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Venessa Chin, Adnan Nagrial, Katrin Sjoquist, Chelsie A O'Connor, Lorraine Chantrill, Andrew V Biankin, Rob Jpm Scholten, Desmond Yip
BACKGROUND: Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease. OBJECTIVES: To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer...
March 20, 2018: Cochrane Database of Systematic Reviews
Hidehiro Tajima, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Yoshinao Ohbatake, Koichi Okamoto, Shinichi Nakanuma, Shiro Terai, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Masafumi Inokuchi, Tomoharu Miyashita, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Tetsuo Ohta
The prognosis of patients with unresectable or recurrent pancreatic cancers is very poor. Prior to development of nab-paclitaxel (PTX) plus gemcitabine (GEM) therapy and FOLFIRINOX therapy, there was no recommended third-line chemotherapy after 5-fluorouracil (5-FU) and GEM-based regimens. The present study conducted a Phase I clinical trial of weekly low-dose PTX as a third-line palliative chemotherapy for patients with pancreatic cancer. PTX was administered on days 1, 8, 15, and 22 of each cycle, repeated twice as follows: Level 1, 40 mg/m2 (n=6); Level 2, 50 mg/m2 (n=4)...
April 2018: Molecular and Clinical Oncology
Adam J Camblin, Emily A Pace, Sharlene Adams, Michael D Curley, Victoria Rimkunas, Lin Nie, Gege Tan, Troy Bloom, Sergio Iadevaia, Jason Baum, Charlene Minx, Akos Czibere, Chrystal U Louis, Daryl C Drummond, Ulrik B Nielsen, Birgit Schoeberl, J Marc Pipas, Robert M Straubinger, Vasileios Askoxylakis, Alexey A Lugovskoy
PURPOSE: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Eunpi Cho, Qian Wu, Lena Rubinstein, Hannah Linden, Julie Gralow, Jennifer Specht, Vijayakrishna Gadi, Georgiana Ellis
Many studies have sought to optimize the dosing schedule of adjuvant chemotherapy in early-stage breast cancer. Here, we assessed the use of continuous metronomic weekly doxorubicin plus daily oral cyclophosphamide (AC) with continuous G-CSF growth factor support for 12 weeks followed by weekly nab-paclitaxel (nP) for 12 weeks. A nonrandomized phase II clinical trial was designed to assess (1) DFS at 2 years, (2) dose delivered, (3) use of nP in the adjuvant setting, and (4) toxicities. The dosing of A was 24 mg/m2 IV weekly and C was 60 mg/m2 oral daily (with scheduled filgrastim 5mcg/kg 6 days/week); nP, 100 mg/m2 IV weekly...
March 13, 2018: Breast Journal
Hiroshi Ishii, Natsumi Yamashita, Makoto Ueno, Shinichi Ohkawa, Akiko M Saito, Mitsugu Sekimoto
Introduction: In Japan, the age of patients with pancreatic cancer has increased. Combination chemotherapies such as 5-fluorouracil/leucovorin, oxaliplatin and irinotecan therapy and gemcitabine hydrochloride (GEM) +nab paclitaxel therapy have been developed as the standard treatments for young patients with advanced recurrent pancreatic cancer. However, both therapies produce toxicity and their administration is limited by the patients' age or performance status. The efficacy and safety data obtained in the GEST study-a large-scale randomised controlled study conducted in patients with pancreatic cancer in Japan-suggested that GEM +S-1 (GS) combination therapy is a promising candidate for those aged between 75 and 80 years...
2018: BMJ Open Gastroenterology
Jesus Vera-Aguilera, Agop Y Bedikian, Roland L Bassett, Wen-Jen Hwu, Kevin B Kim, Yong Qin, Suzanne Cain, Edwina W Washington, Michael A Davies, Sunil M Patel, Jade Homsi, Nicholas E Papadopoulos, Patrick Hwu, Sapna P Patel
OBJECTIVES: Hepatic arterial infusion (HAI) of cytotoxic chemotherapy is a strategy to deliver high dose of anticancer therapy to liver metastases that derive their blood supply from the hepatic artery. Metastatic melanoma (MM) has a high incidence of liver metastases, with uveal subtype in particular exhibiting a predilection for liver dissemination. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated efficacy in MM and first-pass hepatic metabolism. Therefore, we hypothesized that HAI of nab-paclitaxel would deliver an effective dose of drug to the end organ of interest, with minimal systemic exposure...
March 5, 2018: American Journal of Clinical Oncology
M Uccello, M Moschetta, G Mak, T Alam, C Murias Henriquez, H-T Arkenau
Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear...
February 2018: Current Oncology
Suguru Yamada, Tsutomu Fujii, Yukihiro Yokoyama, Hiroki Kawashima, Osamu Maeda, Kojiro Suzuki, Tohru Okada, Eizaburo Ono, Junpei Yamaguchi, Nao Takano, Hideki Takami, Masamichi Hayashi, Yukiko Niwa, Yoshiki Hirooka, Yoshiyuki Ito, Shinji Naganawa, Yuichi Ando, Masato Nagino, Hidemi Goto, Yasuhiro Kodera
PURPOSE: For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen. METHODS: Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined...
March 3, 2018: Cancer Chemotherapy and Pharmacology
Girolamo Ranieri, Ilaria Marech, Mariangela Porcelli, Francesco Giotta, Gennaro Palmiotti, Giuseppe Laricchia, Vito Fazio, Cosmo Damiano Gadaleta
About half of patients with metastatic breast cancer (mBC) have unresectable liver metastases (LMs) or liver-predominant disease (LPD). Unfortunately systemic chemotherapy has limited tumor response due to LMs are supplied by hepatic artery. Hepatic intra-arterial (HAI) have antitumor activity in pretreated patients with LMs. Here we report the case of a 55-year-old woman affected by BCLPD and heavily pretreated. LMs responded to treatment based on HAI with 5-fluorouracil and nab-paclitaxel systemic chemotherapy, and they completely disappeared on a CT-scan...
January 30, 2018: Oncotarget
Koji Kase, Ryo Okada, Makoto Muto, Junichiro Watanabe, Naoya Sato, Yasuhide Kofunato, Teruhide Ishigame, Takashi Kimura, Akira Kenjo, Tatsuo Shimura, Shigeru Marubashi
We hereby report a case of long-term survival of the pancreatic tail cancer with a synchronous small liver metastasis. A 62- year-old male with pancreatic tail cancer was incidentally diagnosed with single tiny metastasis in the left medial section of the liver duringthe distal pancreatectomy. The lesion was also resected together with primary lesion. Since then, systemic chemotherapies such as gemcitabine(GEM)plus S-1 combination therapy, GEM alone therapy and S-1 alone therapy had been given to escape from recurrence...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Taku Yasumoto, Kenji Uemoto, Koichi Yamada, Hakketsu Koh, Masaru Yamazaki, Norihisa Masai, Daisaku Tatsumi, RyoongJin Oh
A 70's man had been treated with gemcitabine(GEM)and nab-paclitaxel(nabPTX)combination for advanced pancreatic tail cancer with splenic invasion and liver metastases. However, the primary lesion was not controlled, then intensity-modulat- ed radiation therapy(76.5 Gy/17 Fr)was performed for primary lesion. Three grown hypovascular liver metastases were detected by follow-up EOB-MRI and PET-computed tomography(CT)imaging with 18F-FDG. Unfortunately, these lesions were not detected by intravenous injection of contrast media with CT nor ultrasonography...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yuuri Hatsuzawa, Masamichi Mizuma, Fuyuhiko Motoi, Tatsuo Hata, Masahiro Iseki, Tatsuyuki Takadate, Hideo Ohtsuka, Naoaki Sakata, Takanori Morikawa, Kei Nakagawa, Hiroki Hayashi, Takeshi Naitoh, Atsushi Kanno, Tooru Shimosegawa, Michiaki Unno
Here we report a case of pancreatic cancer(PC)with peritoneal dissemination, underwent conversion surgery following chemotherapy for 2 years. A5 5-year-old woman was referred to our hospital for treatment of PC. Abdominal CT scan revealed 3.0 cm of a pancreatic head tumor with abutment of the portal vein and the hepatic artery, classified as borderline resectable. Staging laparoscopy(SL)showed positive peritoneal cytology(CY). Gemcitabine(Gem)plus S-1 therapy(GS) was performed. Ten months after initial GS, SL revealed the disseminated nodule and positive CY...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Md Sazzad Hassan, Niranjan Awasthi, Jun Li, Fiona Williams, Margaret A Schwarz, Roderich E Schwarz, Urs von Holzen
Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC...
February 20, 2018: Translational Oncology
Yasuyuki Kojima, Hisanori Kawamoto, Toru Nishikawa, Ryosuke Hayami, Arata Shimo, Ei Haku, Kyoko Akiyama, Koichiro Tsugawa
BACKGROUND: Although several studies have shown efficacy of nanoparticle albumin-bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-three patients with no previous chemotherapy were enrolled to receive nab-paclitaxel 150 mg/m 2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment...
January 11, 2018: Clinical Breast Cancer
Reshma L Mahtani, Monika Parisi, Stefan Glück, Quanhong Ni, Siyeon Park, Corey Pelletier, Claudio Faria, Fadi Braiteh
Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab -paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA. Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab -paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014...
2018: Cancer Management and Research
Niranjan Awasthi, Sheena Monahan, Alexis Stefaniak, Margaret A Schwarz, Roderich E Schwarz
Nab-paclitaxel (NPT) combination with gemcitabine (Gem) represents the standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Genetic alterations of the RAS/RAF/MEK/ERK (MAPK) signaling pathway yielding constitutive activation of the ERK cascade have been implicated as drivers of PDAC. Inhibition of downstream targets in the RAS-MAPK cascade such as MEK remains a promising therapeutic strategy. The efficacy of trametinib (Tra), a small molecule inhibitor of MEK1/2 kinase activity, in combination with nab-paclitaxel-based chemotherapy was evaluated in preclinical models of PDAC...
January 12, 2018: Oncotarget
Naomi Mizuta, Tsutomu Nakagawa, Kazuhiro Yamamoto, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Ikuko Yano, Hironobu Minami, Midori Hirai
Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h...
July 20, 2017: Kobe Journal of Medical Sciences
Tetsuo Fujita, Takuma Hiroishi, Kohei Shikano, Asako Yanagisawa, Noriko Hayama, Hiroyuki Amano, Makoto Nakamura, Satoshi Hirano, Hiroshi Tabeta, Sukeyuki Nakamura
Background Although lung squamous cell carcinoma (SCC) accounts for 20%-30% of lung cancer cases, new treatment options are limited. The CA031 study showed that nanoparticle albumin-bound-paclitaxel (nab-PTX) plus carboplatin produced a significantly higher overall response rate (41%) than solvent-based paclitaxel plus carboplatin in patients with lung SCC. However, the safety and efficacy of combination chemotherapy of nab-PTX and carboplatin has not yet been established for patients with concurrent lung SCC and idiopathic interstitial pneumonias (IIPs)...
February 9, 2018: Internal Medicine
V Sgroi, M Bassanelli, M Roberto, E Iannicelli, R Porrini, P Pellegrini, A Tafuri, P Marchetti
Background: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer...
2018: Experimental Hematology & Oncology
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