Expert Opinion on Investigational Drugs

Our medical research library holds 6 studies published in Expert Opinion on Investigational Drugs (2002–2019). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Taylor & Francis
• Published: 1994 to the present, England
• Language: English
• ISSN: 1354-3784 (print), 1744-7658 (electronic)
• Continues: Current Opinion in Investigational Drugs
• Its record in the NLM Catalog

2010s

• What can independent research for mesothelioma achieve to treat this orphan disease?. A. Guazzelli, P. Meysami, E. Bakker, et al. 2019;28(8):719-732. Review PubMed · Publisher

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.

• Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma. A. Guazzelli, E. Bakker, K. Tian, et al. 2017;26(8):933-944. Review PubMed · Publisher

  Abstract

  Malignant mesothelioma is a rare and lethal malignancy primarily affecting the pleura and peritoneum. Mesothelioma incidence is expected to increase worldwide and current treatments remain ineffective, leading to poor prognosis. Within this article potential targets to improve the quality of life of the patients and assessment of further avenues for research are discussed. Areas covered: This review highlights emerging therapies currently under investigation for malignant mesothelioma with a specific focus on phase I and phase II clinical trials. Three main areas are discussed: immunotherapy (immune checkpoint blockade and cancer vaccines, among others), multitargeted therapy (such as targeting pro-angiogenic genes) and gene therapy (such as suicide gene therapy). For each, clinical trials are described to detail the current or past investigations at phase I and II. Expert opinion: The approach of applying existing treatments from other cancers does not show significant benefit, with the most promising outcome being an increase in survival of 2.7 months following combination of chemotherapy with bevacizumab. It is our opinion that the hypoxic microenvironment, the role of the stroma, and the metabolic status of mesothelioma should all be assessed and characterised to aid in the development of new treatments to improve patient outcomes.

• The current state of pemetrexed in ovarian cancer. R.E. Miller, S. Banerjee. 2013;22(9):1201-10. Review PubMed · Publisher

  Abstract

  Introduction: Pemetrexed is a multitargeted antifolate drug that has shown benefit in several clinical trials in solid tumors. It is currently approved for the treatment of nonsmall cell lung cancer (NSCLC) and mesothelioma, and is being explored in epithelial ovarian cancer.

  Areas Covered: In this article, the clinical development of pemetrexed in relation to ovarian cancer is discussed. Early phase clinical trials using pemetrexed monotherapy or in combination with other cytotoxic or target agents are reviewed. The safety profile of pemetrexed will also be evaluated.

  Expert Opinion: A number of Phase I and II clinical trials have evaluated the use of pemetrexed in patients with ovarian cancer. Thus far, there are no randomized studies that address the role of pemetrexed compared to current, standard treatments. The activity of single agent pemetrexed in platinum-resistant patients is worth exploring. Biomarker-driven randomized, clinical trials and patient selection are key for the future development of pemetrexed.

• Therapies currently in Phase II trials for malignant pleural mesothelioma. G. Pinton, A.G. Manente, D. Tavian, et al. 2013;22(10):1255-63. Review PubMed · Publisher

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure, whose incidence will peak within the next years. Despite an overall low response rate, the current first-line therapy is represented by combined chemotherapy with cisplatin and antifolate. Moreover, there are no currently approved regimens for relapsed or refractory MPM. Therefore, it is clear how both preclinical and clinical researches aimed at identifying new therapeutic targets and testing them in early clinical settings are badly needed.

  Areas Covered: The aim of this review is to summarize and critically comment the ongoing Phase II trials for MPM.

  Expert Opinion: Over the past few years, there has been a significant endeavor of addressing the clinical research for MPM beyond the very modest results of chemotherapy. Nonetheless, our understanding is that the treatment of MPM should not be merely 'copied' from that of other much better studied tumors. In the light of recent results, studies toward the metabolic characteristics of this tumor are being progressively addressed. These evidences are disclosing a rather unusual model of malignancy, very likely to be more sensitive to novel 'MPM cells- and microenvironment-tailored' therapy addressing these characteristics rather than the sole cancer proliferation.

• Anti-angiogenic therapies for malignant pleural mesothelioma. G.L. Ceresoli, P.A. Zucali. 2012;21(6):833-44. Review PubMed · Publisher

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is a disease with a dismal prognosis. Currently available treatments have modest results. Therefore, new agents and new treatment strategies are eagerly awaited by patients and clinicians. Preclinical and clinical studies have shown that angiogenesis plays a very important role in MPM. Therefore, a great hope has been placed in the use of anti-angiogenic agents in this disease.

  Areas Covered: Studies regarding anti-angiogenic treatments in MPM with bevacizumab, tyrosine-kinase inhibitors (TKIs) and other agents were critically analyzed, with an overview of ongoing trials and future perspectives, including research on biomarkers.

  Expert Opinion: The clinical use of angiogenesis inhibitors in MPM patients has resulted more challenging than anticipated. The intrinsic complexity of neo-angiogenesis, and its redundant regulatory mechanisms, suggests that multiple and different biomarkers are needed to predict efficacy of anti-angiogenic agents and to monitor their biological and therapeutic effects. The growing understanding of the molecular alterations and key pathways that underlie the resistance to VEGF inhibitors will allow to design studies of the combination of agents targeting these pathways with anti-VEGF therapies. Only a tight integration of preclinical and clinical studies will allow to achieve a real progress in MPM patients with this therapeutic strategy.

2000s

• Future potential of thymidylate synthase inhibitors in cancer therapy. N.L. Lehman. 2002;11(12):1775-87. Review PubMed · Publisher

  Abstract

  Thymidylate synthase (TS) catalyses the de novo synthesis of deoxythymidylate and is a key rate-limiting enzyme of DNA synthesis. The primary site of action of the classic antifolate methotrexate is direct inhibition of dihydrofolate reductase, but it also inhibits TS indirectly by diminishing levels of the TS cosubstrate 5,10-methylenetetrahydrofolate. Polyglutamated metabolites of methotrexate also directly bind and inhibit TS. The prototype fluoropyrimidine fluorouracil is metabolised to an irreversible inhibitor of TS and is the standard chemotherapy for gastrointestinal carcinomas. It is also frequently used in combination with other anticancer drugs against breast cancer and head and neck cancers. The clinical efficacy of fluorouracil is routinely increased by concomitant administration of the biomodulating compound leucovorin (folinic acid). Both the success and limitations of these early drugs led to a search for new, more efficacious TS inhibitors active against a broader range of neoplasms. Raltitrexed (ZD1694, Tomudex) is an antifolate TS inhibitor developed over the last decade that is similarly effective, yet better tolerated, than fluorouracil against colorectal cancer. Additional antifolate and fluoropyrimidine-based TS inhibitors continue to be developed. Many of these experimental drugs have been designed to exploit or thwart selective metabolism in neoplasms, including specific mechanisms of resistance. As the curative potential of relatively non-selective antiproliferative drugs like TS inhibitors is limited against most neoplasms, the future role of TS inhibitors will likely continue to be adjunctive in surgically resectable tumours and palliative in combination with other agents for non-resectable disease. Although TS inhibitors will eventually be supplanted by yet to be discovered agents targeting more tumour-specific cellular signalling pathways, they will probably remain important for the above uses for some time. Future advances in the effective use of TS inhibitors may be forthcoming in the form of improved dosing, fewer untoward effects and increased tumour selectivity with novel fluorouracil prodrug formulations. Furthermore, there is emerging evidence that some novel antifolate TS inhibitors are active against a broader range of neoplams, including lung carcinomas and mesothelioma, compared to classical TS inhibitors. Other possible advances to come include effective biomodulation of antifolate TS inhibitors with nucleoside transport inhibitors and individualised patient therapy based on tumour gene expression and resistance patterns (pharmacogenetics).

Browse every journal in the library or the library by type of article, or return to medical research.