Celebrex

Property	Information
Drug Name	Celebrex (Celecoxib) and Other NSAIDs
FDA Approval	Yes (Celebrex is FDA-approved for arthritis and pain, but not specifically for cancer treatment)
Used for	Investigational use in cancer treatment due to anti-inflammatory, anti-angiogenic, and potential tumor growth inhibition properties
Clinical Trial Phase	Early clinical trials and observational studies, including phase 2 trials combining Celebrex with conventional cancer treatments
Clinical Trial Explanation	Not specified
Common Side Effects	Generally well-tolerated; potential gastrointestinal issues with long-term use of some NSAIDs. Celebrex designed to minimize COX-1 inhibition and related stomach issues.
OS without	Not specified
OS with	Not specifically documented; clinical trials have shown mixed results, with some indicating significant benefit when added to standard chemotherapy protocols
PFS without	Not specified
PFS with	Variable across studies; for example, a study combining Temodar with Celebrex showed a PFS-6 of 35%, another combining Celebrex with CPT-11 showed PFS-6 of 25%
Usefulness Rating	3
Usefulness Explanation	Not specified
Toxicity Level	2.5
Toxicity Explanation	The toxicity level of 2.5 indicates that Celecoxib (Celebrex) and other NSAIDs have a moderate level of side effects, which are mostly related to potential stomach issues with long-term use. However, Celebrex has been designed to minimize these issues. Even though their use in cancer treatment is experimental, these drugs are generally well-tolerated. A toxicity level of 5 would represent a treatment with severe and frequent side effects.

Notes: The use of Celebrex and other NSAIDs in cancer treatment is based on their anti-inflammatory properties, inhibition of COX-2 enzymes, and subsequent reduction in angiogenesis and tumor growth. While preclinical and early clinical research indicates potential benefits, including immune system enhancement and apoptosis induction, results from clinical trials have been mixed. The mechanisms underlying NSAIDs' anti-cancer effects, particularly in gliomas, suggest a promising avenue for research, emphasizing the need for further large-scale, randomized clinical trials to better understand their efficacy and optimal integration into cancer therapy regimens.

From Ben Williams Book: Celebrex (and other NSAIDs)

Carcinogenesis of several types involves an inflammatory process. When anti- inflammatory drugs such as aspirin or ibuprofen are taken on a regular basis the incidence of colon cancer is reduced as much as 50%. This substantial effectiveness has motivated investigation of the mechanisms of these benefits. One component of the inflammatory process is angiogenesis, which is now believed to be a critical component of cancer growth. COX-2 enzymes play an important role in inflammation, so that COX-2 inhibitors should reduce angiogenesis and inhibit tumor growth. Many nonsteroidal anti- inflammatory drugs (NSAIDs) are known to be COX-2 inhibitors, but most (e.g., ibuprofen) also inhibit COX-1 enzymes, which are necessary for healthy maintenance of the stomach lining, which is why many users of NSAIDs eventually develop intolerance to them. Thus, much recent attention has been given to the new COX-2 inhibitors such as Celebrex that were developed to avoid COX-1 inhibition for the purposes of arthritis treatment. Because inhibition of angiogenesis is one of the major new approaches to the treatment of cancer, some oncologists have begun adding Celebrex to their regular treatment protocols, based on laboratory findings that COX-2 inhibitors inhibit tumor growth. In recent meetings of American Society for Clinical Oncology (ASCO), there

have been various clinical trials reported that combined one or another COX-2 inhibitor with conventional radiation, chemotherapy, and new targeted treatments. The great majority of these were phase 2 clinical trials which had only historical controls with the conventional treatment alone to assess the value of the added COX-2 inhibitors, but most concluded there appeared to be a significant benefit, Some larger randomized clinical trials (115, 116) have shown substantial outcome improvements when celebrex has been added to standard chemotherapy protocols, but others have failed to find a benefit.

Two clinical trials have been reported that have used celebrex in the treatment of gliomas In a clinical trial conducted jointly by several hospitals in New York, Temodar was combined with celebrex (117). For the 46 patients in the study (37 with GBM), the PFS-6 was 35%. However, an unusual schedule of Temodar was also used, so whether the results were due to the new schedule or the celebrex is uncertain. Celebrex has also been combined with CPT-11 (118), a chemotherapy agent used widely for colon cancer, with �patients with recurrent tumors, and produced a PFS-6 value of 25%.

Because of the mild toxicity of NSAIDS, considerable recent research has investigated the mechanisms of their clinical benefit. Whereas initial research focused on the anti- angiogenic properties of this class of drugs, several other mechanisms have been identified, including the enhancement of various aspects of the immune system, and inhibition of the genes that prevent damaged cells from undergoing apoptosis (119). It is critical to note that many of the mechanisms by which NSAIDS work are strongly involved in the growth of high-grade gliomas, and that the expression of the cyclooxygenase enzyme that is the target of COX-2 inhibitors correlates strongly with the proliferation rate of glioblastoma tumors and correlates inversely with survival time (120, 121).Property "Has original text" (as page type) with input value "Celebrex (and other NSAIDs)</br></br>Carcinogenesis of several types involves an inflammatory process. When anti-</br>inflammatory drugs such as aspirin or ibuprofen are taken on a regular basis the</br>incidence of colon cancer is reduced as much as 50%. This substantial effectiveness has</br>motivated investigation of the mechanisms of these benefits. One component of the</br>inflammatory process is angiogenesis, which is now believed to be a critical component of</br>cancer growth. COX-2 enzymes play an important role in inflammation, so that COX-2</br>inhibitors should reduce angiogenesis and inhibit tumor growth. Many nonsteroidal anti-</br>inflammatory drugs (NSAIDs) are known to be COX-2 inhibitors, but most (e.g.,</br>ibuprofen) also inhibit COX-1 enzymes, which are necessary for healthy maintenance of</br>the stomach lining, which is why many users of NSAIDs eventually develop intolerance</br>to them. Thus, much recent attention has been given to the new COX-2 inhibitors such as</br>Celebrex that were developed to avoid COX-1 inhibition for the purposes of arthritis</br>treatment. Because inhibition of angiogenesis is one of the major new approaches to the</br>treatment of cancer, some oncologists have begun adding Celebrex to their regular</br>treatment protocols, based on laboratory findings that COX-2 inhibitors inhibit tumor</br>growth. In recent meetings of American Society for Clinical Oncology (ASCO), there</br></br>have been various clinical trials reported that combined one or another COX-2 inhibitor</br>with conventional radiation, chemotherapy, and new targeted treatments. The great</br>majority of these were phase 2 clinical trials which had only historical controls with the</br>conventional treatment alone to assess the value of the added COX-2 inhibitors, but most</br>concluded there appeared to be a significant benefit, Some larger randomized clinical</br>trials (115, 116) have shown substantial outcome improvements when celebrex has been</br>added to standard chemotherapy protocols, but others have failed to find a benefit.</br></br>Two clinical trials have been reported that have used celebrex in the treatment of gliomas</br>In a clinical trial conducted jointly by several hospitals in New York, Temodar was</br>combined with celebrex (117). For the 46 patients in the study (37 with GBM), the PFS-6</br>was 35%. However, an unusual schedule of Temodar was also used, so whether the results</br>were due to the new schedule or the celebrex is uncertain. Celebrex has also been</br>combined with CPT-11 (118), a chemotherapy agent used widely for colon cancer, with</br>�patients with recurrent tumors, and produced a PFS-6 value of 25%.</br></br>Because of the mild toxicity of NSAIDS, considerable recent research has investigated</br>the mechanisms of their clinical benefit. Whereas initial research focused on the anti-</br>angiogenic properties of this class of drugs, several other mechanisms have been</br>identified, including the enhancement of various aspects of the immune system, and</br>inhibition of the genes that prevent damaged cells from undergoing apoptosis (119). It is</br>critical to note that many of the mechanisms by which NSAIDS work are strongly</br>involved in the growth of high-grade gliomas, and that the expression of the</br>cyclooxygenase enzyme that is the target of COX-2 inhibitors correlates strongly with the</br>proliferation rate of glioblastoma tumors and correlates inversely with survival time (120,</br>121)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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