Expert opinion on investigational drugs
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This perspective is the last in a series of papers discussing drugs dropped from clinical development in 2006. Specifically, this paper focuses on the 16 drugs discontinued for the treatment of cancer, the largest area of pharma R&D. This was based on a search of the Pharmaprojects database for drugs reaching Phase I-III clinical trials.
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Expert Opin Investig Drugs · Feb 2008
ReviewCelecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs.
Celecoxib is an NSAID that was developed as a selective inhibitor of COX-2 and approved by the FDA for the treatment of various forms of arthritis and the management of acute or chronic pain. In addition, it was more recently approved as an oral adjunct to prevent colon cancer development in patients with familial adenomatous polyposis and is presently being investigated for its chemotherapeutic potential in the therapy of advanced cancers. However, in laboratory studies it was discovered that celecoxib was able to suppress tumor growth in the absence of any apparent involvement of COX-2, and additional pharmacologic activities associated with this drug were found. ⋯ This dualism enabled the synthesis of close structural analogs of celecoxib that exhibited increased antitumor potency in the absence of COX-2 inhibition. In theory, such compounds should be superior to celecoxib for antitumor purposes because they might reduce gastrointestinal and cardiovascular risks and the life-threatening side effects that appear during the long-term use of selective COX-2 inhibitors. In this review, the authors present the status of preclinical development of anticancer analogs of celecoxib that are COX-2 inactive, with an emphasis on 2,5-dimethyl-celecoxib (DMC) and OSU-03012.
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Expert Opin Investig Drugs · Jan 2008
ReviewOral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain.
Nabilone has been approved to treat chemotherapy-induced nausea and vomiting. Recent studies have explored cannabinoids in pain management. ⋯ Nabilone is superior to placebo, domperidone and prochlorperazine but not metoclopramide or chlorpromazine. Cannabinoids do not add to benefits of 5-HT(3) receptor antagonists. Side effects are greater for nabilone than for prochlorperazine, in most studies patients prefered nabilone over prochlorperazine. Nabilone is ineffective in acute pain but benefits in neuropathic pain and central hypersensitization. Recent guidelines place nabilone as a second to fourth line drug for neuropathic pain.
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Expert Opin Investig Drugs · Oct 2007
ReviewPixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin's lymphomas.
Pixantrone (BBR-2778) is a novel mitoxantrone-like drug, which lacks the 5,8-dihyroxy substitution groups thought to be responsible for the cardiac toxicity associated with mitoxantrone. In Phase I/II single-agent pixantrone clinical trials, neutropenia was the dose-limiting toxicity and the maximum tolerated dose was 150 mg/m(2)/week for 3 weeks every 4 weeks. ⋯ In the BBR-2778, methylprednisolone, cisplatin and cytosine arabinoside (BSHAP) regimen, 58% overall response and 37% complete response were achieved. A number of randomised studies of pixantrone (BBR-2778) in patients with relapsed indolent or aggressive lymphomas are ongoing.
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Neuropathic pain is a frequent condition that can result from a variety of underlying conditions and is frequently chronic and difficult to treat. A number of drugs are used to treat neuropathic pain, including anticonvulsants and antidepressants. ⋯ There is good evidence that oxcarbazepine is effective in relieving the pain associated with trigeminal neuralgia. Its efficacy in treating painful diabetic neuropathy is less clear; however, it seems to be useful when tolerated at doses of 1800 mg/day.