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[Pathology]

Supplemental Ascorbate in the Supportive Treatment of Cancer:

1. Prolongation of Survival Times in Terminal Human Cancer *

(vitamin C, ascorbic acid)

EWAN CAMERON and LINUS PAULING

Vale of Leven District General Hospital, Loch Lomondside, G83 QUA,
Scotland

and

Linus Pauling Institute of Science and Medicine, 2700 Sand Hill Road,
Menlo Park, California 94025, U.S.A.

Contributed by Linus Pauling 1976

*Publication no. from the Linus Pauling Institute of Science and Medicine
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 change (in cancer)
indicates a substantially increased requirement and utilization of this
substance to energize 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 supplemental ascorbate. The
mean survival time is 4.06 times as great for the ascorbate subjects
(204 days) as for the controls (50 days).

The results clearly indicate that this simple and safe form of
medication is of definite value in the treatment of patients with advanced

cancer.
The nature of the study

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.
(No patients with lung cancer were included; they are treated in another
hospital. ) | The treated group consists of 100 patients who began

ascorbate treatment, as described by Cameron and Campbell* (usually

10 g per 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.

(There is one exception, Case 80, who is Case 45 of Ref. 4 and the

subject of Ref. 5. As is explained in these papers, he was started on

the ascorbate treatment while waiting for high-energy radiation therapy,

and has received no treatment other than ascorbate.) Fifty of the treated

subjects are those described in Ref. 4 (with, however, different case

numbers) and the other fifty 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 had been begun in 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.

Four of the treated patients (Cases 17, 59, 80, and 84) were in Hairmyres

Hospital; they are included because they had been included in the group

described in Ref. 4, and it seemed unwise to us to omit them. In the
random selection three patients were excluded because supplemental
ascorbate treatment had been discontinued by order of another
physician and five were excluded because matching controls could not
be found for them. Patients 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. The survival times of the 19 patients

marked with a star coxvespond to the date 10 July 1976, on which they
were still alive.

Ten control cases for each treated case were selected by random
search of the index for the last ten years in Vale of Leven Hospital.
All ten control cases match the treated case as to kind of cancer, sex,
and age of the patient (to within five years). The case of pseudomyxoma
(91) was difficult to match, requiring search of the records for 20 years;
this case was included, despite this difficulty, because of its inclusion in
Ref. 4. Selection of the 1000 control cases was made by Frances Meuli,
M.B., Ch.B. (Otago), who was given the sex and age of the patient and
the type of cancer for each of the 100 treated cases, but who had no
knowledge of their survival times. She determined from the records
the date at which each control patient was classified as untreatable, from
the establishment of inoperability at laparotomy, the abandonment of any
definite form of cancer treatment, or the final date of admission for

"terminal care."' We thank Dr. Meuli for her valuable contribution to
this investigation.

Even though no formal process of randomization was carried 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.
The Results of the Study
The results of the study are given in Table 1 and summarized in
Table 2, in which values for different kinds of cancer represented by
7 or more patients treated with ascorbate (70 or more controls) are shown.
For each of the eight categories the ratio of average days of survival
(ascorbate/controls) is greater than unity, the range for the eight categories
being from 2.5 to 7.4, with 4.06 for all 100 patients. The ratios are
somewhat uncertain; for example, omitting the patient with longest
survival in the colon group would decrease the ratio from 7.4 to 5.2. At
the present time we cannot conclude that ascorbate has less value for one
kind of cancer than for others. Our conclusion is that the administration
of ascorbic acid in amount about 10 g per day to patients with advanced
cancer leads to about a four-fold increase in their life expectancy, in
addition to an apparent improvement in the quality of life. This great
increase in survival time results from the much larger numbers of the
ascorbate patients than of the controls who live for long times, as is

shown in Figure 1. Sixteen percent of the patients treated with ascorbic
acid survived for more than a year, fifty times the value for the
controls (0. 3%).

Statistical analysis shows that the null hypothesis that the treatment
with ascorbate has no benefit is to be rejected for each of the categories
in Table 2. The results of a simple statistical test are given in the table.
A reasonable dividing line, the average survival time for all subjects, is
given in column E, and the percentages exceeding this value are given in
columns F and G. Column H contains the values of x? obtained by a
two-by-two calculation, and I gives the corresponding values of P (one-
tailed). Similar values are obtained by non-parametric methods.

The fraction of survivors at time t after the initial date (determination
of nontreatability) is given to within +0.01 by the expression exp(-at), in
which t is the survival time in days and a has the value 0.021d7!. This
expression corresponds to a constant mortality rate for this group of
untreated patients with terminal cancer, and its validity suggests that for
them a single random process, occurring with a probability independent of
time, leads to death. For the group of patients treated with ascorbate the
same expression with a about 0.007 qv} approximates the fraction of
survivors up to about 100 days, after which a larger fraction of survivors
is found, reaching about 0.07 beyond 600 days. A simple interpretation of
these facts is that the administration of ascorbate to the patients with
terminal cancer has two effects. First, it increases the effectiveness of

the natural mechanisms of resistance to such an extent as to lead to an
increase by 3 in the average survival time for all patients; 3 is the ratio

of the two values of a, 0.021 and 0.007. Second, it has another effect

on about 7 percent of the patients, such as to cause them to live a much

longer time. This effect might be such as to "cure” them; that is, to -

give them the life expectancy that they would have had if they had not
developed cancer. On the other hand, it might only set them back one or

more stages in the development of the cancer, in which case their life
expectancy would be somewhat less than that corresponding to complete
elimination of the effect of their having developed cancer. This uncertainty
may be eliminated in the course of time, as the survival times of the 19
patients in the ascorbate-treated group who were still living in 10 July 1976
become known.

Conclusion -

In this study the times of survival of 100 ascorbate-treated cancer patients

in Scotland (measured from the day when the patient was pronounced to have
cancer untreatable by conventional methods) have been discussed in comparison
with those of 1000 matched controls, 10 for each of the ascorbate -treated
patients. The data indicate that deaths occur for about 93 percent of the
ascorbate -treated patients at one third the rate for the controls, so that for
this fraction there is a threefold increase in survival time, measured from
the date when the cancer was pronounced untreatable. For the other 7 percent
of the ascorbate-treated patients the survival time is not known with certainty,
but it is indicated by the values in Table 1 to be more than 22 times the

average for the untreated patients. The value 4.06 (Table 2) for the ratio
of average survival times expresses the resultant of these two effects
(note that 93 percent of 3 plus 7 percent of 22 equals 4. 33).

We conclude that there is strong evidence that treatment of
Scottish patients with terminal (untreatable) cancer with about 10 g of
ascorbate (ascorbic acid, vitamin C) per day increases the survival time
by the factor 3 for most of them and by at least 22 for a few (about 7 percent).
It is our opinion that a similar effect would be found for untreatable cancer
patients in other countries. Larger amounts than 10 g per day might have a
greater effect. Moreover, we surmise that the addition of ascorbate to the
treatment of patients with cancer at an earlier stage of development might
well have a similar effect, changing life expectancy after the stage when
ascorbate treatment is begun from, for example, five years to twenty years.

We have begun studies along this line.

This study was supported by research grants from The Secretary of

State for Scotland and The Educational Foundation of America.
10,

References

Cameron, E. & Pauling, L. (1973) "Ascorbic acid and the glycosamino-
glycans: An orthomolecular approach to cancer and other diseases",
Oncology 27, 181-192.

Cameron E. & Pauling, L. (1974) "The orthomolecular treatment of
cancer.I, The role of ascorbic acid in host resistance", Chem. -Biol.
Interactions 9, 273-283.

Cameron, E. (in press) "Biological function of ascorbic acid and the
pathogenesis of scurvy: a working hypothesis", Medical Hypotheses.
Cameron, E. & Campbell, A. (1974) "The orthomolecular treatment of
cancer, II. Clinical trial of high-dose ascorbic acid supplements in

advanced human cancer",Chem. -Biol. Interactions 9, 285-315.

 

Cameron, E., Campbell, A., & Jack, T. (1975) "The orthomolecular
treatment of cancer, III. Reticulum cell sarcoma: double complete
regression induced by high-dose ascorbic acid therapy", Chem. -Biol.

Interactions 11, 387-393.
Table 1

Comparison of time of survival of 100 cancer patients who received

ascorbic acid and 1000 matched patients with no treatment *

 

 

 

Primary . Tesi
Case ‘Tumor Survival time. (days) Test casi
No. Type Sex Age Ten matched controls © Mean case mea

1. STOMACH =F 61 12 41. 5..29 85 124 8 S4 22 36] 38.5 12h 314%
2. STOMACH M 69 8 6 3 9 4° 26- 8 114 15 14] 20.7 12 S88>
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4. STOMACH. F 66 4 87 7 J 3 “130 °412~«6 84S 24.2 18 0 By 8
S. STOMACH . M 42 8 1 74 358 9 84 14 16° 16 128] 70.8 258 368%
6. STOMACH M 79 45 4 12 2 9 6 12 130 4 | 23.4° 43 lef
7. STOMACH M76 22 19 #12 #9 14 #7 15 3 5S (14 | 12.0. 142 1183.8
8. STOMACH M S4 24 26 ‘21 61°27 #48 «+7 «#42 2 221} 46.3 fe 78%
9. STOMACH M 62 14°23 13 89 4 Uy 4 4 36 27 22.5 119+ 52B%
jo, srommcH =F 69 | ©6119 55-2 AL BSB UL 103.17 | 29.5 eRe HEY.

 

 
 

 

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1. STOMACH M 45 17-24 ° 7) 87-128 :«=«160 44. 64 110, 78 54.5 82 150%
2. sToMacH M57 19 13 8 I 39 29% 42 17 170 ,5 | 36.9 64° 1738
3, proncaug M 74 ‘| 16 56 29 "27° 67 41 25 26 6 40 | 33.3 39 1I78
4. sroncnus M 74 | 21 2 -27. 30 18 "2 32 Vo 2h 16 | 16.8 427 2542 %
5. BRONCHUS M_ 66 47 94 «7 39si8 CSCC sd KTS
6. proncsus M 52 | 35 4 70 21 126 . 8 46 272 39° 75 | 69.6 460 66) ¥
7. provcxus F 48 [| 12 33. 30 5 16. 2 45 24 -81 57 | 29.3. 90° “307%
8. BRONCHUS F 64 7 1 2% 13.72 14 4 30 103 2 "J 272 187 690%
9, BRoncHuS M 70 | 24 8 20 7 62 20- 5S 42 19 49 [25.5 S58 227%:
0, BRONCHUS M 78 32 19 39 40 24 2 43 103 2 21 | 34.4 ‘52. 15h
2. BRONCHUS: M-72 | 5 53 7 30 2 § 20 39 3L 16. | 20.8. 100° 48} 8.
2. BRONCHUS M 70 3 2 33 24 2 35 25 62. -2 63 27.4 | 1F0+ 6208
3, sroncnus M 39° | 420 31 74 «5S 88. .45..28...3-.15.- 70. | 40.1 "42° 1098
4c—BRONCHUS-M—-70---f 2g4-— 2 30S 42 G4 7ST «| 25.5 167, 65$ 4%
1S. BRONCHUS M 70 8 34 29 24 #+%S. 4 32 129° 20 51 [40.7 33° 81%
6, OESOPHAGUS M 72 : 12 2k 19 14 = 81 26 “59 21 28 33 57.4 50 . 87%.
17, OESOPHAGUS F 80 f 2 29 6 (4s 482413" 238 “56 2 | 46.3 43° 93%
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$1. COLON mM 69 | 48 9 7 15 30 90 26 94° 38 15 37.3, 1267 143438
2. couon = «OF «70:~«L Ga 0213 wes 14k UT sda + 2740
33. COLON F 68 ( 9 JS 40 LL 17 2u7 163 53 «18 38 38.5 170 14438
34. COLON * OM (SO 7108 #7 #18 #17 #14 SL 69 16 (32) 133.8 428 12668
35. COLON F 74 '11. 45 5SO "6 18 2 40 11 88 23 31.8 j#7+ 399%
36. COLON A 66 13 #7 224 3h 72 WoL 4 YW 14° 438.8 58 1498
37. COLON F 76 +23 129° 8 63 60 21 28 3 15 70 | 43.8 493+ 212%
38. COLON FS6 $24. 1 30 2- S 42 46 41 7 57 | 25.5 86x 33768
39. RECTUM F 56 51 406 74 36° 41 106 30 82 82 98 hoo.6 62 62%
40, RECTUM FO7S" 3 40 46 #58 7 9-19 -68 16 178 | 44.4. 223 502%

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KIDNEY(Ca)  M
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(Footnote to Table 1)

4 The sign + following the survival time of the patients treated with
ascorbic acid means that the patient was alive on 10 July 1976.
Parantheses ( ) 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.

*Diffuse urinary tract papillomatosis. The test cases (78 and 79)
had lesions in both kidney and bladder. The nine control cases indicated
by the asterisk had tumor of identical histology, but with their disease

confined to bladder mucosa.
Table 2
Ratios of Average Survival Times for Ascorbate Patients and Matched

Controls, with Statistical Significance

A B Cc D E F G H I

Bronchus (15) 134d 38.5d 3.48 47d 47% 8.7% 24.5 <<0.0001

Colon (13) 275 37.0 7.42 59 54% 20% 7.63 <0.003
Stomach (13) 94.3 37.9 2.49 43 46% 17% 6.41 <0.006
Breast (11) 362 64.0 5.66 91 55% 22% 5.74 <0.026
Kidney (9) 330 64.0 5.16 88 67% 22% 8.35 <0.002
Bladder (7) 192 43.6 4.39 a7 57% 20% 4.90 <0.028
Rectum (7) 222 95.5 4.00 71 86% 33% 7.57 <0.003
Others (25) 158 60.2 2.62 72 44% 28% 2.64 <0.052
All (100) 204.2 50.3 4.06 64 61% 25% 57.66 <<0. 0001

A. Type of cancer and number of ascorbate patients. Ten matched controls
for each ascorbic acid patient.

B. Average days of survival for ascorbate patients.

C. Average days of survival for controls.

D. The ratio B/C.

E. Average days of survival for all subjects in group.

F. Fraction of ascorbate patients surviving longer than E.
G. Fraction of controls surviving longer than E.

H. Value of y? for F and G (two-by-two calculation).

I. Corresponding value of P (one-tailed).
DEATHS,

percent

90

25

20

15

10

 

 

 

NWS
ang

 

 

 

 

LL

 

 

 

 

 

 

22%

9.5%:

 

10%

 

 

1.9%

 

 

 

 

 

 

 

NSS

 

 

 

 

CONTROLS

=] PATIENTS RECEIVING

ASCORBATE

7% 7%

 

4%

 

 

 

 

0% ae

 

T
© f-.

100-199 200— 299 300 499 500— 899 900—

SURVIVAL TIME, days

Figure 1

L. Pauling
Legend for figure

Figure 1, The percentages of the 1000 controls (matched cancer patients)
and the 100 patients treated with ascorbic acid who survived by the indicated

number of days after being deemed untreatable.