. He subsequently developed abdominal pain and rebound tenderness in the right lower abdomen. Contrast-enhanced abdominal CT showed a low-density area in the abdominal cavity. The size of the abscess was decreased by drainage and the administration of antibiotics. Fistulography revealed a fistula from the rectum to the abscess, and a diagnosis of lower intestinal tract perforation with abscess formation was made...
October 11, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28979145/anaplastic-lymphoma-kinase-inhibition-in-metastatic-non-small-cell-lung-cancer-clinical-impact-of-alectinib
#3
REVIEW
Ittai B Muller, Adrianus J de Langen, Elisa Giovannetti, Godefridus J Peters
A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28977547/dramatic-response-to-alectinib-in-inflammatory-myofibroblastic-tumor-with-anaplastic-lymphoma-kinase-fusion-gene
#4
Masafumi Saiki, Fumiyoshi Ohyanagi, Ryo Ariyasu, Junji Koyama, Tomoaki Sonoda, Shingo Nishikawa, Satoru Kitazono, Noriko Yanagitani, Atsushi Horiike, Hironori Ninomiya, Yuichi Ishikawa, Makoto Nishio
Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors...
September 18, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28955006/phase-i-ii-study-of-alectinib-in-lung-cancer-with-ret-fusion-gene-study-protocol
#5
Shinji Takeuchi, Toshinori Murayama, Kenichi Yoshimura, Takahiro Kawakami, Shizuko Takahara, Yasuhito Imai, Yoshikazu Kuribayashi, Katsuhiko Nagase, Koichi Goto, Makoto Nishio, Yoshinori Hasegawa, Miyako Satouchi, Katsuyuki Kiura, Takashi Seto, Seiji Yano
BACKGROUND: The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC. METHODS/DESIGN: RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28955002/the-case-of-double-primary-lung-adenocarcinomas-with-an-egfr-mutation-and-alk-translocation-successfully-treated-with-alectinib-at-the-post-surgical-recurrence
#6
Yoshio Tsunezuka, Nobuyoshi Tanaka, Hideki Fujimori, Yuki Togashi, Satoko Baba, Kengo Takeuchi, Kazuyoshi Katayanagi, Hiroshi Kurumaya, Hironori Kitade, Shinji Atagi, Seiji Yano
A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28932515/the-j-alex-trial-is-frontline-alectinib-a-new-standard-of-care
#7
EDITORIAL
Jeffrey Zweig, Heather A Wakelee
No abstract text is available yet for this article.
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28878445/phase-ii-trial-of-ch5424802-alectinib-hydrochloride-for-recurrent-or-refractory-alk-positive-anaplastic-large-cell-lymphoma-study-protocol-for-a-non-randomized-non-controlled-trial
#8
Hirokazu Nagai, Reiji Fukano, Masahiro Sekimizu, Akiko Kada, Akiko M Saito, Ryuta Asada, Tetsuya Mori
Currently, a standard therapy has not been established for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. While there are many treatment options, such as hematopoietic stem cell transplantation, patients with resistant disease to conventional chemotherapies have particularly poor prognosis. There is urgent need to develop new drugs because of the lack of a standard therapy and poor prognoses. This phase II trial is designed for evaluating the efficacy and safety of alectinib hydrochloride for patients with recurrent or refractory anaplastic lymphoma kinase -positive anaplastic large cell lymphoma...
August 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28856564/the-current-landscape-of-anaplastic-lymphoma-kinase-alk-in-non-small-cell-lung-cancer-emerging-treatment-paradigms-and-future-directions
#9
Angel Qin, Shirish Gadgeel
Tumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3-7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of more potent next-generation ALK inhibitors...
August 31, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28794371/successful-treatment-with-alectinib-for-choroidal-metastasis-in-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer
#10
Tomoko Funazo, Kyohei Morita, Naoya Ikegami, Chisato Konishi, Satoshi Nakao, Ryo Ariyasu, Masato Taki, Kazuhiko Nakagawa, Moon Hee Hwang, Chie Yoshimura, Toshiaki Wakayama, Yasuo Nishizaka
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy...
September 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28794366/regression-of-crizotinib-associated-complex-cystic-lesions-after-switching-to-alectinib
#11
Kageaki Taima, Hisashi Tanaka, Yoshihito Tanaka, Masamichi Itoga, Shingo Takanashi, Sadatomo Tasaka
Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation...
September 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28725874/metabolites-of-alectinib-in-human-their-identification-and-pharmacological-activity
#12
Mika Sato-Nakai, Kosuke Kawashima, Toshito Nakagawa, Yukako Tachibana, Miyuki Yoshida, Kenji Takanashi, Peter N Morcos, Martin Binder, David J Moore, Li Yu
Two metabolites (M4 and M1b) in plasma and four metabolites (M4, M6, M1a and M1b) in faeces were detected through the human ADME study following a single oral administration of [(14)C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28721071/adverse-renal-effects-of-anaplastic-lymphoma-kinase-inhibitors-and-the-response-to-alectinib-of-an-alk-lung-cancer-patient-with-renal-dysfunction
#13
Midori Shimada, Minoru Fukuda, Masaaki Fukuda, Takeshi Kitazaki, Kohji Hashiguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuto Ashizawa, Hiroshi Mukae
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28689043/pooled-systemic-efficacy-and-safety-data-from-the-pivotal-phase-ii-studies-np28673-and-np28761-of-alectinib-in-alk-positive-non-small-cell-lung-cancer
#14
James Chih-Hsin Yang, Sai-Hong Ignatius Ou, Luigi De Petris, Shirish Gadgeel, Leena Gandhi, Dong-Wan Kim, Fabrice Barlesi, Ramaswamy Govindan, Anne-Marie C Dingemans, Lucio Crino, Herve Lena, Sanjay Popat, Jin Seok Ahn, Eric Dansin, Sophie Golding, Walter Bordogna, Bogdana Balas, Peter N Morcos, Ali Zeaiter, Alice T Shaw
INTRODUCTION: Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. METHODS: Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily...
July 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28683775/alk-rearranged-lung-squamous-cell-carcinoma-responding-to-alectinib-a-case-report-and-review-of-the-literature
#15
Nobuaki Mamesaya, Kazuhisa Nakashima, Tateaki Naito, Takashi Nakajima, Masahiro Endo, Toshiaki Takahashi
BACKGROUND: Although anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown...
July 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28676215/identification-of-a-novel-t1151k-alk-mutation-in-a-patient-with-alk-rearranged-nsclc-with-prior-exposure-to-crizotinib-and-ceritinib
#16
Viola W Zhu, J Jean Cui, Maria Fernandez-Rocha, Alexa B Schrock, Siraj M Ali, Sai-Hong Ignatius Ou
Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) derive significant clinic benefit from treatment with ALK inhibitors. Crizotinib was the first approved tyrosine kinase inhibitor (TKI) for this distinct molecular subset of NSCLC. Disease progression on TKI inevitably arises secondary to diverse resistance mechanisms among which emergence of secondary ALK mutations is one of many ways in which tumor cells have adapted to survive. Therefore there is a clinical imperative to identify acquired ALK mutations via repeat tissue biopsy if clinically feasible...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28657423/in-vitro-metabolism-of-alectinib-a-novel-potent-alk-inhibitor-in-human-contribution-of-cyp3a-enzymes
#17
Toshito Nakagawa, Stephen Fowler, Kenji Takanashi, Kuresh Youdim, Tsuyoshi Yamauchi, Kosuke Kawashima, Mika Sato-Nakai, Li Yu, Masaki Ishigai
1. The in vitro metabolism of alectinib, a potent and highly selective oral anaplastic lymphoma kinase inhibitor, was investigated. 2. The main metabolite (M4) in primary human hepatocytes was identified, which is produced by deethylation at the morpholine ring. Three minor metabolites (M6, M1a, and M1b) were also identified, and a minor peak of hydroxylated alectinib (M5) was detected as a possible precursor of M4, M1a, and M1b. 3. M4, an important active major metabolite, was produced and further metabolized to M6 by CYP3A, indicating that CYP3A enzymes were the principal contributors to this route...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#18
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28625556/alectinib-surpasses-crizotinib-for-untreated-alk-positive-nsclc
#19
Judith A Gilbert
No abstract text is available yet for this article.
June 15, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28606126/pooled-safety-analyses-of-alk-tki-inhibitor-in-alk-positive-nsclc
#20
Qian Zhu, Hao Hu, De-Sheng Weng, Xiao-Fei Zhang, Chang-Long Chen, Zi-Qi Zhou, Yan Tang, Jian-Chuan Xia
BACKGROUND: The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear. METHODS: We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials...
June 12, 2017: BMC Cancer
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