Abstract:
:This article summarizes the likely attenuation properties of RRx-001 in COVID-19 based on its mechanism of action and the putative pathogenesis of the disease, which appears to activate inflammatory, oxidative, and immune cascades with the potential to culminate in acute respiratory distress syndrome, cytokine storm and death. An ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 appears to present with 3 major patterns of clinical symptomatology: (1) mild upper respiratory tract infection, (2) non-life-threatening pneumonia, and (3) severe pneumonia and acute respiratory distress syndrome that initially manifest as a mild prodrome lasting for 7-8 days before rapid clinical and radiological deterioration requiring ICU transfer. RRx-001 is a targeted nitric oxide donor. This small molecule, which has been evaluated in multiple Phase 1-2 clinical trials for cancer as well as a Phase 3 clinical trial for the treatment of small cell lung cancer called REPLATINUM (NCT03699956), is minimally toxic and demonstrates clear evidence of antitumor activity. During the course of these clinical trials it was noted that the rate of chronic obstructive pulmonary disease exacerbation and pneumonia in actively smoking small cell lung cancer patients treated with RRx-001 is less than 1%. Due to extensive history of tobacco use, 40%-70% of patients with lung cancer have chronic obstructive pulmonary disease and the expected rate of pulmonary infection in this population is 50%-70%, which was not observed in RRx-001 clinical trials. Moreover, in preclinical studies of pulmonary hypertension, RRx-001 was found to be comparable with or more effective than the FDA approved agent, Bosentan. The potential pulmonary protective effects of RRx-001 in patients with recurrent lung infections coupled with preclinical models demonstrating RRx-001-mediated reversal of pulmonary hypertension suggests RRx-001 may have therapeutic activity in patients with acute respiratory symptoms due to COVID 19. Clinical trials have been initiated to confirm the hypothesis that RRx-001 may be repurposed to treat SARS-CoV-2 infection.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Oronsky B,Knox S,Cabrales P,Oronsky A,Reid TRdoi
10.1053/j.seminoncol.2020.07.002subject
Has Abstractpub_date
2020-10-01 00:00:00pages
305-308issue
5eissn
0093-7754issn
1532-8708pii
S0093-7754(20)30079-8journal_volume
47pub_type
杂志文章abstract::The consistently high mortality rates associated with gastrointestinal cancer result in large part from malignancies that progress undetected to an advanced stage of disease when treatment is usually less effective. In response to this fact, increasing attention has been directed toward developing methods of both prim...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1991-02-01 00:00:00
abstract::Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, usually develops in a liver already suffering from chronic damages, often cirrhosis. There has been marked progress in the treatment of HCC. However, effective treatments are limited to patients with less advanced HCC. The detection of HCC at an...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2012.05.009
更新日期:2012-08-01 00:00:00
abstract::A number of cancers present with synchronous or metachronous hepatic metastases. Historically, many of these patients were considered unresectable and were treated with either systemic chemotherapy or supportive care. Today, a variety of options exist for the management of hepatic metastases. Newer agents for systemic...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.12.004
更新日期:2008-04-01 00:00:00
abstract::Ifosfamide was developed by investigators at Asta-Werke in Germany. Its chemical structure differs from that of cyclophosphamide by the transposition of one of the side chain chloroethyl groups to the ring nitrogen. In several preclinical models, ifosfamide had greater activity than cyclophosphamide. It produced less ...
journal_title:Seminars in oncology
pub_type: 历史文章,杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Locoregionally advanced unresectable non-small cell lung cancer is defined by bulky primary site disease and/or regionally advanced lymphadenopathy involving the contralateral mediastinum and/or supraclavicular lymph nodes. These tumors are not amenable to curative-intent surgical resection but can be approached with ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::Data from women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III or IV) were analyzed to evaluate the pharmacokinetic/pharmacodynamic relationships of carboplatin-based combination chemotherapy. With the equation area under the plasma concentration versus time curve (AUC) =...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-10-01 00:00:00
abstract::Recent advances in understanding tumor-specific immunity have introduced new excitement in the clinical development of vaccines for the treatment of cancer. A better understanding of basic immunologic principles has led to a variety of techniques for enhancing tumor-specific immunity through vaccination. Approaches to...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.09.006
更新日期:2005-12-01 00:00:00
abstract::Denileukin diftitox (ONTAK; Seragen Inc, San Diego, CA) is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that overexpress the IL-2 receptor. The human IL-2 receptor exists in three isoforms: low (CD25), intermediate (CD122/CD132), and high (CD25/CD122/CD132) affinity. The high-a...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.12.017
更新日期:2006-02-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown in vitro and clinical activity against non-small cell lung cancer and astrocytic brain tumors, tumors traditionally thought of as relatively resistant to chemotherapy and radiotherapy. Because of its ability to block dividing cells in the G2/M p...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::Phase I trials of the intraperitoneal (IP) administration of cisplatin have demonstrated that the drug can be safely delivered by this route with a major increase in exposure (approximately tenfold to 15-fold) of the cavity to the cytotoxic agent compared with that of the systemic circulation. Phase I trials of IP cis...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1989-08-01 00:00:00
abstract::Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is converted in vivo by endogenous phosphatases to the active drug etoposide. This conversion process is efficient and not saturable in humans at doses between 50 and 1,600 mg/m2. The resultant eto...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-12-01 00:00:00
abstract::From this brief review is should be evident that the hereditary varieties of common cancers are characterized by a high degree of genetic heterogeneity. The specific types of hereditary cancers can be identified by focusing on the histologic types and sites of involvement, not only of the primary neoplasm, but also of...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1978-03-01 00:00:00
abstract::Bendamustine has clinical potential in the treatment of low-grade non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been used in two studies in patients with relapsed or refractory low-grade NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the overall response rate was 73% with complete re...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.34877
更新日期:2002-08-01 00:00:00
abstract::Solid organ tumors associated with neoangiogenesis, as measured by increased microvessel density (MVD), have poorer prognoses. A similar observation of increased MVD has been made in hematologic malignancies; however, its prognostic significance remains unknown. We investigated changes in MVD in 122 newly diagnosed mu...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1016/s0093-7754(01)90025-9
更新日期:2001-12-01 00:00:00
abstract::Pharmacologic interventions for cancer risk reduction involve the chronic administration of synthetic or natural agents to reduce or delay the occurrence of malignancy. Despite the strong evidence for a favorable risk-benefit ratio for a number of agents in several common malignancies such as breast and prostate cance...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2015.09.014
更新日期:2016-02-01 00:00:00
abstract::Knowledge of the pharmacokinetics of a drug is essential to the optimal design of the dose and schedule of chemotherapy protocols. As an extension, an understanding of the mechanism of drug action is necessary to construct the optimal strategy for combination chemotherapy. Nucleoside antimetabolites such as fludarabin...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::Remarkable strides have been made in the management of infectious complications after bone marrow transplantation. Improved understanding of patterns of infection, the introduction of new antimicrobials, the advent of cytokines to enhance immune recovery, the development of better strategies to control graft-versus-ho...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::At present the only potentially curative treatment for hepatocellular carcinoma (HCC) is either partial hepatectomy or total hepatectomy with orthotopic liver transplantation (OLT). Underlying liver reserve and regenerative capacity are the most important determinants of the risk of postoperative hepatic failure after...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(01)90140-x
更新日期:2001-10-01 00:00:00
abstract::Angiogenesis is required for multistage carcinogenesis. The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. COX-2 expression occurs in a wide range of preneoplastic and malignant conditions; and the enzyme has been localized to the neoplastic cells, endothelial cell...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.03.040
更新日期:2004-04-01 00:00:00
abstract::The patient with metastatic adeno- or undifferentiated carcinoma who presents with a cryptic primary is subjected to an extensive diagnostic search. These efforts apparently stem from the following assumptions: 1). The ultimately proven primary sites in such patients will occur with the same frequency as the most comm...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Conventional cytogenetic studies have shown that the clinical and biological diversity of acute myeloid leukemia (AML) can be attributed, in part, to distinct chromosome aberrations, several of which are now routinely used for diagnosis, risk stratification, and outcome prediction. Although chromosome banding analysis...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2011.11.005
更新日期:2012-02-01 00:00:00
abstract::Predicting which patients with primary melanoma are at risk of developing metastastic disease is important for making rational therapeutic decisions. Tumor thickness alone is the most commonly used predictor of survival, but other clinical and pathologic variables also play an important role. We have developed two mul...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation of peripheral tolerance in order to prevent autoimmunity. Blocking of these cell surface proteins by antibodies has resulted in remarkable anti-tumor immunity; howev...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2015.02.011
更新日期:2015-06-01 00:00:00
abstract::The human gammaherpesvirus family includes Epstein-Barr virus (EBV) and human herpesvirus (HHV)-8, also known as Kaposi sarcoma-associated herpesvirus (KSHV). In human immunodeficiency virus (HIV)-infected patients, both EBV and KSHV have been implicated in the development of a wide range of tumors. KSHV-associated di...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.12.026
更新日期:2015-04-01 00:00:00
abstract::Intra-arterial (IA) therapies for hepatocellular carcinoma (HCC) are considered palliative and should be offered to patients with intermediate-stage multinodular disease and with sufficient liver reserve. They include transarterial chemoembolization (TACE) or bland embolization, transarterial chemotherapy, and transar...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.03.007
更新日期:2010-04-01 00:00:00
abstract::The current study was conducted to determine the risk of adverse outcomes among patients with monoclonal gammopathy of undetermined significance (MGUS) of the IgM class. Two hundred thirteen patients with IgM MGUS were identified in southeastern Minnesota from 1960 to 1994. The primary end point was progression to lym...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/sonc.2003.50062
更新日期:2003-04-01 00:00:00
abstract::Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was red...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-04-01 00:00:00
abstract::Pain is a common, feared, but treatable component of malignancy. The ability, however, to successfully relieve the difficult symptoms of progressive disease, including pain, require an understanding of tumor behavior, complications, and cancer therapy. Despite the treatability of cancer pain and multiple clinical opti...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1993-04-01 00:00:00
abstract::Lung cancer is the number one cause of cancer-related death in both men and women in the United States. Non-small cell lung cancer accounts for approximately 85% of these cases. Despite complete resection, long-term survival for patients with operable disease remains poor. Studies exploring postoperative chemotherapy ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(01)90056-9
更新日期:2001-08-01 00:00:00
abstract::Based on rigorous interpretation of current evidence, systemic therapy has two roles in the management of carcinoma of the uterine cervix. In patients with advanced or recurrent disease, single-agent chemotherapy constitutes the treatment of choice. The most extensively studied agents are the platinum compounds. Eithe...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1994-04-01 00:00:00