Appeal type: Experimental/Investigational
Decision: Upheld

Physician 1: This patient is a 51-year-old male diagnosed with malignant melanoma of the scalp in June 2002, treated surgically. In July 2003 he was found to have involvement of the lymph nodes in his neck, which were resected. This was followed by one year of interferon therapy. In May 2005 the patient was found to have involvement of his spleen and left hilar area; he was treated with biochemotherapy, including Temodar, platinol vinblastine, interleukin-2 (IL-2), and interferon. There was no response. He was then treated with an experimental agent, MDX-010, with again, no response. He next was treated with chemotherapy including carboplatinum, Taxol, and sorafenib, again with progression of disease.It is now proposed that the patient be treated with high dose IL-2 along with taurolidine. This treatment is the subject of a clinical trial in Dublin, Ireland. The Health Plan has denied authorization for the requested therapy on the basis that it is considered investigational.Taurolidine, a derivative of the amino acid taurine, has been used in Europe. One of the submitted articles details the treatment of eleven patients with metastatic melanoma with high dose IL-2 and taurolidine. The intent of the taurolidine was to ameliorate the known severe potential toxicity of the high dose IL-2 without abrogating its anti-tumor effects.Of the eleven patients, seven died from progressive cancer. Two others are alive but with progressive cancer. Two, however, did have complete remission lasting thus far, 8 and 55 months. The toxicity of the treatment did appear to be significantly less than would have been expected from IL-2. The conclusion of the authors of this small trial was that taurolidine might ameliorate the expected toxicity of high dose IL-2, and that this observation should be extended into a randomized trial.It is noted that the patients treated in the reported trial received fairly minimal systemic treatment prior to their treatment with IL-2 and taurolidine. This patent has received extensive treatment with a variety of chemotherapeutic agents, including IL-2 itself, though admittedly not in high dose. Thus, the patient is not at all comparable to those in the OBrien study and he would not be expected to experience the same degree of benefit. Furthermore, this is clearly a very small trial, of selected patients, and is non-randomized; an important consideration pointed out even by the authors of the trial themselves.Accordingly, the use of taurolidine with high dose IL-2 must be considered investigational and of no proven benefit for this patient. Therefore, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld.Physician 2: The patient is a 51-year-old male with visceral metastatic melanoma refractory to biochemotherapy treatment (including interleukin-2) followed by carboplatin, taxol and sorafeni. He now wishes to receive high dose interleukin-2 with taurolidine. The Health Plan has denied authorization and coverage indicating the efficacy of the proposed therapy has not been established.There is inadequate support in the medical literature for the proposed therapy. The submitted materials include several pre-clinical abstracts that are not directly relevant to interleukin-2 for treatment of melanoma. Additionally, the submitted pre-clinical publication is not relevant to the proposed regimen. A very small pilot study without formal phase II or phase III or independent review does not prove there is any benefit to the suggested therapy. Accordingly, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. Therefore, the Health Plans denial should be upheld.Physician 3: A 51-year-old male with stage IV melanoma is appealing denial of coverage for participation in a clinical trial using high dose interleukin-2 (IL-2) together with taurolidine, which is licensed in Europe but is not in clinical use in the United States. The Health Plan had denied authorization for the requested therapy on the basis that it is considered experimental.A detailed search of the literature including the NCCN guidelines and UpToDate does not add to the literature base submitted by the patients provider.  The peer-reviewed status of the Ireland group is limited to an Irish medical journal, and the report itself is of a limited nature with very small patient numbers. The clinical trial has not been vetted or sponsored by an American clinical research organization or the National Cancer Institute. Furthermore, taurolidine has not been evaluated in the United States.  Although one of the arguments of the proponents of the therapy is that the concurrent administration of taurolidine will limit the necessity for intensive unit care, in fact, detailed guidelines regarding the administration of high dose IL-2 (from the manufacturer/Proleukin) have enabled many tertiary care medical centers to care for patients on this regimen on a cancer care ward with experienced nursing staff. Thus, it has not been established that the proposed therapy (high dose IL-2 plus taurolidine) is likely to be more beneficial in terms of safety and efficacy than the available standard of care.Based upon the information set forth above, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. Therefore, the Health Plans denial should be upheld.