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Cancer Chemotherapy and Pharmacology

Michael A Badruddoja, Marjorie Pazzi, Abhay Sanan, Kurt Schroeder, Kevin Kuzma, Thomas Norton, Thomas Scully, Daruka Mahadevan, Michael Malek Ahmadi
PURPOSE: Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblastoma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efficacy in adult patients with recurrent glioblastoma...
August 14, 2017: Cancer Chemotherapy and Pharmacology
Nobuaki Matsubara, Hirofumi Mukai, Ako Hosono, Mai Onomura, Masaoki Sasaki, Yoko Yajima, Kensei Hashizume, Masanobu Yasuda, Miho Uemura, Christian Zurth
PURPOSE: This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this open-label, nonrandomized, two-cohort, dose-escalating phase 1 study, Japanese patients with mCRPC were enrolled after a screening period. In the single-dose period (≈1 week), darolutamide was administered at 300 mg (Cohort 1) or 600 mg (Cohort 2) on day-5 (fasting state) and day-2 (fed condition)...
August 11, 2017: Cancer Chemotherapy and Pharmacology
N Blank, I Laskov, R Kessous, L Kogan, S Lau, I A Sebag, Walter H Gotlieb, L Rudski
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]...
August 11, 2017: Cancer Chemotherapy and Pharmacology
Shareni Jeyamogan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need for newer and more powerful anti-tumor agents. The search for new anti-tumor compounds originating from natural resources is a promising research area. Animals living in polluted environments are a potent source of anti-tumor agents. Under polluted milieus, species such as crocodiles, feed on rotten meat, are exposed to heavy metals, endure high levels of radiation, and are among the very few species to survive the catastrophic Cretaceous-Tertiary extinction event with a prolonged lifespan...
August 9, 2017: Cancer Chemotherapy and Pharmacology
Zhengqiu Zhou, Tracy A Howard, John L Villano
Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day...
August 8, 2017: Cancer Chemotherapy and Pharmacology
Mohamed M Abdel-Daim, Omnia E Kilany, Hesham A Khalifa, Amal A M Ahmed
PURPOSE: Doxorubicin (DOX) is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of allicin, a dietary garlic active constituent against DOX-induced cardiotoxicity. METHODS: Forty male Swiss albino mice were divided into five groups, which received normal saline, oral allicin (20 mg kg(-1) once daily), intraperitoneal DOX (on the 7, 9 and 11th day of the experiment), or DOX plus once daily allicin at 10 or 20 mg kg(-1)...
August 7, 2017: Cancer Chemotherapy and Pharmacology
Munetaka Takekuma, Keita Mori, Tetsuji Iida, Kazuko Kurihara, Motoaki Saitou, Hideki Tokunaga, Kei Kawana, Masae Ikeda, Toyomi Satoh, Toshiaki Saito, Etsuko Miyagi, Yutaka Nagai, Akiko Furusawa, Yoshiaki Kawano, Kouichiro Kawano, Tsutomu Tabata, Yukinobu Ota, Ryoji Hayase, Mikio Mikami, Toru Sugiyama
PURPOSE: This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer. METHODS: The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed. RESULTS: A total of 677 patients from 71 medical centers were analyzed...
August 7, 2017: Cancer Chemotherapy and Pharmacology
Jung Han Kim, Bum Jun Kim, Hyun Joo Jang, Hyeong Su Kim
PURPOSE: The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria. METHODS: Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria. RESULTS: A total of 181 patients were recruited from the seven studies...
August 5, 2017: Cancer Chemotherapy and Pharmacology
Melissa E Badowski
PURPOSE: Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV...
August 5, 2017: Cancer Chemotherapy and Pharmacology
Laurent Laborde, Fatos Oz, Mitko Ristov, Daniel Guthy, Dario Sterker, Paul McSheehy
PURPOSE: Everolimus is a drug used successfully in a number of different oncology indications, but significant on-target toxicities exist. We explored the possibility of improving the therapeutic index (TI) by studying alternative means of administering the drug based upon low continuous dosing. METHODS: All studies were performed using naïve nude mice or nude mice bearing s.c. human renal 786-O tumours or human breast MDA-MB-468 tumours. Everolimus was administered via a standard emulsion, either i...
August 4, 2017: Cancer Chemotherapy and Pharmacology
Qiong Yang, Florian Puhm, Michael Freissmuth, Christian Nanoff
PURPOSE: Small-molecule inhibitors of heat-shock protein 90 (HSP90) have been under development as chemotherapeutic agents. The adverse events reported from early clinical trials included hyponatremia. Given the limited number of patients enrolled, the number of hyponatremia incidents was remarkable and repeatedly, the event was judged as severe. Inappropriate V2 vasopressin receptor stimulation is an established cause of hyponatremia. We explored the hypothesis that HSP90 inhibition produces hypersensitivity to vasopressin by upregulating V2-receptors...
August 4, 2017: Cancer Chemotherapy and Pharmacology
Shengshi Huang, Di Wang, Shu Zhang, Xiaoyan Huang, Dandan Wang, Muhammad Ijaz, Yikang Shi
PURPOSE: Paclitaxel has been reported to upregulate both AKT and MAPK signaling pathways and thereby compromises its antitumor efficacy. However, tunicamycin has the ability to downregulate AKT and MAPK pathways. The aim of the study is to investigate the antitumor activity of the combination treatment of paclitaxel with tunicamycin and the mechanisms involving the changes of antitumor efficacy. METHODS: Sulforhodamine B (SRB) assay was used to examine the cell viability upon treatment of breast cancer cells with paclitaxel, tunicamycin and the combination of both...
August 4, 2017: Cancer Chemotherapy and Pharmacology
Tamás Solymosi, Zsolt Ötvös, Réka Angi, Betti Ordasi, Tamás Jordán, László Molnár, John McDermott, Vanessa Zann, Ann Church, Stuart Mair, Genovéva Filipcsei, Gábor Heltovics, Hristos Glavinas
PURPOSE: Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers...
August 3, 2017: Cancer Chemotherapy and Pharmacology
Ronald Stoller, John C Schmitz, Fei Ding, Shannon Puhalla, Chandra P Belani, Leonard Appleman, Yan Lin, Yixing Jiang, Salah Almokadem, Daniel Petro, Julianne Holleran, Brian F Kiesel, R Ken Czambel, Benedito A Carneiro, Emmanuel Kontopodis, Pamela A Hershberger, Madani Rachid, Alice Chen, Edward Chu, Jan H Beumer
BACKGROUND: Veliparib (ABT-888) is an oral PARP inhibitor expected to increase gemcitabine activity. This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine. METHODS: Patients with advanced solid tumors received veliparib (10-40-mg PO BID) on chemotherapy weeks with gemcitabine 500-750-mg/m(2) IV on days 1, 8, and 15 (28-day cycle), or on days 1 and 8 (21-day cycle)...
August 2, 2017: Cancer Chemotherapy and Pharmacology
Sergey S Gordeyev, Arsen O Rasulov, Vera A Gorbounova, Sergey I Tkachev, Valeriya V Glebovskaya, Mikhail Yu Fedyanin, Nataliya S Besova, Yulia E Surayeva
PURPOSE: The goals of this study were to assess safety and efficacy of triplet chemoradiotherapy (CRT) with paclitaxel for squamous cell anal carcinoma (SCAC). METHODS: Patients with stage I-IIIB SCAC were enrolled and received 52-58 Gy intensity-modulated radiotherapy (IMRT) (with dose based on the T stage) in consecutive daily 1.8-2.2 Gy fractions. The concurrent chemotherapy consisted of paclitaxel 45 mg/m(2) days 3, 10, 17, 24, 31, capecitabine 625 mg/m(2) bid on treatment days and mitomycin C 10 g/m(2) on day 1...
August 1, 2017: Cancer Chemotherapy and Pharmacology
Hisao Imai, Tomohide Sugiyama, Tomohiro Tamura, Hiroyuki Minemura, Kyoichi Kaira, Kenya Kanazawa, Hiroshi Yokouchi, Takashi Kasai, Takayuki Kaburagi, Koichi Minato
PURPOSE: Amrubicin is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). Previous studies reported its effectiveness and severe hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly patients with SCLC has not been described. The objective of this study was to investigate the feasibility of amrubicin monotherapy in elderly patients and its efficacy for relapsed SCLC. METHODS: A retrospective cohort study design was used...
July 31, 2017: Cancer Chemotherapy and Pharmacology
Hirotsugu Kenmotsu, Yasuhisa Ohde, Kazushige Wakuda, Kazuhisa Nakashima, Shota Omori, Akira Ono, Tateaki Naito, Haruyasu Murakami, Hideaki Kojima, Shoji Takahashi, Mitsuhiro Isaka, Masahiro Endo, Toshiaki Takahashi
PURPOSE: Despite the efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy for patients who have undergone surgical resection of non-small cell lung cancer (NSCLC), few reports have presented survival data for Asian patients treated with adjuvant chemotherapy involving a combination of CDDP and vinorelbine (VNR). This study was performed to evaluate the survival of patients with NSCLC who received postoperative adjuvant chemotherapy comprising CDDP + VNR. METHODS: We retrospectively evaluated patients with NSCLC who received adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between February 2006 and October 2011...
July 31, 2017: Cancer Chemotherapy and Pharmacology
Gayathri Srinivasan, Gurjit Singh Sidhu, Elizabeth A Williamson, Aruna S Jaiswal, Nasreen Najmunnisa, Keith Wilcoxen, Dennie Jones, Thomas J George, Robert Hromas
Malignant pleural mesotheliomas (MPM) are most often surgically unresectable, and they respond poorly to current chemotherapy and radiation therapy. Between 23 and 64% of malignant pleural mesothelioma have somatic inactivating mutations in the BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for survival, similar to the BRCA1/2 mutant breast and ovarian cancers...
July 29, 2017: Cancer Chemotherapy and Pharmacology
Xin-Min Zhao, Jing Zhao, Xiang-Hua Wu, Zhi-Guo Luo, Hui-Jie Wang, Hui Yu, Jian-Hua Chang, Jia-Lei Wang
BACKGROUND: Pemetrexed is the preferred chemotherapy agent in the management of non-squamous non-small cell lung cancer (non-sq-NSCLC), but lacks biomarkers predicting its efficacy. Dexamethasone, one of the premedications of pemetrexed, may downregulate p53 through the glucocorticoid receptor (GR). The purpose of our study was to explore the effect of GR in peripheral blood mononuclear cells (PBMC) and its role in predicting pemetrexed efficacy. METHODS: In all, 122 patients with stage IV non-sq-NSCLC who received first-line pemetrexed-containing chemotherapy were retrospectively reviewed...
July 28, 2017: Cancer Chemotherapy and Pharmacology
Allen Lee Cohn, Takayuki Yoshino, Volker Heinemann, Radka Obermannova, György Bodoky, Jana Prausová, Rocio Garcia-Carbonero, Tudor Ciuleanu, Pilar Garcia-Alfonso, David C Portnoy, Eric Van Cutsem, Kentaro Yamazaki, Philip R Clingan, Jonathon Polikoff, Sara Lonardi, Lisa M O'Brien, Ling Gao, Ling Yang, David Ferry, Federico Nasroulah, Josep Tabernero
PURPOSE: To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. METHODS: Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C min,ss) and survival...
July 25, 2017: Cancer Chemotherapy and Pharmacology
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