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Back to 1997 1st Quarter Table of Contents
Seventeen patients with mostly inoperable astrocytoma grade 3 or 4, received nutritional therapy and were compared to three groups of patients, being younger and more exposed to operation and irradiation. In spite of the higher abundance of negative prognostic factors, median survival of the nutritionally treated group was 18 months and ten days. After one year there were significantly more patients alive in this group, compared with the other three groups. This was a prospective research. Keywords: Astrocytoma 3 and/or 4; orthomolecular therapy/nutrition; clinical epidemiology; prospective. IntroductionAstrocytoma grades 3 or 4 are malignancies with a poor prognosis. Andersen found, after operation, a median survival of 4.5 months for astrocytoma grade 4; with supporting radiotherapy median survival was 7.5 months. The difference was statistically significant.1 In the same way Walker et al 2 and Kristiansen et al 3 found prolongation of life by postoperative radiotherapy with patients suffering from astrocytoma grades 3 or 4; they had mixed populations of both astrocytomas. Median survival with only surgery was respectively 3.5 and 5.2 months; with supporting radiotherapy median survival was respectively 8.7 and 10.8 months. Surgery alone has never been compared with mere symptomatic treatment (prednisone etc.). It is clear however, that surgery correlates with a better survival.2 Chemotherapy has very modest possibilities in these astrocytomas. Walker2 1. arts–bioloog Stadhouderslaan 30, 2517 HZ Den Haag found a median survival of 14 weeks with surgery alone. With BCNU (1.3-bis(2 chloroethyl)-1-nitrosourea) median survival was 18.5 weeks (the difference was statistically significant). When radiotherapy and BCNU-treatment were both applied, median survival was not significantly better than with radiotherapy as the only supporting treatment (median survival was respectively 35 and 34.5 weeks although average survival was best in the group that received radiotherapy and BCNU; but this was not statistically significant either). In a placebo controlled study, intravenously administered bleomycin did not potentiate the effect of supporting radiotherapy with patients suffering from astrocytoma grades 3 or 4.3 Shin et al4 found no significant prolongation of life when radiotherapy and misonidazole were compared with radiotherapy as the only supporting therapy. Prognostic factors are: a) Histological gradation: patients with astrocytoma grade 4 have a worse prognosis than patients with an astrocytoma grade 3.5 b) A low Karnofsky-index significantly correlates with a bad prognosis.2 c) Older people have, in general, a significantly worse prognosis than younger people.1,6 Andersen1 found that patients over 60 years old have a significantly worse prognosis than patients younger than 60. Yonoyama et al6 found that patients over 36 years old have a worse prognosis than patients under 36. However, Yonoyama also found that the group under 15 years old had a significantly worse prognosis compared with the rest of the sub-36 group and also when compared with the patients of over 36. So the group 16-35 years has the best prognosis. Although it is very likely that surgery prolongs life, the extent of surgery does not significantly influence survival.5 Duration of symptoms bears an inverse relationship to survival, which is especially significant for patients that had symptoms longer than six months before diagnosis. They lived significantly longer than the rest.6 Location is another important prognostic factor. None of the patients in the patient group of Yonoyama,6 with a deep or bilateral astrocytoma grade 3 or 4, survived after radiation therapy. In the same group, patients with a right-sided tumour had a more favourable prognosis than those with a left-sided tumour; the survival of these two groups was statistically different at two and three years after treatment. A right frontal location yielded a significantly better survival after two, three, four and five years compared with tumours located in the left frontal or in any other lobe. The favourable prognosis of the right-sided tumours is entirely attributable to the tumours located right frontally. Nutritional factors are very important in the prevention of cancer. More and more evidence is accumulating that most substances that prevent cancer also retard progression of existing cancer or even can cure it.7-10 With special reference to astrocytoma, extra vitamin C during pregnancy seems to reduce the risk of astrocytoma in the offspring.11 Much is unknown about possible therapeutic effects of nutrition. The following facts are interesting. The herb Pao Pareira inhibits, according to very recent research, the growth of an astrocytoma grade 3 in vitro up to 100 percent.12 Amygdalin (a form of vitamin B17) might cause regression in astrocytoma grade 3 and 4 according to Dutch and German physicians.13 Phenylacetate, a metabolite of phenylalanine, induces differentiation in gliosarcomas and this is at least one reason that phenylacetate prolongs life in rats implanted with this kind of tumour.14 Malignant glioma cells also differentiate in vitro, when phenylacetate is administered .15 Most nutrients discussed in references 7 to 10 have not been subjects of research in relation to astrocytomas. Nutritional support of patients with astrocytoma 3 or 4 is the subject of this study. Patients and Methods.The patient characteristics are summarized in Table 1(page 52). The Diet RecommendedThe diet recommended was based upon the so called Moerman-diet;16 many details are discussed in reference 7. The following main guidelines can be given: a) As much fruit and as many vegetables and/ or juices derived from these as possible. Especially citrus fruits, pineapple, carrots, broccoli and spinach were recommended. b) Brown rice and leguminous plants (later on especially soy products) are highly preferable over potatoes. c) Fat fish (not smoked) was advised three times a week. Herring, salmon, mackerel, tuna and seadevil were especially recommended. d)Leavened bread made from wheat and/ or rye without extra fat was recommended. e) Milk-products: only low fat milk-products, containing living lactobacilli, were permitted to a maximum of 0.5 litre a day. f) Cheese: only young cheese and no more than 40 grams daily. g) No meat h) Nuts and seeds: walnuts, almonds, pumpkinseed, sesameseed and linseed. Walnuts and almonds are preferred to other nuts, because of their high content of omega-3 fatty acids. Maize and peanuts were discouraged. i) Mushrooms: only Shiitake-mushrooms were recommended. j) Oils and fats: for heating, only olive oil was recommended. For salads linseed oil, Table 1: Characteristics of the patients; treatment refers to standard treatment; (10A and 10B are one patient).
soybean oil, walnut oil and/or pumpkinseed oil were recommended. The use of corn oil, sunflower oil and safflower oil was discouraged. Only a minimal amount of butter (on bread) was allowed. k) Herbs and spices: garlic, caraway seed, saffron, rosemary and curcuma were especially recommended. Parsley, ginger and capsicum were recommended to a lesser extent. Redundant salt was discouraged. l) Sugar: no (white) sugar; only minimal honey. m) Drinks: green tea and licorice tea were recommended; black tea was discouraged. One or two cups of regular coffee a day were allowed. The only alcohol allowed was several glasses of dry red wine a week. Nutritional SupplementationThe following lists the nutrient composition of multivitamin/mineral combinations used. A summary of the nutrients used by each patient is shown in Table 2a (page 53) and Table 2b (page 54). 1) Composition of Lamberts’ “One Daily” vitamins and minerals (per tablet) is as vitamin B1 25 mg (all minerals and trace elements are exvitamin B2 25 mg pressed in elemental values). niacin 100 mg vitamin B6 25 mg 2) Composition of “Dagravit 30 Totaal” folic acid 400 mcg per tablet is as follows: vitamin B12 10.0 mcg vitamin A 0.3 mg biotin 0.15 mg vitamin B1 1.5 mg pantothenic acid 50 mg vitamin B2 1.5 mg choline 25 mg vitamin B6 0.5 mg inositol 25 mg vitamin B12 0.5 mcg PABA 25 mg niacin 10 mg dicalcium phosphate 75 mg calcium d-pantothenate 1.5 mg ferro fumarate 10 mg biotin 12.5 mcg zinc gluconate 15 mg PABA 10 mg potassium iodide 150 mcg vitamin C 20 mg manganese gluconate 5 mg vitamin D3 10 mcg copper gluconate 2 mg vitamin E 1 mg molybdate 500 mcg rutin 2.5 mg selenol-methionine 200 mcg iron 15 mg chromium (AA chelate) 200 mcg calciumphosphate 250 mg
Table 2a. Nutritional Supplementation of the Patient Group.
potassium magnesium copper manganese zinc iodine molybdenum fluoride nickel selenium 5 mg 5 mg 0.5 mg 0.5 mg 0.5 mg 50 mcg 50 mcg 50 mcg 50 mcg 50 mcg Nutrients in these multivitamins are not added to the amount of the individual nutrients, given separately or in other combinations: 3) Glutathione-complex 500 mg consists of: l-glutathione 50 mg l-glutamic acid 194 mg l-cysteine 158 mg glycine 98 mg. 4) Ferriaromatica-triplex was a solution with sucrose and Fe 3+ originally prescribed by the late physician, Moerman.17 5) SFB-complex contains per tablet: coenzyme Q10 5 mg thioctic acid 10 mg vitamin E 100 mg pyridoxal-5-phosphate 10 mg vitamin B1 10 mg riboflavin (active form) 4 mg niacin 40 mg pantothenic acid 150 mg magnesium citrate 210 mg 6) Polyerga is derived from embryonal Kupffer-cells of the liver.17 7) Iscador is an extract of the mistletoe.18 8) Venalot contains 15 mg coumarin and 90 mg troxerutin per tablet. 9) Pao Pareira specific extract (pareirine), is derived from the inner bark of a tropical tree.19 Table 2b. Nutritional Supplementation of the Patient Group.
Results and Discussion.The results are summarized in Table 3. Patient no. 3 developed a hemiplegia in spite of his corticosteroids and the canula. After the introduction of amygdalin the hemiplegia disappeared; the intake of the corticosteroids could be lowered and the regression was confirmed by a CT-scan. Patient 15 had an astrocytoma grade 3 of the brain stem. A decompression operation was only possible, followed by radiation treatment. His situation then slightly improved. Six months later, when he came under my treatment, he was still in a wheelchair. After half a year under my treatment he was somewhat better. Later on (between 9 and 20 months after radiation treatment) he continued to improve; he did not need the wheelchair any longer and was able to resume work. Two years after diagnosis his situation deteriorated and he died a few months later. It is clear that the regression of the tumour of patient no. 3 is not attributable to anything else but amygdalin. In the case of patient no. 15 it is unlikely that the regression was due to a late effect of radiation treatment, because at first there was only some improvement of the situation, while the regression that I saw occurred a relatively long time after the decompression operation and radiation treatment. A spontaneous regression is not a likely explanation, because it has been seen only once in the case of a patient with an astrocytoma grade 3, which was partly operable. An infection caused a regression of the remaining tumour, after 18 months there was a relapse.20
Patient no. 3 had an astrocytoma grade 4 and patient 15 had a brain stem astrocytoma grade 3; both were inoperable and during the clinical course there were no infections. So especially these two patients were very remarkable. Moerman himself treated with a less extensive but comparable regime of diet and supplements, a ten-year old boy who suffered from a relapse of an astrocytoma grade 4, which had been treated 3 months earlier with operation and radiation treatment. The boy recovered and almost 25 years later he is still in good health.16 The average age of the patient group at diagnosis was 40.5 years; median age was 37 years. Compared with research on similar patients in hospitals in Europe, the U.S.A. and Australia, our patients are, on average, younger. The average age of the patients in the references 1, 2, 3, 21, 22, 23, 24 and 25 is respectively >40 (only grade 4), 58, 55, 58, >50, >50, 48 and 52. The average age in two studies from Japan6 and Taiwan26 was respectively 35.4 and 38.4 years. In the Taiwan study pilocytic astro-cytomas and older patients were excluded. In my research the average age would not change if the 2 pilocytic astrocytomas had been excluded. In the Taiwan study the average age would have been lower if the pilocytic astrocytomas had been included. The Japanese study suggests that Japanese patients with astrocytomas grade 3 or 4 are younger than patients with the same disease in the Western world. These facts also suggest that younger patients with an astrocytoma grade three or four are more likely to enter an “alternative” (orthomolecular) practice than older patients with one of these astrocytomas; at least in the West. What is far more interesting is survival. Median survival was 18 months and ten days. Excluding the two pylocytic astrocytomas, median survival was 13 months. Table 4 shows survival for the whole group, the grade 4 subgroup and the grade 3 subgroup with and without the 2 pilocytic grade 3 astrocytomas. It is remarkable that the patients in this pilot study have a significantly better survival than any group of similar patients already mentioned in references. This means that I only aim at a comparison with groups for which no preselection was made and in which no chemotherapy was applied. Secondary references confirm this picture. Look for example at the table in reference 6, page 489. In the introduction it has been made clear that age is an important prognostic factor. However, not everyone thinks this way,25 perhaps because people over 50 usually have a worse prognosis.23 It is also true that grade 4 tumours are relatively more Table 4. Long-term Survival of Patients by Grading.
frequent at older ages.27 Therefore we decided to conduct a statistical comparison between our group and three (sub)groups from literature, having a lower average age than our group. We found three such groups. First Yonoyama et al 6 Chisquare testing28 shows a significantly better one year survival (82% versus 52%); the group of Yonoyama et al consisted of 127 persons; survival is significantly better in our group(P<0.05). Two and three year survivals are not significantly different. This result is solid, because people in the group of Yonoyama et al were on the average younger, more often operated upon, more often given radiation treatment and there were fewer brain stem astrocytomas in their group. The second group is Dutch,25 consisting of 25 patients with ages between 17 and 39; 16 had grade 3 and 9 had grade 4. Of the grade 3 patients 8 had not been treated with radiation; their median survival was less than one month. The grade 3 patients given radiation treatment had a median survival of 17.5 months. The grade 4 patients, who had not been given radiation treatment (4 pts) had a median survival of less than one month; while those who (5 pts) had been given radiation treatment, had a median survival of 8.9 months. A higher average percentage of this group than in ours had been operated upon (respectively 89 and 47 per cent). We now will compare our group only to the grade 3 and 4 patients who had been given radiation treatment. First we adjust the high level of grade 3 tumours in this group; on the basis of the median survivals it is easy to find that their total median survival would have been 12.5 months if the relative numbers of grade 3 and 4 in that group had been equal to ours. A chisquare test to establish the odds of being alive after 12.5 months shows that significantly more patients were alive in our group (11 in our group and 6.5 in the other; P<0.05). The third group to be compared with, is a subgroup of North et al.22 This is a subgroup of 39 patients, who were all younger than 40; 67% of them had been operated upon (versus 47% in our group) and 82% had been given radiation treatment, while this was 94% in our group. Biopsy and radiotherapy were also found to be slightly less effective than mere surgery (Table 4, page 56). After one year, 23 of the 39 patients of the group referred to were alive. This is (according to a chisquare test) significantly less than in our group (P< 0.05). So the main conclusion is that our group, in spite of having a poorer prognosis on the basis of partly interrelated risk factors, had a significantly better life expectancy. Taking the three groups together and comparing this with our group, expresses the difference even more significantly. Average survival after three years is only known for the groups of Yonoyama et al and North et al, and is slightly higher in the group of North et al and lower in the group of Yonoyama et al. Altogether three year survival is non-significantly better in our group. AcknowledgementsI am grateful to the Foundation for Orthomolecular Medicine (S.O.E., The Hague, The Netherlands) for critically reading the manuscript. References.
tiple Daily Fractionated Radiation therapy and Misonidazole in the Management of Malignant Astrocytoma; a Preliminary Report. Cancer 1985; 56: 758-760. 5. Urtasun RC, Cosmatos D, Delrowe J, et al: Iododeoxyuridine (IUdR) Combined with Radiation in the Treatment of Malignant Glioma: a Comparison of Short Versus Long Intravenous Dose Schedules (RTOG 86-12). Int J Radiat Oncol Biol Phys 1993; 27: 207- 214.
11: 1216-1222. 10.Wakui A, et al: Randomized Study of Lentinan on Patients with Advanced Gastric and Colorectal Cancer; Gan To Kagaku Ryoho 1986; 13: 1050-1059. 11.Preston-Martin S, Mack W and Henderson BE: Risk Factors for Gliomas and Meningiomas in Males in Los Angeles County; Cancer Research 1989; 49: 6137- 6143. 12.MS Distri-Pharma SA Group: PB-100: A Potent and Selective Inhibitor of Human BCNU Resistant Glioblastoma Cell Multiplication. Anticancer Research 13: 2301-2308. 13.Personal Communication: Landman JRG, physician, Acacialaan 12; 3481 XS, Harmelen, Holland. 14.Ram Z, Samid D, Walbridge S, et al: Growth Inhibition, Tumour Maturation, and Extended Survival in Experimental Brain Tumours in Rats treated with Phenylacetate; Cancer Research 1994; 54: 2923-2927. 15.Samid D, Ram Z, Hudgins W et al: Selective Activity of Phenylacetate Against Malignant Gliomas: Resemblance to Fetal Brain Damage in Phenylketonuria; Cancer Research 1993; 54: 891-895. 16.Antonczyk A, Valstar E and Wiese J: Retrospectief onderzoek naar de effectiviteit van de Moermantherapie bij kankerpatiënten; SDU Den Haag; 1991; 33-35. 17.Moerman C: Kanker kan genezen door dieet en therapie Ankh Hermes BV; Deventer, 1979. 18.Weleda AG: Directions for the Use of Iscador. Weleda AG, Stollenrain 11, Ch-4144 Arlesheim/Bl; Switzerland; 1986. 19.Beljanski M: Cancer Therapy: a New Approach. Deut Zeit für Onkologie 1990; 22: 145-152. 20. Margolis J and West D: Spontaneous Regression of Malignant Disease: Report of Three Cases. J Amer Geriatr Soc 1967; 15: 251. 21.Victor S and Lausberg G: Das maligne Hirngliom - eine katamnestische Studie über 100 operierte Patienten. Zent bl Neurochir 1991; 52: 59-68. 22.North B, Reilly P, Blumbergs P, et al: Malignant Astrocytoma in South Australia: Treatment and Case Survival; Med J Australia 1990;153: 250-25. 23.Frankel SA and German WJ: Glioblastoma Multiforme: Review of 219 Cases with Regard to Natural History, Pathology, Diagnostic Methods and Treatment. J Neurosurg 1958; 15: 489-503. 24.Roth JG and Elvidge AR: Glioblastoma Multiforme: a Clinical Survey: J Neurosurg 1960; 17: 736-750. 25.Rutten EHJM, van Daal WAJ, Slooff JL, et al: Postoperatieve bestraling bij astrocytoom 3 en 4. NTvG 1991; 135: 1131-1134. 26.Wang HC and Ho YS: Clinicopathological Evaluation of 78 Astrocytomas in Taiwan with Emphasis on a Simple Grading System; J NeuroOncol 1992; 13: 265- 276. 27. Kin TS, Halliday AL, Hedley TS, et al: Correlates of survival and the Daumas-Duport Grading System for Astrocytomas; J Neurosurg 1991; 74: 27-37. 28.Wijvekate ML: Verklarende statistiek; Het Spectrum Utrecht. 1973. | |||||||||||||||||
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