Proc. Natl. Acad. Sci. USA
Vol. 73, No. 10, pp. 3685-3689, October 1976 Medical Sciences
Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer* (vitamin C)
EWAN CAMERONt AND LINUS PAULINGI t Vale of Leven District General
Menlo Park, California 94025
Hospital, Loch Lomondside, G83 OUA, Scotland; and tt Linus Pauling Institute of Science and Medicine, 2700 Sand Hill Road,
Contributed by Linus Pauling, August 10, 1976
ABSTRACT Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplementa ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days) Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbatetreated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.
There is increasing awareness that the progress of human cancer is determined to some extent by the natural resistance of the patient to his disease. Consequently there is growing recognition that improvement in the management of these patients could come from the development of practical supportive measures specifically designed to enhance host resistance to malignant invasive growth. We have advanced arguments elsewhere indicating that one important factor in host resistance is the free availability of ascorbic acid (1-3). These arguments are based upon the demonstration that cancer patients have a much greater requirement for this substance than normal healthy individuals, on the realization that ascorbic acid metabolism can be implicated in a number of mechanisms known to be involved in host resistance, and finally, and most convincingly, on the published evidence that ascorbic acid can sometimes produce quite dramatic remissions in advanced human cancer (4, 5). In this communication we present the results of a clinical trial in which 100 terminal cancer patients received supplemental ascorbate as their only definitive form of treatment and compare their progress with that of 1000 matched patients managed by the same clinicians in the same hospital who did not receive any ascorbate supplementation or any other definitive form of specific anti-cancer treatment.
Protocol The study involved a treated group of 100 patients with terminal cancer of various kinds and a control group of 1000 untreated and matched patients. The treated group consists of 100 patients who began ascorbate treatment, as described by *
Publication no. 63 from the Linus Pauling Institute of Science and Medicine. This is part I of a series.
3685
Cameron and Campbell (4) (usually 10 g/day, by intravenous infusion for about 10 days and orally thereafter), at the time in the progress of their disease when in the considered opinion of at least two independent clinicians the continuance of any conventional form of treatment would offer no further benefit. Fifty of the treated subjects are those described in ref. 4 and the other 50 were obtained by random selection from the alphabetical index of ascorbate-treated patients in Vale of Leven District General Hospital, where treatment of some terminal cancer patients with ascorbate has been under clinical trial since November 1971. We believe that the ascorbate-treated patients represent a random selection of all of the terminal patients in this hospital, even though no formal randomization process was used. In the random selection three patients were excluded because supplemental ascorbate had been deliberately discontinued by order of another physician, and five were excluded because matching controls could not be found for them. Patients suspected or known to have voluntarily discontinued ascorbate treatment have been retained in the group, as have those who died from some cause other than their cancer. No patient was excluded because of short survival time. Eighteen patients, marked with a plus sign in Table 1, were still alive on 10 August 1976, 16 of them clinically "well." These 100 cancer patients, given ascorbate from the presentation date in their illness when their disease process was recognized to be "untreatable" by any conventional method, comprise the treated group. The control group was obtained by a random search of the case record index of similar patients treated by the same clinicians in Vale of Leven Hospital over the last 10 years. For each treated patient, 10 controls were found of the same sex, within 5 years of the same age, and who had suffered from cancer of the same primary organ and histological tumor type. These 1000 cancer patients comprise the control group. The detailed case records of these 1000 were then analyzed quite independently by Dr. Frances Meuli, M.B., Ch.B. (Otago, New Zealand), who established their presentation date of "untreatability" by such conventional standards as the establishment of inoperability at laparotomy, the abandonment of any definitive form of anti-cancer treatment, or the final date of admission for "terminal care." This presentation date of untreatability corresponds to the date when ascorbate supplementation was initiated in the treated group. Comparable survival times of the 10 matched controls could then be calculated. We accept that "the presentation date of untreatability" can be influenced by many factors in individual patients, but we contend that the use of 1000 controls managed by the same clinicians in the same hospital over the last 10 years provides a sound basis for this comparative study. We record our thanks to Dr. Meuli for her unbiased and valuable contribution to this investigation. Even though no formal process of randomization was carried
3686
Proc. Natl. Acad. Sci. USA 73 (1976)
Medical Sciences: Cameron and Pauling
Table 1. Comparison of time of survival of 100 cancer patients who received ascorbic acid and 1000 matched patients with no treatment8 Survival time (days)
Test
case/ Ten matched controls
Case Primary tumor no. type 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60.
Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Esophagus Esophagus Colon Colon Colon Colon Colon Colon Colon Colon Colon Colon Colon Rectum Rectum Rectum Rectum Rectum Rectum Rectum Ovary Ovary Ovary Ovary Ovary Breast Breast Breast Breast Breast Breast Breast Breast Breast Breast
mean
Test Sex Age F M F F M M M M M F M M M M M M F F M M M M M M M M F F F M M F F M F M F F F F M F M M M F F F F F F F F
F F F F F F F
61 69 62 66 42 79 76 54 62 69 45 57 74 74 66 52 48 64 70 78 71 70 39 70 70 72 80 76 58 49 69 70 68 50 74 66 76 56 56 75 56 57 68 54 59 49 68 49 67 56 56 57 53 66 68 53 75 74 49 50
Mean
Individuals 12 8 15 4 8 45 22 24 14 6 17 19 16 21 47 35 11 7 24 32 5 3 42 24 8 12 2 2 56 35 48 64 9 7 11 13 23 24 51 3 3 9 11 52 15 36 41 53 19 49 1 3 33 22 107 8 45 12 3 31
41 6 1 87 1 4 19 26 23 19 24 13 56 2 94 4 33 1 8 19 53 2 31 1 34 21 29 2 39 122 9 102 15 108 45 7 129 1 406 40 18 73 11 36 2 5 39 15 36 39 65 28 183 12 41 2 175 2 16 29
5 3 72 7 74 12 12 21 13 55 7 8 29 27 7 70 30 26 20 39 7 33 74 30 29 19
6 18 31 107 7 13 40 7 50 224 8 30 74 46 52 11 91 10 78 117 18 38 22 22 26 15 6 94 69 2 12 35 62 28
29 9 19 11 358 1 9 61 89 2 57 11 27 30 39 21 5 13 7 40 30 24 5 2 24 14 45 5 15 28 15 82 11 18 6 31 63 2 36 58 36 19 47 127 829 37 122 2 85 6 4 190 55 19 42 91 6 44 40
85 124 4 26 19 27 3 13 9 84 9 6 14 7 27 48 4 11 21 8 128 16 39 29 67 41 18 1 3 53 126 8 1 6 71 14 62 20 24 21 5 2 25 35 88 45 5 42 5 4 81 26 24 48 22 20 9 11 30 13 30 90 8 51 17 217 14 17 18 26 11 72 21 60 5 42 41 106 7 9 34 7 98 82 18 23 98 18 98 30 31 22 3 67 33 68 10 32 1 160 2 15 14 16 45 29 7 38 17 251 17 31 27 5 33 18 1 17 14 265
8 8 35 12 14 12 15 7 4 53 44 41 25 31 5 46 45 4 5 43 20 25 28 46 32 59 13 1 8 78 26 33 163 51 40 1 28 46 30 19 49 (184) 4 6 140 101 91 841 48 86 19 14 16 2 101 96 20 30 93 31
54 114 99 6 16 130 3 26 4 11 64 17 26 1 4 272 24 30 41 103 39 62 3 41 129 21 238 1 10 65 94 144 59 69 11 4 3 41 82 68 3 (97) 13 73 54 140 40 18 132 106 102 48 45 10 81 231 11 107 73 24
21 15 76 34 16 4 5 2 36 103 110 170 6 21 82 39 81 103 19 2 31 2 15 7 20 28 56 4 6 46 38 17 18 16 88 11 15 7 82 16 6
36 14 111 35 128 11 14 221 27 17 78 5 40 16 9 75 57 2 49 21 16 63 70 57 51 33 2 1 62 56 15 11 38
79
84 19
(32) 23 14 70 57 98 178
(13) (89) (47)
11 233 94 6 21 21 99 71 61
109 76 50 42 63 85 5 104
(14) 73 13 40 97 107 131 15 34 12 52 20 73 47 57 229
control case (%)
38.5 121 20.7 12 9 47.4 21.2 18 70.8 258 23.4 43 12.0 142 46.3 36 22.5 149+ 29.5 182+ 54.5 82 36.9 64 33.3 39 16.8 427 34.3 17 69.6 460 90 29.3 27.1 187 58 25.5 34.4 52 20.8 100 27.4 200+ 40.1 42 25.5 167 40.7 33 50 57.4 43 46.3 7.6 57 24.7 32 58.0 201 37.3 1267 52.5 144 170 38.5 33.8 428 31.8 157+ 38.8 58 123+ 43.8 861 25.5 62 100.6 44.4 223 22.2 18 223 70.9 38.1 140+ 198 45.0 759 67.2 64.8 226 33 35.5 183 124.9 240+ 41.9 123+ 75.4 4 43.8 22 21.8 69.0 576 102.8 342 78.8 567 49.1 86 74.2 590 8 37.5 35 37.1 82.6 1644+
314 58 19 85 368 184 1183 78 622 617 150 173 117 2542 50 661 307 690 227 151 481 730 105 655 81 87 93 750 130 347 4343 274 442 1266 494 149 281 3376 62 502 81 314 367 440 1129 349 93 146 573 163 9 101 835 333 720 175 795 21 94 1990
Medical Sciences: Cameron and Pauling
Proc. Natl. Acad. Sci. USA 73 (1976)
3687
Table 1. (Continued) Survival time (days)
Test
case/ Ten matched controls
Case Primary tumor no. type 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100.
Individuals
Sex Age
F 53 105 Breast 73 193 Bladder M 93 17 47 21 Bladder F 70 39 9 126 F 73 1 52 Bladder 23 F 77 3 52 Bladder 48 Bladder 6 9 M 44 36 Bladder 47 118 85 M 62 39 5 Bladder 66 M 69 F 71 7 8 Gallbladder 56 20 159 4 Gallbladder M 67 F 71 Kidney(Ca) 6 2 17 F 63 8 68 76 Kidney (Ca) F 51 16 82 27 Kidney (Ca) 7 15 7 Kidney(Ca) M 53 15 13 12 Kidney (Ca) M 55 Kidney (Ca) M 73 25 11 209 91 Kidney (Ca) M 45 35 19 Kidney(Pap) M 69 74 (24) 67 Kidney (Pap) 57 51 M 74 67 Lymphoma M 40 144 41 53 Lymphoma M 65 51 28 68 Prostate M 47 24 14 22 Uterus F 56 25 11 7 Chondrosarcoma M 63 20 25 3 1 "Brain" M 49 85 56 Pancreas 11 M 77 25 19 Pancreas M 67 112 6 55 F .60 Pancreas 11 42 23 F 54 Fibrosarcoma 13 1 171 Testicle 11 M 42 10 56 Pseudomyxoma M 47 35 16 1 F 68 Carcinoid 19 12 45 31 74 66 Leiomyosarcoma F 32 F 59 Leukemia 6 36 183 Stomach 34 34 M 55 12 F 51 128 Ovary 13 76 Bronchus 9-2 30 M 69 90 F 67 Bronchus 93 20 29 Colon 8 M 77 69 80 Colon 3 M 38 41 78
8 127 2 18 26 97 38 38 118 34 21 10 19 58 25 267 91 44 73 60 81 55 5 26 65 29 21 95 45 48 30 198 64 12 87b 43b (127) 324 16 20 117 138 101 53 130 126 136 17 57 24 91 78 256 25 57 69 30 64 39 102 (37) (27) 31 12 (28) (87) (121) 6 36 32 5 253 78 31 65 216 160 43 147 90 97 68 14 30 9 17 58 40
159 12 52 30 142 48 76 26 22 212 83 31 41 49 16 19 77 (37) (491) 29 56 23 67 17 (187) 38 36 49 10 46 19 8
Mean
Test
mean control
case
(%)
71 162 126 167 42 107.1 173+ 21 660 46 133 48 36.5 241 10 556 7 8 79 45.3 253 381 25 13 45 24 28.9 110 67 33 10 38 26 50.4 34 137 8 52 42 16 24.8 34 10 15 62.7 127 72 669+ 1067 53 85 12 13 27 56.5 30 64 30 22 47 14 34.1 22 91 275 94 31 209 16 76.0 14 114 60 106 176 327 53.8 241 8 69 29 49 36.9 89 8 125 (95) (117) 60.6 243 147 140 91 35 19 76 41.5 58 1562 89 95 6 83 42.2 659 31 7 293 30 50 480 61.0 5 127 74 82 61.5 3 34 49 21b 82b 14b 41b 49.0 24 918 174 126b 179b 97b 169.3 1554+ 41 279 302 103 102.8 1016+ 988 10 36 51 142 82 118 69.7 157 123 202 16 80 82.3 166+ 103 30 18 185 61 66.0 68 31 23 20 19 157 9 44.8 1 13 29 95 37 67 54.8 317 13 41 40 94 45.0 704 91 76 67 52 77.6 21 27 122 253 89 59 77.4 16 21 22 50 (101) (9) (25) (17) 44.1 17 (19) (29) (87) 41.6 15 36 (12) (15) (87) (162) 41.1 132 321 18 15 82 (38) 28.0 162+ 579 453+ [21] [44] [27] [242] 74.1 611 44 36 112 63 55.4 430+ 776 77 79 72 49 27 69.3 39 62 140 62 40 83.3 82 98 32 20 135 125 31 87.4 35 185 8 37 26 65.3 138 211 57 68 14 21 37.0 15 40 66 98 42 (80) 52.3 152+ 291
The sign + following the survival time of the patients treated with ascorbic acid means that the patient was alive on August 10, 1976. Parentheses () indicate that the matched patient had the same sex, same kind of tumor, and same dissemination, but had an age difference greater than 5 years. Brackets [] indicate opposite sex, same tumor, same dissemination, age difference greater than 5 years. For kidney, Ca indicates carcinoma, Pap, papilloma. b Diffuse urinary tract papillomatosis. The test cases (78 and 79) had lesions in both kidney and bladder. The nine control cases indicated had tumors of identical histology but their disease was confined to bladder mucosa. a
out in the selection of our two groups, we believe that they come close to representing random subpopulations of the population of terminal cancer patients in Vale of Leven Hospital. There is some internal evidence in the data in Table 1 to support this conclusion. A somewhat detailed description of the circumstances under which the study was made may be called for. Of the 375 beds in Vale of Leven Hospital, 100 are in the surgical unit, 50 in the medical unit, and 25 in the gynecological unit. The 100 beds in the surgical unit are in the administrative charge of Ewan Cameron, and 50 of them are in his complete clinical charge, the other 50 being in the charge of the second Consultant Sur-
geon of the Hospital. The two Consultant Surgeons are assisted by a changing group of four Surgical Registrars, who are qualified surgeons on assignment for terms of 6 or 12 months from one or another of the Glasgow teaching hospitals. They are assisted by residents and interns. Although some cancer patients are initially treated in the medical or gynecological unit, there is a tendency for cases of advanced cancer of all kinds
except leukemia and some rare childhood cancers, which are dealt with in a pediatric hospital in Glasgow, to gravitate into the surgical unit, in total probably 90% of all cases of cancer in the Loch Lomondside area. All of the patients are treated initially in a perfectly con-
Proc. Natl. Acad. Sci. USA 73 (1976)
Medical Sciences: Cameron and Pauling
3688
Table 2. Ratios of average survival times for ascorbate patients and matched controls, with statistical significance A
Bronchus (15) Colon (13) Stomach (13) Breast (11) Kidney (9) Bladder (7) Rectum (7) Ovary (6)Others (19) All (100)
B
C
(Days)
(Days)
136 282 98.9 367 333 196 226 148 172 209.6
38.5 37.0 37.9 64.0 64.0 43.6 55.5 71.0 56.8 50.4
D
3.53 7.61 2.61 5.75 5.21 4.49 4.10 2.08 3.03 4.16
E
-
G
(Days)
F (%)
(%)
47 59 43 91 88 57 71 78 67 65
47 54 46 55 67 57 86 83 53 60
8.7 20 17 22 22 20 33 30 27 25.7
H
I
24.5 7.63 6.41 5.74 8.35 4.90 7.57 6.83 5.28 55.02
Vol. 73, No. 10, pp. 3685-3689, October 1976 Medical Sciences
Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer* (vitamin C)
EWAN CAMERONt AND LINUS PAULINGI t Vale of Leven District General
Menlo Park, California 94025
Hospital, Loch Lomondside, G83 OUA, Scotland; and tt Linus Pauling Institute of Science and Medicine, 2700 Sand Hill Road,
Contributed by Linus Pauling, August 10, 1976
ABSTRACT Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplementa ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days) Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbatetreated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.
There is increasing awareness that the progress of human cancer is determined to some extent by the natural resistance of the patient to his disease. Consequently there is growing recognition that improvement in the management of these patients could come from the development of practical supportive measures specifically designed to enhance host resistance to malignant invasive growth. We have advanced arguments elsewhere indicating that one important factor in host resistance is the free availability of ascorbic acid (1-3). These arguments are based upon the demonstration that cancer patients have a much greater requirement for this substance than normal healthy individuals, on the realization that ascorbic acid metabolism can be implicated in a number of mechanisms known to be involved in host resistance, and finally, and most convincingly, on the published evidence that ascorbic acid can sometimes produce quite dramatic remissions in advanced human cancer (4, 5). In this communication we present the results of a clinical trial in which 100 terminal cancer patients received supplemental ascorbate as their only definitive form of treatment and compare their progress with that of 1000 matched patients managed by the same clinicians in the same hospital who did not receive any ascorbate supplementation or any other definitive form of specific anti-cancer treatment.
Protocol The study involved a treated group of 100 patients with terminal cancer of various kinds and a control group of 1000 untreated and matched patients. The treated group consists of 100 patients who began ascorbate treatment, as described by *
Publication no. 63 from the Linus Pauling Institute of Science and Medicine. This is part I of a series.
3685
Cameron and Campbell (4) (usually 10 g/day, by intravenous infusion for about 10 days and orally thereafter), at the time in the progress of their disease when in the considered opinion of at least two independent clinicians the continuance of any conventional form of treatment would offer no further benefit. Fifty of the treated subjects are those described in ref. 4 and the other 50 were obtained by random selection from the alphabetical index of ascorbate-treated patients in Vale of Leven District General Hospital, where treatment of some terminal cancer patients with ascorbate has been under clinical trial since November 1971. We believe that the ascorbate-treated patients represent a random selection of all of the terminal patients in this hospital, even though no formal randomization process was used. In the random selection three patients were excluded because supplemental ascorbate had been deliberately discontinued by order of another physician, and five were excluded because matching controls could not be found for them. Patients suspected or known to have voluntarily discontinued ascorbate treatment have been retained in the group, as have those who died from some cause other than their cancer. No patient was excluded because of short survival time. Eighteen patients, marked with a plus sign in Table 1, were still alive on 10 August 1976, 16 of them clinically "well." These 100 cancer patients, given ascorbate from the presentation date in their illness when their disease process was recognized to be "untreatable" by any conventional method, comprise the treated group. The control group was obtained by a random search of the case record index of similar patients treated by the same clinicians in Vale of Leven Hospital over the last 10 years. For each treated patient, 10 controls were found of the same sex, within 5 years of the same age, and who had suffered from cancer of the same primary organ and histological tumor type. These 1000 cancer patients comprise the control group. The detailed case records of these 1000 were then analyzed quite independently by Dr. Frances Meuli, M.B., Ch.B. (Otago, New Zealand), who established their presentation date of "untreatability" by such conventional standards as the establishment of inoperability at laparotomy, the abandonment of any definitive form of anti-cancer treatment, or the final date of admission for "terminal care." This presentation date of untreatability corresponds to the date when ascorbate supplementation was initiated in the treated group. Comparable survival times of the 10 matched controls could then be calculated. We accept that "the presentation date of untreatability" can be influenced by many factors in individual patients, but we contend that the use of 1000 controls managed by the same clinicians in the same hospital over the last 10 years provides a sound basis for this comparative study. We record our thanks to Dr. Meuli for her unbiased and valuable contribution to this investigation. Even though no formal process of randomization was carried
3686
Proc. Natl. Acad. Sci. USA 73 (1976)
Medical Sciences: Cameron and Pauling
Table 1. Comparison of time of survival of 100 cancer patients who received ascorbic acid and 1000 matched patients with no treatment8 Survival time (days)
Test
case/ Ten matched controls
Case Primary tumor no. type 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60.
Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Bronchus Esophagus Esophagus Colon Colon Colon Colon Colon Colon Colon Colon Colon Colon Colon Rectum Rectum Rectum Rectum Rectum Rectum Rectum Ovary Ovary Ovary Ovary Ovary Breast Breast Breast Breast Breast Breast Breast Breast Breast Breast
mean
Test Sex Age F M F F M M M M M F M M M M M M F F M M M M M M M M F F F M M F F M F M F F F F M F M M M F F F F F F F F
F F F F F F F
61 69 62 66 42 79 76 54 62 69 45 57 74 74 66 52 48 64 70 78 71 70 39 70 70 72 80 76 58 49 69 70 68 50 74 66 76 56 56 75 56 57 68 54 59 49 68 49 67 56 56 57 53 66 68 53 75 74 49 50
Mean
Individuals 12 8 15 4 8 45 22 24 14 6 17 19 16 21 47 35 11 7 24 32 5 3 42 24 8 12 2 2 56 35 48 64 9 7 11 13 23 24 51 3 3 9 11 52 15 36 41 53 19 49 1 3 33 22 107 8 45 12 3 31
41 6 1 87 1 4 19 26 23 19 24 13 56 2 94 4 33 1 8 19 53 2 31 1 34 21 29 2 39 122 9 102 15 108 45 7 129 1 406 40 18 73 11 36 2 5 39 15 36 39 65 28 183 12 41 2 175 2 16 29
5 3 72 7 74 12 12 21 13 55 7 8 29 27 7 70 30 26 20 39 7 33 74 30 29 19
6 18 31 107 7 13 40 7 50 224 8 30 74 46 52 11 91 10 78 117 18 38 22 22 26 15 6 94 69 2 12 35 62 28
29 9 19 11 358 1 9 61 89 2 57 11 27 30 39 21 5 13 7 40 30 24 5 2 24 14 45 5 15 28 15 82 11 18 6 31 63 2 36 58 36 19 47 127 829 37 122 2 85 6 4 190 55 19 42 91 6 44 40
85 124 4 26 19 27 3 13 9 84 9 6 14 7 27 48 4 11 21 8 128 16 39 29 67 41 18 1 3 53 126 8 1 6 71 14 62 20 24 21 5 2 25 35 88 45 5 42 5 4 81 26 24 48 22 20 9 11 30 13 30 90 8 51 17 217 14 17 18 26 11 72 21 60 5 42 41 106 7 9 34 7 98 82 18 23 98 18 98 30 31 22 3 67 33 68 10 32 1 160 2 15 14 16 45 29 7 38 17 251 17 31 27 5 33 18 1 17 14 265
8 8 35 12 14 12 15 7 4 53 44 41 25 31 5 46 45 4 5 43 20 25 28 46 32 59 13 1 8 78 26 33 163 51 40 1 28 46 30 19 49 (184) 4 6 140 101 91 841 48 86 19 14 16 2 101 96 20 30 93 31
54 114 99 6 16 130 3 26 4 11 64 17 26 1 4 272 24 30 41 103 39 62 3 41 129 21 238 1 10 65 94 144 59 69 11 4 3 41 82 68 3 (97) 13 73 54 140 40 18 132 106 102 48 45 10 81 231 11 107 73 24
21 15 76 34 16 4 5 2 36 103 110 170 6 21 82 39 81 103 19 2 31 2 15 7 20 28 56 4 6 46 38 17 18 16 88 11 15 7 82 16 6
36 14 111 35 128 11 14 221 27 17 78 5 40 16 9 75 57 2 49 21 16 63 70 57 51 33 2 1 62 56 15 11 38
79
84 19
(32) 23 14 70 57 98 178
(13) (89) (47)
11 233 94 6 21 21 99 71 61
109 76 50 42 63 85 5 104
(14) 73 13 40 97 107 131 15 34 12 52 20 73 47 57 229
control case (%)
38.5 121 20.7 12 9 47.4 21.2 18 70.8 258 23.4 43 12.0 142 46.3 36 22.5 149+ 29.5 182+ 54.5 82 36.9 64 33.3 39 16.8 427 34.3 17 69.6 460 90 29.3 27.1 187 58 25.5 34.4 52 20.8 100 27.4 200+ 40.1 42 25.5 167 40.7 33 50 57.4 43 46.3 7.6 57 24.7 32 58.0 201 37.3 1267 52.5 144 170 38.5 33.8 428 31.8 157+ 38.8 58 123+ 43.8 861 25.5 62 100.6 44.4 223 22.2 18 223 70.9 38.1 140+ 198 45.0 759 67.2 64.8 226 33 35.5 183 124.9 240+ 41.9 123+ 75.4 4 43.8 22 21.8 69.0 576 102.8 342 78.8 567 49.1 86 74.2 590 8 37.5 35 37.1 82.6 1644+
314 58 19 85 368 184 1183 78 622 617 150 173 117 2542 50 661 307 690 227 151 481 730 105 655 81 87 93 750 130 347 4343 274 442 1266 494 149 281 3376 62 502 81 314 367 440 1129 349 93 146 573 163 9 101 835 333 720 175 795 21 94 1990
Medical Sciences: Cameron and Pauling
Proc. Natl. Acad. Sci. USA 73 (1976)
3687
Table 1. (Continued) Survival time (days)
Test
case/ Ten matched controls
Case Primary tumor no. type 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100.
Individuals
Sex Age
F 53 105 Breast 73 193 Bladder M 93 17 47 21 Bladder F 70 39 9 126 F 73 1 52 Bladder 23 F 77 3 52 Bladder 48 Bladder 6 9 M 44 36 Bladder 47 118 85 M 62 39 5 Bladder 66 M 69 F 71 7 8 Gallbladder 56 20 159 4 Gallbladder M 67 F 71 Kidney(Ca) 6 2 17 F 63 8 68 76 Kidney (Ca) F 51 16 82 27 Kidney (Ca) 7 15 7 Kidney(Ca) M 53 15 13 12 Kidney (Ca) M 55 Kidney (Ca) M 73 25 11 209 91 Kidney (Ca) M 45 35 19 Kidney(Pap) M 69 74 (24) 67 Kidney (Pap) 57 51 M 74 67 Lymphoma M 40 144 41 53 Lymphoma M 65 51 28 68 Prostate M 47 24 14 22 Uterus F 56 25 11 7 Chondrosarcoma M 63 20 25 3 1 "Brain" M 49 85 56 Pancreas 11 M 77 25 19 Pancreas M 67 112 6 55 F .60 Pancreas 11 42 23 F 54 Fibrosarcoma 13 1 171 Testicle 11 M 42 10 56 Pseudomyxoma M 47 35 16 1 F 68 Carcinoid 19 12 45 31 74 66 Leiomyosarcoma F 32 F 59 Leukemia 6 36 183 Stomach 34 34 M 55 12 F 51 128 Ovary 13 76 Bronchus 9-2 30 M 69 90 F 67 Bronchus 93 20 29 Colon 8 M 77 69 80 Colon 3 M 38 41 78
8 127 2 18 26 97 38 38 118 34 21 10 19 58 25 267 91 44 73 60 81 55 5 26 65 29 21 95 45 48 30 198 64 12 87b 43b (127) 324 16 20 117 138 101 53 130 126 136 17 57 24 91 78 256 25 57 69 30 64 39 102 (37) (27) 31 12 (28) (87) (121) 6 36 32 5 253 78 31 65 216 160 43 147 90 97 68 14 30 9 17 58 40
159 12 52 30 142 48 76 26 22 212 83 31 41 49 16 19 77 (37) (491) 29 56 23 67 17 (187) 38 36 49 10 46 19 8
Mean
Test
mean control
case
(%)
71 162 126 167 42 107.1 173+ 21 660 46 133 48 36.5 241 10 556 7 8 79 45.3 253 381 25 13 45 24 28.9 110 67 33 10 38 26 50.4 34 137 8 52 42 16 24.8 34 10 15 62.7 127 72 669+ 1067 53 85 12 13 27 56.5 30 64 30 22 47 14 34.1 22 91 275 94 31 209 16 76.0 14 114 60 106 176 327 53.8 241 8 69 29 49 36.9 89 8 125 (95) (117) 60.6 243 147 140 91 35 19 76 41.5 58 1562 89 95 6 83 42.2 659 31 7 293 30 50 480 61.0 5 127 74 82 61.5 3 34 49 21b 82b 14b 41b 49.0 24 918 174 126b 179b 97b 169.3 1554+ 41 279 302 103 102.8 1016+ 988 10 36 51 142 82 118 69.7 157 123 202 16 80 82.3 166+ 103 30 18 185 61 66.0 68 31 23 20 19 157 9 44.8 1 13 29 95 37 67 54.8 317 13 41 40 94 45.0 704 91 76 67 52 77.6 21 27 122 253 89 59 77.4 16 21 22 50 (101) (9) (25) (17) 44.1 17 (19) (29) (87) 41.6 15 36 (12) (15) (87) (162) 41.1 132 321 18 15 82 (38) 28.0 162+ 579 453+ [21] [44] [27] [242] 74.1 611 44 36 112 63 55.4 430+ 776 77 79 72 49 27 69.3 39 62 140 62 40 83.3 82 98 32 20 135 125 31 87.4 35 185 8 37 26 65.3 138 211 57 68 14 21 37.0 15 40 66 98 42 (80) 52.3 152+ 291
The sign + following the survival time of the patients treated with ascorbic acid means that the patient was alive on August 10, 1976. Parentheses () indicate that the matched patient had the same sex, same kind of tumor, and same dissemination, but had an age difference greater than 5 years. Brackets [] indicate opposite sex, same tumor, same dissemination, age difference greater than 5 years. For kidney, Ca indicates carcinoma, Pap, papilloma. b Diffuse urinary tract papillomatosis. The test cases (78 and 79) had lesions in both kidney and bladder. The nine control cases indicated had tumors of identical histology but their disease was confined to bladder mucosa. a
out in the selection of our two groups, we believe that they come close to representing random subpopulations of the population of terminal cancer patients in Vale of Leven Hospital. There is some internal evidence in the data in Table 1 to support this conclusion. A somewhat detailed description of the circumstances under which the study was made may be called for. Of the 375 beds in Vale of Leven Hospital, 100 are in the surgical unit, 50 in the medical unit, and 25 in the gynecological unit. The 100 beds in the surgical unit are in the administrative charge of Ewan Cameron, and 50 of them are in his complete clinical charge, the other 50 being in the charge of the second Consultant Sur-
geon of the Hospital. The two Consultant Surgeons are assisted by a changing group of four Surgical Registrars, who are qualified surgeons on assignment for terms of 6 or 12 months from one or another of the Glasgow teaching hospitals. They are assisted by residents and interns. Although some cancer patients are initially treated in the medical or gynecological unit, there is a tendency for cases of advanced cancer of all kinds
except leukemia and some rare childhood cancers, which are dealt with in a pediatric hospital in Glasgow, to gravitate into the surgical unit, in total probably 90% of all cases of cancer in the Loch Lomondside area. All of the patients are treated initially in a perfectly con-
Proc. Natl. Acad. Sci. USA 73 (1976)
Medical Sciences: Cameron and Pauling
3688
Table 2. Ratios of average survival times for ascorbate patients and matched controls, with statistical significance A
Bronchus (15) Colon (13) Stomach (13) Breast (11) Kidney (9) Bladder (7) Rectum (7) Ovary (6)Others (19) All (100)
B
C
(Days)
(Days)
136 282 98.9 367 333 196 226 148 172 209.6
38.5 37.0 37.9 64.0 64.0 43.6 55.5 71.0 56.8 50.4
D
3.53 7.61 2.61 5.75 5.21 4.49 4.10 2.08 3.03 4.16
E
-
G
(Days)
F (%)
(%)
47 59 43 91 88 57 71 78 67 65
47 54 46 55 67 57 86 83 53 60
8.7 20 17 22 22 20 33 30 27 25.7
H
I
24.5 7.63 6.41 5.74 8.35 4.90 7.57 6.83 5.28 55.02
