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Jean-Yves Blay
Surgery (+ radiation therapy in selected cases) is standard treatment for adult-type localized soft tissue sarcoma (STS). Accumulating randomized clinical evidence also supports adjuvant chemotherapy as a treatment option, although this remains contentious. Doxorubicin (± ifosfamide) is the standard first-line systemic treatment for advanced STS; however, newer chemotherapeutic agents may improve outcomes achieved with single-agent doxorubicin. In a Phase II study, adding olaratumab to doxorubicin markedly improved overall survival...
May 2018: Future Oncology
Jun Gong, Jessica Yan, Charles Forscher, Andrew Hendifar
Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload...
2018: Drug Design, Development and Therapy
Esha Sachdev, Divesh Sachdev, Monica Mita
Intoduction: Soft tissue sarcomas (STS) encompass a group of rare tumors arising from mesenchymal tissue. Traditionally, anthracycline-based chemotherapy, with doxorubicin, is the main treatment for advanced STS. Areas covered: Aldoxorubicin is a doxorubicin derivative containing a carboxylic hydrazone and serves as a prodrug of doxorubicin. It covalently binds to albumin in the blood until reaching the acidic tumor environment, which dissolves the hydrazone linker, thus releasing doxorubicin into the tissue...
October 2017: Expert Opinion on Investigational Drugs
Jennifer Y Sheng, Sujana Movva
Soft tissue sarcomas are rare tumors that present with distant metastasis in up to 10% of patients. Survival has improved significantly because of advancements in histologic classification and improved management approaches. Older agents such as doxorubicin, ifosfamide, gemcitabine, and paclitaxel continue to demonstrate objective response rates from 18% to 25%. Newer agents such as trabectedin, eribulin, aldoxorubicin, and olaratumab have demonstrated improvements in progression-free survival, overall survival, or toxicity profiles...
October 2016: Surgical Clinics of North America
Rashmi Chugh, Scott M Schuetze
No abstract text is available yet for this article.
December 2015: JAMA Oncology
Sant P Chawla, Zsuzsanna Papai, Guzel Mukhametshina, Kamalesh Sankhala, Leonid Vasylyev, Alexander Fedenko, Kenneth Khamly, Kristen Ganjoo, Rajnish Nagarkar, Scott Wieland, Daniel J Levitt
IMPORTANCE: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies. OBJECTIVE: To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma. DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices...
December 2015: JAMA Oncology
David A Liebner
Conventional chemotherapy can have a favorable impact on the natural history of disease for selected patients with primary high-risk bone and soft-tissue sarcomas. In particular, multidrug regimens are integral to the care of patients with the most aggressive histologies, including Ewing sarcoma, osteosarcoma, and non-pleomorphic rhabdomyosarcoma. Appropriately selected patients with high-risk, clinically localized soft-tissue sarcomas may also benefit from histology-tailored adjuvant or neoadjuvant therapy...
April 2015: Journal of Surgical Oncology
Monica M Mita, Ronald B Natale, Edward M Wolin, Brenda Laabs, Hillary Dinh, Scott Wieland, Daniel J Levitt, Alain C Mita
Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. Purpose This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine). Methods Eighteen patients with advanced solid tumors received aldoxorubicin 230 or 350 mg/m(2) (equivalent in drug load to doxorubicin at doses of 170 or 260 mg/m(2), respectively) once every 21 days...
April 2015: Investigational New Drugs
Luis Marrero, Dorota Wyczechowska, Alberto E Musto, Anna Wilk, Himanshu Vashistha, Adriana Zapata, Chelsey Walker, Cruz Velasco-Gonzalez, Christopher Parsons, Scott Wieland, Daniel Levitt, Krzysztof Reiss, Om Prakash
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues...
October 2014: Neoplasia: An International Journal for Oncology Research
Sant P Chawla, Victoria S Chua, Andrew F Hendifar, Doris V Quon, Neelesh Soman, Kamalesh K Sankhala, D Scott Wieland, Daniel J Levitt
BACKGROUND: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD). METHODS: Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m(2) , 350 mg/m(2) , or 450 mg/m(2) (170 mg/m(2) , 260 mg/m(2) , or 335 mg/m(2) doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles...
February 15, 2015: Cancer
Hyojin Moon, Jisu Lee, Junseon Min, Sebyung Kang
Protein cage nanoparticles are excellent candidates for use as multifunctional delivery nanoplatforms because they are built from biomaterials and have a well-defined structure. A novel protein cage nanoparticle, encapsulin, isolated from thermophilic bacteria Thermotoga maritima, is prepared and developed as a versatile template for targeted delivery nanoplatforms through both chemical and genetic engineering. It is pivotal for multifunctional delivery nanoplatforms to have functional plasticity and versatility to acquire targeting ligands, diagnostic probes, and drugs simultaneously...
October 13, 2014: Biomacromolecules
Felix Kratz
Human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents, primarily for treating diabetes and cancer, improving the pharmacokinetic profile of the drug or delivering the drug to the pathogenic site addressing diseases with unmet medical needs. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir, Tresiba, and Victoza) which bind physically to the respective binding sites of HSA thus extending their half-life. For cancer treatment, the paclitaxel albumin nanoparticle Abraxane has been approved for treating metastatic breast cancer, non-small cell lung cancer, and advanced pancreatic cancer...
September 28, 2014: Journal of Controlled Release: Official Journal of the Controlled Release Society
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