Year : 2011 | Volume
: 3 | Issue : 4 | Page : 546-
Ipilimumab: Melanoma and beyond
Vishal Patel1, Hardik Gandhi1, Aman Upaganlawar2,
1 Department of Pharmacy, Faculty of Technology and Enginnering, The Maharaja Sayajirao University Baroda, Vadodara, Gujarat, India
2 Department of Pharmacology, SSDJ College of Pharmacy, Neminagar, Chandwad, Dist-Nasik, India
Department of Pharmacy, Faculty of Technology and Enginnering, The Maharaja Sayajirao University Baroda, Vadodara, Gujarat
|How to cite this article:|
Patel V, Gandhi H, Upaganlawar A. Ipilimumab: Melanoma and beyond.J Pharm Bioall Sci 2011;3:546-546
|How to cite this URL:|
Patel V, Gandhi H, Upaganlawar A. Ipilimumab: Melanoma and beyond. J Pharm Bioall Sci [serial online] 2011 [cited 2020 Sep 25 ];3:546-546
Available from: http://www.jpbsonline.org/text.asp?2011/3/4/546/90113
Recently, USFDA has approved ipilimumab, a fully human monoclonal antibody, under the trade name Yervoy for the treatment of metastatic melanoma. Metastatic melanoma is one of the most common type of cancers, standing fifth while considering the frequency of occurrence of cancers. It is a type of skin cancer that demographically affects individuals in the fourth or fifth decade of their life. Incidence of the disease increases with age, and older men have the highest propensity of suffering from this disease. Primary risk factor for the occurrence of metastatic melanoma is prolonged exposure to UV in the range of 280 to 320 nm. Pathophysiology involves abnormal growth and proliferation of melanocytes in areas exposed to UV radiation. Full thickness ablative procedures are the primary modalities of treatment in such conditions, followed by radiation therapy. However, for patients in an advanced stage of the disease, surgical excision is not curative and they require adjunctive chemotherapy and immunotherapy.  IL-2 has been approved by the USFDA for immunotherapy in patients with metastatic melanoma. IL-2 stimulates cytotoxic T-lymphocytes which ultimately cause tumor cell lysis. A response rate of about 16% is achieved with this modality of treatment. Another drug approved for the treatment of this condition is dacarbazine, achieving an overall response rate of up to 25%. However, both the alternatives have their own shortcomings (chronic side effects, need to monitor laboratory functions, relapsing disease).  To prevail over this condition, Bristol-Myers Squibb (BMS) has come up with ipilimumab which is a fully human monoclonal antibody (IgG1 isotype).
Ipilimumab is directed against the CTLA-4 antigen present on the surface of cytotoxic T-lymphocytes. Presence of the CTLA-4 antigen negatively regulates the activity T-lymphocytes, ultimately suppressing the immune response. So, blocking the CTLA-4 antigen with ipilimumab will stimulate the patient's own immune response which will be helpful in destroying cancerous cells.  Ipilimumab has been studied in more than 2 000 patients with metastatic melanoma and response patterns show shrinkage of baseline lesions, decline of tumor burden with a complete response in a few patients. An objective response rate of above 30% was observed in later stages of clinical trials after failing the initial response rate threshold (10%) in the initial stages. The results of the advanced phase III trials indicate that one-third of the patients taking ipilimumab will receive long-term survival benefits.  On the flip side, ipilimumab comes with a boxed warning concerning the immune-mediated adverse reactions. It has been advised to discontinue the use of ipilimumab in case of occurrence of immune-mediated enterocolitis, hepatitis, dermatitis, or neuropathy. Usually, these adverse effects manifest during therapy but in some cases late manifestations have been observed.  Other common side effects include rashes and diarrhea. Based on the animal studies, it has been found to cause fetal damage and hence contraindicated in pregnant females.
Not only this, ipilimumab has some other ramifications with regard to its role against cancer. It has been reported to shrink hormone refractory prostate cancers in a few patients. Even though this effect was only observed in combination with other therapies, further clinical trials are necessitated for conforming this effect. Ipilimumab has also been implicated in lung cancers and renal carcinoma.  Moreover, BMS has already started trials of ipilimumab for treatment of lung cancers. Since it affects the immune system, it may find a viable alternative in the therapy of small-cell lung cancer and non-small-cell lung cancer (NSCLC). BMS has recently announced the beginning of Phase III trials of ipilimumab in NSCLC.
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