CANCER GUIDE CONSULTATIONS - CASE HISTORIES Jeff Roth Jeff Roth was 28 when diagnosed with glioblastoma multiforme stage 4 brain tumor, the most aggressive brain tumor with an average survival of six to twelve months. Diagnosed July 1999. I worked a great deal with his father, Dennis, who coordinated Jeff's conventional and complementary care. Father and son had (and have) an excellent loving relationship, and while Jeff definitely followed Dennis's lead, Jeff has made independent decisions about what he did and did not wish to pursue. I met with Dennis in August 1999. Jeff had had surgery weeks earlier at Columbia-Presbyterian in NYC to remove the tumor, which was located in the left occipital lobe. He subsequently underwent external beam radiation treatments to the whole head, a total of 6000 rads. MRIs showed some residual tumor post-surgery, common for BT surgery. After surgery and radiation, Jeff suffered from an impairment of right-sided peripheral vision in both eyes, as well as significant cognitive deficits. The deficits included severely impaired short-term memory, the capacity to focus and concentrate, and aphasia. Neuropsychiatric evaluation confirmed a host of cognitive and learning impairments. When I first met with Dennis to consult on Jeff's case, I laid out a chart of levels of care, which I refer to as multi-tracking: conventional anti-tumor strategies, alternative anti-tumor strategies, complementary anti-tumor and host-defense building strategies. I explained that Dennis and Jeff could choose a primary anti-tumor strategy and then a whole range of complementary anti-tumor and host-building strategies all at the same time. The only significant conflicts might be between a mainstream anti-tumor strategy (i.e., chemotherapy) and an alternative anti-tumor system (i.e., Gonzalez metabolic, Burzynksi). We would also take care not to include any complementary treatments that might conflict with conventional treatments. Later, we developed a whole additional track: conventional off-label drugs that could be used together with Jeff's other treatments. In this vein, I recommended a series of steps: 1)Choose a top-flight neuro-oncologist to recommend chemotherapeutic or, if available, biologic therapies. See whether these treatments offer sufficient chance of response when comparing with alternative or other systems. I recommend Dr. Henry Friedman at Duke, who Dennis has heard of, and who I have found to be one of the most creative and aggressive neuro-oncologists for brain tumors. I also mentioned the drug Temozolomide (Temodol), which I had been familiar with from previous case, as a new agent with high therapeutic index: relatively good efficacy for BTs with low toxicity: taken orally with minimal side effects. I also mention the clincial potential of Tamoxifen for BTs. 2)Get a second opinion on whether further surgery is plausible and worth considering. I recommend Dr. Fred Epstein of Beth Israel Medical Center in NYC, a leading neurosurgeon who also embraces complementary care. 2)Investigate alternative approaches for BTs: I mention Burzynski and discuss his limited but promising data, as well as Nick Gonzalez's metabolic approach. While not recommending treatment (I never do) I suggest that we both compare data on chemotherapy with data on Burzynski. My first read on this comparison is that Burzynski data is rather preliminary, somewhat limited in scope, but intriguing, and that much more data from ongoing FDA-supported clinical trials may be needed to have a clearer sense of efficacy of antineoplastons in aggressive BTs. Gonzalez does not have data on BTs, but claims some therapeutic success. 3)Find a physician or specialist to coordinate complementary care. For someone in Jeff's situation, I recommend extensive and comprehensive complementary therapies which require the best possible oversight, both to be certain to get state-of-the-art approaches and to prevent negative interactions, either nutrient-nutrient, nutrient-herb, herb-herb, herb-drug, or nutrient-drug conflicts. As I often do, I recommend Keith Block, M.D. and his Block Medical Center in Evanston, Illinois, as the best complementary cancer physician. I discuss some of Block's approaches that I find promising: very low-fat diet with high vegetable, fruit, and grain intake, high intake of Omega-3 fatty acids, and supplements: soy isoflavones, flavonoids, antioxidants, amino acids, vitamins/minerals, a range of anti-tumor botanicals (curcumin, milk thistle, astragulus, many more), mushroom polysaccharides, alkylglycerols, etc. 4)I suggest that he also enlist the services of Mark Renneker, M.D., who does research on conventional and complementary cancer treatments for patients. Renneker often works with Block and he has an excellent track record of coming up with new approaches. 5)I refer Jeff to a psychotherapist, Dr. Ruth Bolletino of NYC, who treats cancer patients with an existential and mind-body approach, following closely the philosophy and approach of Lawrence LeShan, who trained her in cancer psychotherapy. Emphasis on cancer as a turnining point, meaning, purpose, psychological and spiritual self-realization. Dennis brings this plan to Jeff and they pursue every one of these approaches aggressively. Dr. Epstein does not recommend surgery at this time; may be worthwhile when/if Jeff has a recurrence. They decide to have Dr. Friedman coordinate conventional oncologic care: he recommends an aggressive multi-modal chemotherapy treatment plan including several months of Temodol, followed by several months of CCNU, then CPT-11 (Irinotecan), then one last round of Temodol. Through Fred Epstein, Jeff finds a New York oncologist, Dr. Joao Siffert of Beth Israel Hospital in New York, who will work with Dr. Friedman and implement this unusual chemotherapy protocol. Jeff proceeds with this course, receiving his chemotherapy treatments at Beth Israel. After slightly over one year of these shifting treatments he is put on Tamoxifen. With my assistance, and that of Keith Block and Mark Renneker, Dennis also pursues information on Gamma Knife radiotherapy, dendritic cell vaccines, off-label drugs, signal transduction inhibitors such as Gleevec, and other approaches. While many suggestions are put on the back burner (gamma knife, dendritic cell vaccines, Gleevec, Burzynski), Dennis and Jeff make contact with many specialists and it gives them both a greater sense that should Jeff's tumor recur, they would have potentially effective options This is a critical process for father and son (and the rest of the family), helping them sustain hope and a sense of control. Since mid-1999, Keith Block coordinates Jeff's complementary care and provides much needed consultation on his conventional options. Block puts Jeff on his low-fat diet (only animal product allowed is cold-water fish rich in omega-3s) and extensive supplementation as described above. Dennis also learned about the work of Jeanne Wallace, Ph.D., then of Santa Cruz, CA, who has developed an extensive nutritional intervention for brain tumor patients and has documented success in a "best case" series. Dennis consulted with Jeanne and worked out coordination between her and Dr. Block to arrive at the most efficacious diet/nutritional intervention program. The Block and Wallace programs largely overlap, but Wallace added several new agents: hypericin, berberine,and bromelain, among some other adjustments. Wallace also recommended a copper reduction regimen, starting with zinc piccolinate, later continued with an agent, tetrathiomolybdate (TM). (Copper reduction has been associated with anti-angiogenic activity). They also consulted Susan Silberstein, an educator and CancerGuide from Philadelphia who recommended a Chinese herbal combination, as well as a Chinese herbologist, George Wong of NYC, who gave them a combination tea for antitumor activity and side-effect reduction. Jeff has trouble tolerating Wong's tea. Jeanne Wallace also provided supplements (antioxidants, herbs, and amino acids such as glutamine, etc.) specifically geared to reduce chemotherapy side effects. Jeff experienced relatively few side effects from chemotherapy: he tolerated Temodol very well, and had absolutely no diarrhea on CPT-11, which usually causes very severe diarrhea. His CBCs were generally very good; no marked neutropenia or other cytopenias except when he was on CCNU. After his first CCNU treatment, his white blood cell count and platelets dropped markedly. Nupogen (G-CSF) was unsuccessful in raising his counts sufficiently to re-commence with chemotherapy. Jeff and Dennis decided to use the herbal chemo-support product recommended by Silberstein, as well as a Chinese herbal product called Nuturin that Dennis had discovered. Before using, they had these two formulas evaluated by four Chinese herbalists including Efram Korngold, all of whom approved. Three days later Jeff's WBC increased by 73% and his platelets rose comparably. Dennis recalls the physicians at Beth Israel asking, "What did you give him??" One week later, he commenced with CCNU again. Jeff continued taking the Chinese herbal support and had no further cytopenias. During the entire year of chemotherapy, Jeff vomited only twice. Jeff's primary team leaders are now Block, Renneker, and Wallace for complementary care, and Friedman for medical oncology, with my ongoing assistance. I found preclinical evidence that the Cox-2 inhibitor Celebrex might be useful for brain tumors, and Dennis and Jeff consulted their "team" who concurred. Jeff now takes Celebrex 200 mg 2x per day. Based on suggestion from Renneker and Block, Dennis and Jeff have also consulted Dr. Bernard Bihari of NYC who has used naltrexone, an immune modulator, with some success with cancer patients, including BT patients. Jeff has taken naltrexone since mid 2000. Jeff began therapy with Ruth Bolletino and has continued with her ever since; both patient and therapist report excellent progress. Jeff and Dennis have pursued many other mind-body spirit approaches: he went to a Reiki master I recommended, Pamela Miles, and did sound healing with oncologist Mitchell Gaynor, another recommendation. He practiced prayer; guided imagery; varieties of spiritual healing; energy healing with Ron Young in New York; acupuncture; acupressure; qi gong; Tibetan herbs (through a consult with Yeshi Donden, the Dalai Lama's physician); regional physical therapy (RPT); lymph drainage by a massage therapist; and the application of essential oils to the surgical scar on the back of his head by a highly regarded Chinese aromatherapist, Jeffrey Yuen. Some of Jeff's most powerful healing experiences occurred during meetings with a mystic Chasidic Rabbi from Paris, whose family had practiced spiritual healing for six centuries. Jeff sees him whenever he comes to the States, usually four times a year. Jeff has continued to have regular MRIs at 3 month intervals; he has also had SPECT and other imaging technologies to refine diagnostic information. Since June 1999, Jeff's MRIs have shown a focal area of residual tumor that may or may not be partially or entirely necrotic. There has been no evidence of progression whatsoever; one most recent scan arguably demonstrated a small degree of reduction. Two recent SPECT scans were both "cold" meaning no active tumor growth and no evidence of angiogenesis, or tumor blood vessel growth. Jeff's health has generally been excellent and he and his father have aggressively pursued approaches to improve cognitive functions. Jeff enrolled in a cognitive rehab educational program, and he consulted with Dr. Paul Harch of New Orleans, a specialist on hyperbaric oxygen (HBO). Jeff has had 40 HBO treatments and his cognitive improvements have been significant: his speech has dramatically improved and his short-term memory has also showed approximately nearly 90% improvement. In the past month, Dennis reports even more dramatic improvement: Jeff has returned to a fuller work schedule as his focus, concentration, and comprehension have gotten markedly better. The director of the school Jeff attends for cognitive rehabilitation called his father to say that he'd never seen a student improve so dramatically. Jeff and Dennis both feel that the HBO treatments played the most significant role in this recovery process. In their effort to remain vigilant, and in the hopes of reducing any residual tumor and reducing possibility of recurrence, Dennis and Jeff continue to seek mainstream and complementary therapies. Jeff completed chemotherapy one year ago, but he now has started a new round of Temodol and will take it for one week every three months for the next year, under Dr. Friedman's guidance. (Jeff's tumor had been analyzed for methylation with a test called MGNT. It was highly methylated, a sign that Temodol, a nitrosourea, is more likely to be effective.) He will also begin Iscador treatments this summer, to be admistered by Dr. John Forster of Philadelphia, and is commencing with an immune-stimulating Chickenpox virus vaccine protocol used in NYC by Dr. Raymond Chang, who I recommended to Dennis. When Jeff was first on Tamoxifen, his copper levels did not fall, despite treatment with the agent TM; Block found evidence that Tamoxifen was likely responsible. He was taken off Tamoxifen, but copper levels still did not reduce sufficiently for any therapeutic (anti-angiogenic) effect. TM was discontinued and Jeff was put back on Tamoxifen, a protein kinase C inhibitor with potential efficacy in BTs and relatively few side effects. He will continue with Tamoxifen while on his Temodol regimen. Over time, with particular help from Renneker, Dennis and Jeff have had samples of his tumor sent for analysis of various genetic markers and other molecular characteristics that will guide further experimental therapies, if they are needed. For example, they know that Jeff's tumor is positive for Epidermal Growth Factor Receptor (EGFR) expression; has damaged p53 suppressor genes, and expresses an oncogene called c-kit. Experimental therapies currently in the developmental pipeline may be right for Jeff given the knowledge they now possess. Today, Jeff remains stable and, and in a few months he will celebrate the three-year mark from initial diagnosis, which for glioblastoma multiforme is considered remarkable. He remains highly disciplined in sticking with the Block/Wallace diet and supplements and pursing psychospiritual healing. Jeff got married in August, 2000, in front of 350 jubilant family members and friends; I was honored to be present.