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____________________________________ In the Matter of the Internal Appeal of JOHN DOE, AFFIRMATION OF TREATING PHYSICIAN BETTY A. SMITH, M.D. (Concerning coverage for Bevacizumab and Irinotecan) ______________________________________ STATE OF NEW YORK I, Dr. Betty Smith, M.D., under penalty of perjury, attest as follows: 1. I am a Neuro-oncologist at New York Oncology Hematology, P.C. (hereinafter “NYOH”), and I specialize in neurology and neuro-oncology. I am Board certified by the American Board of Psychiatry and Neurology. I make this affirmation in support of an Appeal of the denial of medical service authorization of Avastin/CPT-11 treatment against my patient, John Doe (“Mr. Doe”). 2. This affirmation outlines my clinical findings and professional opinion concerning why treatment with Avastin/CPT-11 is appropriate, safe, and often used when other treatments have been ineffective. It also sets forth new information showing promising initial clinical and functional results for Mr. Doe from the Avastin/CPR-11 treatment for which he has been paying with the help of family and friends. 1 Actual names and other identifying information modified to protect confidentiality. 3. My opinion, as his treating physician, is that Empire Blue Cross’ decision to deny insurance coverage for this treatment is not only wrong, but is causing harmful stress to Mr. Doe and his family and jeopardizing his future access to appropriate treatment. 4. The information set forth herein is true to the best of my knowledge based upon my professional experiences, personal knowledge, and review of medical literature related to 5. On October 19, 2006, Dr. David Brown, Associate Professor of Neurosurgery at Albany Medical College and Board certified by the American Board of Neurological surgery, referred Mr. Doe to me for evaluation of a right parietal glioblastoma multiforme. Mr. Doe is a right-handed, middle-aged owner of his own business. 6. Mr. Doe’s symptoms, referable to this diagnosis, date back to January 2006 when he developed left-sided tingling and thought to have had a possible transient ischemic attack (TIA) or seizure. Imaging studies yielded a non-enhancing primary glioma in the right parietal region. Dr. Brown performed a debulking procedure on March 29, 2006 and found a low-grade astrocytoma with increased celluarity but no evidence of mitosis, necrosis, or microvascular proliferation. 7. On or about September 17, 2006, Mr. Doe had another episode of tingling in his left hand and had a recurrent focal sensory seizure. An MRI taken at that time, which is attached as “Attachment 1,” revealed the progressive disease of gemistocytic small cell
glioblastoma. Specifically, Mr. Doe had suffered hemorrhaging in the surgical cavity and 8. On September 20, 2006, Mr. Doe had a second craniotomy that revealed high-grade astrocytoma. During the surgery, Dr. Brown treated Mr. Doe with gliadel wafers, an anti-cancer chemotherapy drug, because of the indicated possibility of a malignant glioma. The final pathology of Mr. Doe was a high-grade glioblastoma with evidence of microvascular proliferation, tumor necrosis, and mitotic activity. Mr. Doe’s diagnosis also noted to have gemistocytic and small-cell features in his specimen. 9. Dr. Brown arranged for Mr. Doe to have chemoradiation therapy. Mr. Doe would have the radiation therapy at Glens Falls Hospital and the chemotherapy at NYOH. 10. On September 29, 2006, Mr. Doe had a second concurring opinion from Dr. Janet Foe, M.D. at Memorial Sloan-Kettering Cancer Center and Board certified by the American Board of Psychiatry and Neurology, to undertake the radiation therapy and the Temodar chemotherapy. Dr. Foe’s consultation is attached as “Attachment 2.”
11. In October of 2006, Mr. Doe started a course of radiation therapy at Glen Falls Hospital in Glen Falls, NY and a low-dose of Temodar chemotherapy at NYOH. 12. On November 4, 2006, Mr. Doe began treatment with Temodar, Zofran, and Bactrim. He took Temodar with the radiation for the last 2-1/2 weeks of his six-week course of treatment. Because the treatment revealed minimal constipation or nausea and increased energy levels, his intake of Decadron was lowered from 4 mg to 3mg. 13. On November 28, 2006, Mr. Doe finished the prescribed course of chemoradiation and the Temodar, Zofran and Bactrim treatment. Mr. Doe continued taking MiraLax a bit longer to treat persisting constipation. 14. On December 28, 2006, Mr. Doe expressed symptoms of pressure in his head when he lowered his Decadron from 4mg to 3 mg. He did not have any focal seizures or auras, had mild peripheral edema in his legs and stiffness in his hands – more so on the right- side than the left – difficulty breathing, and weight gain attributable to steroids. Overall, since being on Lasix and the stable dose of Decadron, Mr. Doe improved in his overall 15. A December 28, 2006 MRI, which is attached as “Attachment 3” revealed a clear
surgical cavity in the right temporoparietal region with a thin linear rim of enhancement. The gliadel wafer remnants were less prominent and the edema and mass effect 16. On or about January 25, 2007, Mr. Doe had a thallium Single Photon Emission Computed Tomography (SPECT) scan. It showed a moderate amount of blood flow activity in the brain and has since served as a baseline to assist in reviewing subsequent 17. On February 8, 2007, Mr. Doe’s next MRI, which is attached as “Attachment 4” showed
a small focal area of increased activity in the high right parietal region. 18. On March 1, 2007, another thallium scan was ordered to assess metabolic activity. Mr. Doe was also prescribed two additional cycles of Temodar at 350 mg per dose or 200 mg/m2. He tolerated the treatment well and was clinically stable. An updated March 16, 2007 MRI, which is attached as “Attachment 5” demonstrated clear evidence of further
tumor progression after the first two cycles of Temodar of the malignant glioma. Specifically, it showed increased nodular enhancement in the periphery of the surgical cavity. It also revealed further tumor progression in the right parietal region. INITIAL MARCH 2007 REQUEST FOR APPROVAL FOR AVASTIN/CPT-11 19. On March 20, 2007, because of the lack of response to the initial treatment and the rapid tumor growth, I sent Empire Blue Cross a letter requesting the approval for treatment with Avastin/CPT-11, a combination of a monoclonal antibody to Vascular Endothelial Cell Growth Factor Receptor (VEGFR) and active camptothecin. A copy of this letter is attached as “Attachment 6.”. The letter detailed the history of Mr. Doe’s condition and
the conventional treatments that he received. Duke University Medical Center now uses this regimen and the letter discusses Duke’s impressive results. 20. In March 2007, I spoke to Dr. John Boe, M.D., the Medical Director at Empire Blue Cross, urging him to consider the medical evidence and journal abstract I had submitted. Dr. Boe informed me that he could not consider the evidence until an appeal was pending and that Blue Cross would not make a coverage determination until treatment was commenced. He suggested that the involvement of a union representative might result in a prior-approval determination. Otherwise, he recommended that treatments begin and 21. Both the lack of the tumor’s response to the Temodar treatment and Empire Blue Cross’s initial denial for Avastin/CPT-11 prompted a need to move on to a new type of treatment: Carboplatin. Carboplatin is a third-line chemotherapy for his tumor type. Thalidomide is typically added to Carboplatin, but Empire Blue Cross denied coverage for Thalidomide, too. Empire Blue Cross did approve Mr. Doe for Celebrex, another agent with 22. At Mr. Doe’s next visit of March 28, 2007, he had gained weight and had limited energy: he was less active and fatigued easily with any amount of exertion. 23. On April 25, 2007, Mr. Doe completed his first cycle of single-agent Carboplaitin/Celebrex. He tolerated the dose without much difficulty and, aside from a mild drop in his platelet count at mid-cycle, he did not exhibit clinical problems. He continued to have trouble with weight gain, decreased energy and some shortness of breath on exertion because of his weight gain. At this point, I hoped that he would be helped by this conventional regimen because Empire Blue Cross had denied every other 24. On May 16, 2007, Mr. Doe had another MRI following two cycles of Carboplatin/Celebrex. Two days earlier, on May 14, 2007, he had a generalized convulsion from which he recovered well, but ever since, he had some difficulty with myopathy: continuous numbness in his left hand and fingers. He had to look at what he was picking up to be able to hold onto it with left hand, otherwise he very readily dropped things. He had occasional episodes of headaches and was notably cushingold. He also experienced progressive fatigue and suffered from shortness of breath with exertion because of his significant weight gain. 25. The MRI, which is attached as “Attachment 7,”showed an increased size in the surgical
cavity with some increase in the surrounding nodular enhancement and more prominent changes on the flair series. These findings go along with his level of symptoms and explain his breakthrough seizure activity. Further, these findings continue to indicate the very aggressive course that his tumor has been following since diagnosis. As a result, I had Mr. Doe’s morning Decadron dosage increased by 1mg. 26. In May 2007, I again consulted with Dr. Janet Foe, the neuro-oncologist at the Memorial Sloan-Kettering Cancer Center, who had evaluated Mr. Doe in September 2006. I also consulted with colleagues at Dana Farber Cancer Institute. Both felt that treatment with Avastin and CPT-11 was the most beneficial course of future treatment for Mr. Doe. Both concurred that Mr. Doe was not eligible for alternative clinical trials because of his MAY 23, 2007 REQUEST FOR APPROVAL OF AVASTIN/CPT-11 27. On May 23, 2007, NYOH’s financial department sent another letter to Empire Blue Cross requesting that they make a pre-determination regarding the Avastin/CPT-11. The letter again explained Mr. Doe suffered from highly aggressive right temperoparietal glioblastoma diagnosis, that his tumor and clinical symptoms had clearly worsened, and that he had been given a fair trial of conventional treatments. The letter also highlighted the impressive response rate obtained by researchers at Duke University Brain Tumor Center using the combination of Avastin/CPT-11 in patients like Mr. Doe. A copy of this letter is attached as “Attachment 8.”
28. No response was received from Empire Blue Cross that it would either approve or deny Mr. Doe’s treatment with Avastin/CPT-11. However, Empire Blue’s Medical Director advised that he could not look at any medical information unless a claim was submitted. He suggested that treatment begin and that a coverage claim then be submitted. 29. By the third week of June 2007, Mr. Doe had been experiencing progressive seizures, emergency room visits, falls, and left sided sensory symptoms. Clinical evidence showed his tumor to be aggressive. Against this background, Mr. Doe could not wait any longer. He urgently needed to begin alternative treatment to stave off the further progression of the disease. After consulting with me, Mr. Doe decided to commence treatment with Avastin/CPT-11. For over one month, he had waited for an insurance decision before starting treatment with Avastin/CPT-11. After the financial department attempt to write letter after letter, and after leaving several phone messages with supervisors at Empire Blue Cross on his behalf, some of which Empire Blue Cross responded to by requesting more time to review my May 20, 2007 letter, NYOH prepared TREATMENT WITH AVASTIN/CPT-11 STARTING IN JUNE 2007 30. On June 20, 2007, Mr. Doe had his first Avastin/CPT-11 chemotherapy for which he privately paid. He tolerated the first dose without much difficulty and had only minimal diarrhea for the first day. He had no difficulty with increased fatigue, and had no further seizures or auras. On July 5, 2007, he received the second treatment. 31. On July 25, 2007, Mr. Doe came for his second cycle (or third infusion) of Avastin/CPT- 11. His MRI, which is attached as “Attachment 9” revealed minimal, if any, change in
the enhanced series of the disease and no evidence of significant mass effect as compared to the pre-treatment MRI from May 16, 2007. Since the July 25, 2007 MRI was conducted over a month from the commencement of his treatment, it does not represent a true comparison baseline. The extent to which Mr. Doe’s tumor continued to grow following his May 2007 MRI, but prior to his commencement of Avastin/CPT-11 on June 32. On July 25, 2007, Mr. Doe felt much better, had no further seizures, had fewer sensory complaints in his left arm and hand, and reported a stronger left-hand grip. His blood counts were in order and his symptoms had somewhat improved. AUGUST 2, 2007 REQUEST FOR APPROVAL OF TREATMENT 33. On August 2, 2007, NYOH again submitted a claim requesting approval of the Avastin/CPT-11 treatment. The financial department explained that Dr. Janet Foe at Memorial Sloan-Kettering Cancer Center, who saw Mr. Doe in consultation after his second recurrence, recommended a trial of Avastin/CPT-11. Further, the financial department attached the abstract from the last ASCO meeting documenting the impressive response rate obtained by researchers at Duke University Brain Tumor Center using this combination of drugs in patients like Mr. Doe. A copy of NYOH’s August 2, 2007 request is attached as “Attachment 10.”.
34. In the first week of August, 2007, I finally received the Empire Blue Cross letter of July 30, 2007 denying approval of Avastin/CPT-11. This considerable delay forced Mr. Doe to commence treatment on a private pay basis, not knowing whether his necessary treatment costs would be covered by insurance. 35. Mr. Doe had undergone two treatments before Empire Blue Cross finally sent its denial, sixty-eight days after NYOH’s first letter, which was sent on May 23, 2007. STABALIZATION AND CLINICAL IMPROVEMENT WITH TREATMENT 36. On August 22, 2007, Mr. Doe completed his second cycle of Avastin/CPT-11. Clinically, he has not had any further seizures since he began the first cycle, two months ago. The function in his left side is significantly improved since the completion of the second cycle. He is now able to grip quite well with his left hand and has had minimal, if any, sensory changes in that side. He walks better and he has not fallen. 37. Mr. Doe has not had any adverse effects due to this treatment, such as fatigue, nausea, diarrhea, rash, or myelotoxicity. He has also been able to decrease his intake of 38. Mr. Doe’s most recent MRI from August 22, 2007 is attached as “Attachment 11.”
Significantly, compared to the July 25, 2007 MRI, the enhancing zones appeared stable or perhaps slightly smaller. Clearly, there was no progression. 39. On August 24, 2007, Dr. Janet Foe provided a follow-up second opinion on Mr. Doe, which is attached as “Attachment 12.” She noted that he is not a candidate for many
clinical trials because the placement of gliadel wafers is often an exclusion criteria. would strongly support the recommendation to give Mr. Doe Avastin in combination with CPT11. The published results in [Clinical Cancer Research] from January 2006 show that there is an excellent response rate and disease control seen with this combined therapy that far exceeds any other salvage therapy that is available for the treatment of glioblastoma. Further, “most patients have symptomatic benefit and many patient achieve durable control of periods as long as or longer as 6 months which really is quite remarkable for this disease.” This procedure is “very appropriate and … the best salvage treatment option if the patient does not have protocol based options available to them.” 41. Dr. Foe also noted that Mr. Doe has had “significant symptomatic and radiographic benefit from the combination of Avastin and CPT-11.” BASIS FOR CLINICAL OPINION TO PRESCRIBE CPT-11 and AVISTAN 42. My opinion to treat Mr. Doe with CPT-11 and Avastin is based on my years of clinical experience, my review of the medical finding in Mr. Doe’s case, his response to other types of chemotherapy treatment, consultation with other neuro-oncologists, including Dr. Foe, and the growing body of literature supporting its use. 43. I am aware that neither CPT-11 nor Avastin has yet to receive FDA approval for use with Mr. Doe’s specific type of cancer. However, off-label use is not uncommon in medical oncology when alternative treatments have not been successful. The decision to prescribe a drug for off-label use involves weighing the drug’s success in clinical trials with an individual patient’s circumstances. I feel that Mr. Doe has benefited both clinically and radiographically from this treatment, and would suspect that he would be given the same treatment at any other medical facility specializing in neuron-oncology. 44. In October of 1998, the Food and Drug Administration (FDA) approved Campostar for treatment of metastatic cancer, which has spread or recurred following treatment with standard chemotherapy. See Medicine on Line. FDA Approval of Colorectal Cancer Treatment – First to be Based on Survival Data. Available at: 45. Campostar has since been used to safely and effectively treat small cell and non-small cell lung carcinoma, refractory lymphoma and leukemia, and gynecologic cancer. Vassal G, Santos A, Deroussent, et al. Clinical Pharmacology of Irinotecan (CPT-11) in Accessed September 6, 2007; Hare CB, Elion G, Houghton P, et al. Therapeutic Efficacy of the Topoisomerase I Inhibitor 7-ethyl-10 (4- [1-piperdino]-1-piercino) Carbonyloxy-Camptothecin Against Pediatric and Adult Central Nervous System Tumor Xenographs. Cancer Chemother Pharmacol 1997; 39(3) 187-91; Cottu PH, Extra JM, Lerebours F, Espie M, Marty M. Clinical activity Ppectrum or Irinotecan. Bull Cancer 1998 Dec; Spec No:21-5; Shimizu Y, Umezawa S, Hasumi K. A phase II Study of Combined CPT-11 and Mitomycin-C in Platiuum Refractory Clear Cell and Mucinous Ovarian Carcinoma. Ann Acad Med Singapore 1988 Sep; 27(5):650- 6; Rosen LS. Irinotecan in Lymphoma,Leukemia, and Breast, Pancreatic, Ovarian, and Small-Cell Cancers. Oncology (Williston Park) 1988 Aug; 12(8 Suppl 6): 103-9. 46. Studies in the mid-to-late 1990’s tested the efficacy of CPT-11 against human tumor xenographs derived from adult and pediatric central nervous system malignancies and showed promising results. Jory V. CPT-11 For Brain Tumors. Available at: 47. Since October of 2003, Medicare has paid for Irinotecan treatment for glioma, including the malignant neoplasm of the parietal lobe. See Medicare Guidelines for off-label indications for Irinotecan, attached as Attachment 13.
BACKGROUND OF BEVACIZUMAB AND ITS USE TO TREAT OTHER CANCERS 48. Bevacizumab (Avastin) is another anti-cancer drug: an angiogenesis inhibitor (anti- angiogenic agent) which may limit a cancer tumor’s ability to form new blood vessels. Blood vessels supply tumors with the nutrients and oxygen they need to grow. Vascular Endothelial Growth Factor (VEGF) has been identified as one of the most potent proteins supporting both tumor growth and the development of new capillaries that provide a route for tumor cells to spread throughout the body. Avastin is an antibody that is designed to inhibit VEGF protein by binding to it. 49. The first trials to examine the efficacy of anti-angiogenic agents for cancer began in the 1990’s. In February 2004, the FDA approved the use of Avastin for the treatment of metastatic colorectal cancer based on trials showing it to effective when added to standard chemotherapy. See Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine 2004; 350:2335-42. Available at: http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlu s&list_uids=15175435. Accessed September 6, 2007. 50. Since 2004, Avastin has been investigated and used to effectively treat a number of other cancers, including: breast cancer; lung cancer: pancreatic cancer: and ovarian cancer. THE USE OF IRINOTECAN AND/OR BEVACIZUMAB TO TREAT RECURRENT 51. As set forth below, numerous studies have also shown Avastin and/or CPT-11 to be safe and effective for treating recurrent glioblastoma brain tumors. The journal articles and abstracts summarized below are not an all-inclusive list of all the studies done or 2007 RESULTS FROM MAMOUTH MEDICAL CENTER 52. Some of the most recent clinical results from treatment of recurrent glioblastoma with Bevacizumab and Irinotecan come from presentations at the 2007 American Society of 53. As reported in the June 2007 Supplement to the Journal of Clinical Onocology, from August 2005 to December 2006, physicians from Mamouth Medical Center assessed the overall responses, toxicity, cognitive function, and functional status in recurrent glioblastoma patients treated with this combination therapy. 54. They found that the combination of bevacizumab and irinotecan is well tolerated and safe. The overall response rate was 95.2% and significant improvements in cognitive and 55. A copy of the abstract outlining these findings is attached as “Attachment 14.”
2007 RESULTS FROM THE UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 56. Physicians from the University of Pittsburgh School of Medicine also presented at the 2007 ASCO Conference concerning their positive experience of treating patients with relapsed pre-treated malignant glioma with Bevacizumab plus Irinotecan therapy. 57. The objective response rate was 80%, with the median progression-free interval on 58. They concluded that this combination therapy was safe and had excellent activity even in this relapsed, heavily pretreated population of patients with high grade malignant glioma, most of whom would not be candidates for clinical trials. 59. An abstract of their findings is attached as “Attachment 15.”
60. Physicians from the Cleveland Clinic also recently presented at the 2007 American Society of Clinical Oncology concerning the progression free-survival-periods for glioma patients treated with Irinotecan and Bevacizumab. 61. The results of their study have been accepted by publication in the June 2007 Journal of Clinical Oncology. An abstract of their findings is attached as “Attachment 16”.
62. They found that this combination therapy improved six month progression-free survival 63. Clinical Cancer Research recently published the results of a promising study by physicians from the Duke Medical Center. See Vredenburgh JJ, Desjardins A, Herndon JE, et al., Phase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma, Clinical Cancer Res 2007 Feb; 13(4): 1253-1259. A copy of this peer-reviewed publication, along with the Duke team’s February 20, 2007 press release and 2006 abstract from its presentation at the 42nd Annual Meeting of the American Society of Clinical Oncology, is attached as “ Attachment 17,” hereto.
64. The Duke team noted that in 2005 the standard of care for the treatment of patients with glioblastoma was radiation therapy with concurrent temozolomide (Temodar) followed by six months of temozolomide. Studies today, show that this approach produced only 65. The Duke Phase II treatment results for patients with grade III-IV glioma, with Irinotecan and Bevacizumab, were excellent. Specifically, they produced objective evidence of radiographic response in 63% of the 32 patients who remained in the study. Further, of the 23 patients with grade IV gliomas, 1 patient had a complete response, 8 patients had stable disease, and 1 patient had disease progression as the best response. Tumor growth was halted up to twice as long as comparative therapies. 2007 RESULTS FROM THE UNIVERSITY OF TEXAS M D ANDERSON CANCER 66. Another study from February 2007 concluded that Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis in patients with malignant brain tumors by decreasing capillary leakage and associated brain edema. See Gonzalez J, Kumar AJ, Conrad CA, et. al., Effect of bevacizumab on radiation necrosis of the brain, Int J Radiat Oncol Biol Phys, 2007 Feb 1; 67 (2):323-6. A summary of this article is attached as “Attachment 18.”
2006 RESULTS FROM DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA 67. In April of 2006, Neurology published the results of a similar study of the effect of Bevacizumab and chemotherapy treatment on 14 patients with Grade III/IV malignant gliomas. MRI scans showed that contrast-enhancing tumors shrank in 7 patients, with reductions in as little as 2 weeks after initiation of therapy. Pope WB, Lai A, Nghiemphu P, et al., MRI in Patients with High-Grade Gliomas Treated with Bevacizumab and Chemotherapy, Neurology, 2006 Apr; 66: 1258 – 1260. A copy of this article and a press release with articles that subsequently cited this study is attached as “Attachment 19”.
2005 RESULTS FROM THE PRESBYTERIAN HOSPITAL (V. STARK-VANCE) 68. In May 2005, Dr. Virginia Stark Vance presented at the World Federation of Neuro- Oncology’s Second Quadrennial Meeting. She reported on her success in treating patients with relapsed malignant glioma with a combination of Bevacizumab and CPT- 11. Between March and December 2004, she treated 21 patients with this regimen. She found positive radiographic and/or clinical improvement in most of the patients. An abstract of her presentation and release by the Musella foundation are attached as “Attachment 20.”
2003 RESULTS FROM UCLA SCHOOL OF MEDICINE, UNIVERSITY OF TEXAS HEALTH CENTER, DUKE UNIVERSITY MEDICAL CENTER, AND THE 69. Physicians involved in two studies of Irinotecan (CPT-11) reported their findings in the May 2003 CANCER Supplement. See Cloughesy TF, Filka E, Kuhn J, et al., Two Studies Evaluating Irinotecan Treatment for Recurrent Malignant Glioma Using an Every-3-Week Regiment, Cancer 2003 May; 97(9 Suppl): 2381-6. A copy of this article is attached as “Attachment 21.”
70. The researchers confirmed the activity of CPT-11 in malignant glioma and found that the maximum tolerated dose for patients with recurrent malignant glioma was considerably 1999 RESULTS FROM DUKE MEDICAL SCHOOL, PHARMACIA AND UPJOHN; ST. JUDE’S CHILDREN’S RESEARCH HOSPITAL; AND UNIVERSITY OF CALIFORNIA 71. The physicians involved in this study assessed the activity, toxicity, and pharmacokinetics of CPT-11 in treatment of adults with recurrent malignant glioma. See Friedman HS, Petros WP, Friedman AH, et al., Irinotecan Therapy in Adults With Recurrent or Progressive Malignant Glioma. J. Clinical Oncol.1999 May; 17(5):1516- 25. A copy of this article is attached as “Attachment 22.”
72. They found that CPT-11 has activity in patients with recurrent glioma. Specifically, they found objective/partial responses in 15% of the 60 treated patients. Further, 33% of those treated received a best response of “stable disease;” and 30% treated had progressive disease. They also found that concurrent therapy with anti-convulsants and/or dexamethasone could enhance biliary excretion of CPT-11 and its metabolites. 73. While I understand that many coverage requests for off-label us of drugs, compassionate use of drugs, or entry into clinical trials are received by insurance companies each day, and that not all can be granted or are appropriate, the request for Avistan/CPT-11 in the setting of recurrent high grade glioma has become very common among neuro- oncologists across the country and is routinely approved by other insurance companies. It is medically inappropriate to deny this treatment for Mr. Doe. 74. Given Mr. Doe’s need for another course of treatment at the beginning of next week, which is treatment that Mr. Doe and his family cannot afford to privately pay, I request that an expedited decision be made on his appeal. I am available to discuss this appeal should any review doctors have any questions. 75. Thank you for your consideration of this meritorious appeal.

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