Cancer Treatment Today

Ontak is a recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B followed by the sequences for interleukin-2. The FDA approved Ontak as an orphan drug in February 1999 for treatment of cutaneous T-cell lymphoma. Ontak is in clinical trials for melanoma; for example, Phase II Trial of Ontak With Metastatic Melanoma, NCT00299689. The purpose of this study is to determine whether ONTAK is an effective treatment in patients with Stage IV Melanoma.

A Czech study presented in 2006 suggested prelimiarily that Ontak may be suedul for melanoma; five out of seven patients with stage IV disease experienced significant regression or stabilisation of both tumours and metastases. The two other patients in whom the disease progressed were on a lower dose of the drug. All the patients are still alive after 12 months. Imn the same year,two patients were presented at ASCO. There are also studies combinaing Ontak with vaccines.

Dummer, Reinhard Emerging drugs in cutaneous T-cell lymphomas
Expert Opinion on Emerging Drugs, Volume 10, Number 2, 1 May 2005 , pp. 381-392(12)

EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics (Thursday 9 November, 2006, Abs 264

DAB(389)IL2 (Denileukin Diftitox; ONTAK) suppresses growth of melanoma metastases.Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 18010

Approximately 6-12% of melanoma cases are hereditary, and may have a strong link to the development of pancreatic cancer. The gene responsibel for this type of melanoma is autosomal dominant and located on chromosome 9p21. This gene, called p16 (also known as CDKN2A, INK4A, or MTS1), accounts for up to 40% of hereditary melanoma cases. It is a tumor suppressor gene involved in regulating cell growth.

Currently, identification of teh P16 gene is not clinically significant. All individuals considered at high risk for melanoma should be managed similarly regardless of p16 mutation status. Individuals at increased risk for melanoma should be identified. Family history information should be obtained from all individuals with melanoma or dysplastic nevi, and first-degree relatives should be screened because of the increased risk of CMM in melanoma-prone families in any case. These individuals should be educated about sun protection, avoidance of intense sun exposure, and other preventive measures, such as learning how to detect dysplastic nevi characteristics and melanoma warning signs.

Management recommendations also include examination of the entire skin surface by a skilled healthcare provider every 6 months from 10 years, or earlier for suspicious nevi, until nevi are stable and annually thereafter.

Similarly there are no guidelines that recommend pancreatic cancer screening based on identification of the p 16 mutation.
http://www.moffitt.org/moffittapps/ccj/v4n1/department2.html (Guidelines)

Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351:998-1012.

Parker JF, Florell SR, Alexander A, DiSario JA, Shami PJ, Leachman SA.
Pancreatic carcinoma surveillance in patients with familial melanoma. Arch Dermatol. 2003 Aug;139(8):1019-25.