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Improved Survival in Patients With End-Stage Cancer Treated With Coenzyme Q10
Improved Survival in Patients With End-Stage Cancer Treated With Coenzyme Q10
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Improved Survival in Patients with End-Stage Cancer Treated with Coenzyme Q10 and other Antioxidants: A Pilot Study
N Hertz and RE Lister Journal of International Medical Research 2009 37: 1961 DOI: 10.1177/147323000903700634 The online version of this article can be found at: http://imr.sagepub.com/content/37/6/1961
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The Journal of International Medical Research 2009; 37: 1961 1971 [first published online as 37(6) 11]
Improved Survival in Patients with Endstage Cancer Treated with Coenzyme Q10 and Other Antioxidants: a Pilot Study
N HERTZ1
1
AND
RE LISTER2
Arnakkegrds alle 50, Vipperoed, Denmark; 2Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, London, UK predicted survival time was calculated from KaplanMeier curves for each patient at inclusion. Median predicted survival was 12 months (range 3 29 months), whereas median actual survival was 17 months (1 120 months), which is > 40% longer than the median predicted survival. Mean actual survival was 28.8 months versus 11.9 months for mean predicted survival. Ten patients (24%) survived for less time than predicted, whereas 31 (76%) survived for longer. Treatments were very well tolerated with few adverse effects.
This pilot study evaluated the survival of patients with end-stage cancer who received supplements of coenzyme Q10 and a mixture of other antioxidants (e.g. vitamin C, selenium, folic acid and bcarotene). During a period of 9 years, 41 patients who had end-stage cancer were included. Forty patients were followed until death and one patient was lost to follow-up and presumed dead. Primary cancers were located in the breast, brain, lungs, kidneys, pancreas, oesophagus, stomach, colon, prostate, ovaries and skin. The median KEY WORDS: END-STAGE
CANCER;
ANTIOXIDANTS; COENZYME Q10; SURVIVAL antioxidants seems to be more effective than individual antioxidants alone.18 20 Reactive oxygen species are able to activate all stages of carcinogenesis.21 Simplified, this process can be regarded as a continuous growth and accumulation of mutations in a cellular clone. If combinations of antioxidants have a preventive effect, it would seem possible that they would also retard the process at a later stage, i.e. when the cancer is apparent. A controlled study of patients with cancer of the urinary bladder seems to support this notion.22 The present report describes a pilot study in which consecutive patients with end-stage cancer
Introduction
In spite of unfavourable experiences with carotene, in particular an increased incidence of lung cancer (but not other kinds of cancer) among smokers in some large trials,1 3 it is still possible that antioxidants can assist in preventing cancer. This is supported by extensive evidence from molecular biological data,4 7 tissue and animal experiments,8,9 as well as epidemiological surveys.10 12 A few intervention trials have even indicated a protective effect of certain antioxidants, including -carotene and selenium.13 17 It is especially noteworthy that a combination of
1961
TABLE 1: Antioxidant treatments given to the 41 patients with end-stage cancer as a supplement to their usual cancer therapy Daily dosage (divided in two daily doses)
Antioxidantsa
Vitamin C 5.7 mg -Tocopherol 1.625 mg Coenzyme Q10 300 mg Selenium (as selenomethionine) 487 mg Folic acid 5 mg Vitamin A 25 000 IU -Caroteneb 76 mg
addition, patients received small amounts of linoleic acid (375 mg) and fish oil (1.5 mg), as well as niacin 45 mg, pantothenic acid 22.5 mg, vitamin B12 13.5 g, vitamin B6 12.6 mg, vitamin B2 8.4 mg and vitamin B1 5.4 mg. bFor safety reasons, patients with lung cancer did not receive -carotene.1 3
aIn
TREATMENTS
Patients were offered treatment with Q10 and other antioxidants as a supplement to their
1962
TABLE 2: Previously published prognostic data used to determine the median predicted survival time (MST) of patients with intrathoracic metastases from breast cancer Source Gawne-Cain et al. Banerjee et al.26 Clark et al.27 Blanco et al.28
25
TABLE 3: Previously published prognostic data used to determine the median predicted survival time (MST) of patients with bone metastases from breast cancer Source Clark et al. Blanco et al.28 Koenders et al.29 Total Chosen median
27
MST (months) 19 19 34 21
TABLE 4: Previously published prognostic data used to determine the median predicted survival time (MST) of patients with cerebral metastases Source Clark et al.27 Sampson et al.30 Schoeggl et al.31 Sundstrm et al.32 Lagerwaard et al.33 Primary cancer Breast Malignant melanoma All types All types All types Total Chosen median
aA bMedian
total of 84% of the patients were treated with whole brain radiation. survival was 8.9 months for patients treated with whole brain irradiation and surgery.
1963
STATISTICAL ANALYSIS
According to the null hypothesis, the number of patients surviving longer than expected would equal the number surviving shorter than expected. The median gain or loss in survival and the number of patients surviving shorter or longer than predicted were calculated, and differences in the median predicted and median actual survivals were compared by the Wilcoxon signed rank test using Minitab statistical software, version 15 (Minitab Inc., Pennsylvania, USA). A P-value < 0.05 was considered to be statistically significant.
Results
PATIENTS
A total of 103 patients with end-stage cancer
1964
TABLE 5: Expected and actual survival for the 41 patients with end-stage cancer who were treated with coenzyme Q10 and other antioxidants Expected survival Achieved at inclusion survival (months) (months) 11 19 3 5 10 13 16 8 25 113 3 3 22 19 18 10 1 10 5 15 25 21 21 17 33 34 37 43 66 82 120 111 89 6 2 13 25 8 13 79 4 28.7 17 Survival in excess of expected (month) 1 7 2 1 5 10 3 1 15 101 4 3 13 15 4 2 13 2 1 1 5 7 7 7 12 20 23 29 45 61 99 97 79 1 2 10 20 20 14 50 2 16.8 7**
Patient No. 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
Sex Male Male Male Male Male Male Male Female Male Female Male Male Male Male Male Female Female Female Female Female Female Female Female Female Female Female Female Female Female Female Female Female Female Female Male Male Female Male Male Male Male
Primary cancer Colon Colon Oesophagus Oesophagus Oesophagus Oesophagus Glioblastoma Grade 4 Kidney Kidney Kidney
Metastases
Liver 10 Liver 12 Lymph nodes 5 Mediastinum 4 Lymph nodes 5 Stomach 3 Incomplete 13 resection Both lungs 7 Liver 10 None, declined 12 operation Lung, non-small-cell Inoperable 7 Lung, non-small-cell Brain 6 Lung, non-small-cell Inoperable 9 Lung, non-small-cell Inoperable 4 Lung, small-cell Supraclavicular 14 lymph nodes Malignant melanoma Brain 8 Breast Lung 14 Breast Pleura 12 Breast Brain 6 Breast Liver 14 Breast Bones 20 Breast Pleura and bones 14 Breast Lungs 14 Breast Both lungs 10 Breast Bones 21 Breast Peritoneum, ovaries 14 Breast Both lungs, bones 14 Breast Lung and bones 14 Breast Bones 21 Breast Bones 21 Breast Scull, neurological signs 21 Breast Pleura 14 Ovary Liver 10 Pancreas Regional 5 Pancreas Regional 4 Pancreas Regional 3 Pancreas Liver 5 Prostate Bones 28 Prostate Bones 27 Prostate Bones 29 Stomach Regional 6 Mean 11.9 Median 12
**P < 0.002, 95% CI 4.0, 18.5 months (two-tailed Wilcoxon signed rank test).
1965
1966
120
120
100
100
80
60
60
40
40
20
20
0 1 20 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 Patient No.
40
FIGURE 1: Actual survival time relative to the predicted survival time, and the time to antioxidant treatment for the 41 patients with end-stage cancer treatment with antioxidants within 1.5 months of being diagnosed with metastases or otherwise being declared incurable. Among these, the actual median survival in excess of the predicted survival time was 7 months. The others (n = 21) began treatment > 1.5 months (median 5 months) after diagnosis. Among these the actual median survival in excess of the predicted survival time was 1.5 months (Fig. 1). Compliance with treatment was very good, although most patients had trouble taking all or any of the pills towards the end of their life. impressive improvement of their general well-being after beginning the antioxidant supplementation, although this was not measured.
CASE HISTORIES
Case 1 (patient 26) This 57-year old woman had a second breast cancer, the other breast having been removed 6 years earlier. At recurrence, she had considerable amounts of ascites, carcinosis of the peritoneum, cancerous transformation of the ovaries and omentum as well as growth of cancer around the rectum, which caused pain on defecation. Her case was considered terminal and she was offered no conventional treatment. After starting on antioxidants, her waist circumference after 3 months shrunk by 9 cm, which was presumed to indicate the disappearance of the ascites. She was feeling well and pursued an active life for the next few years, e.g. taking prolonged vacations abroad. The unexpected course of the disease
SIDE EFFECTS
Side effects associated with antioxidant therapy were very rare and minor, mainly consisting of difficulties in swallowing the many tablets and aversion to the odour of the tablets, particularly once their general physical condition had deteriorated. No other physical side effects were noted. The clear impression of the investigator was that a large majority of the patients experienced
1967
Discussion
Perhaps the most interesting finding of the present study was that the median (though not the mean) survival time in excess of that predicted was longer (7 versus 1.5 months) in the 20 patients who began antioxidant treatment within 1.5 months of being diagnosed than in those who began antioxidant treatment later. No evidence exists, however, that alternative therapy alone can improve survival in cancer. For example, shark cartilage was shown to have no effect on disease progression and no positive effect on quality of life in a trial that included 60 patients with advanced cancer.48 The strengths of the present study are that all cancer patients were accounted for and that the course of the disease was well illustrated in all patients. Its limitations include the retrospective design, lack of a matched control group and lack of blinding.
1968
Acknowledgement
Pharma Nord, Vejle, Denmark, supplied all medications free of charge without any kind of involvement with this project.
Conflicts of interest
The authors had no conflicts of interest to declare in relation to this article.
Received for publication 1 June 2009 Accepted subject to revision 4 June 2009 Revised accepted 13 October 2009 Copyright 2009 Field House Publishing LLP
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Authors address for correspondence Dr Niels Hertz Arnakkegrds alle 50, DK 490 Vipperoed, Denmark. E-mail: nhj@dadlnet.dk
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Corrigendum
N Hertz, RE Lister: Improved survival in patients with end-stage cancer treated with coenzyme Q10 and other antioxidants: a pilot study. J Int Med Res 2009; 37: 1961 1971. In Table 1 on page 1962, the units for selenium should be micrograms (g) not milligrams (mg). Also, the amount of vitamin C should be 5700 mg, not 5.7 mg. The amount of tocopherol should be 1625 mg, not 1.625 mg. In the footnote, the amount of fish oil should be 1500 mg not 1.5 mg. The correct version of Table 1 is, therefore, as follows:
TABLE 1: Antioxidant treatments given to the 41 patients with end-stage cancer as a supplement to their usual cancer therapy Daily dosage (divided in two daily doses)
Antioxidantsa
Vitamin C 5700 mg -Tocopherol 1625 mg Coenzyme Q10 300 mg Selenium (as selenomethionine) 487 g Folic acid 5 mg Vitamin A 25 000 IU -Caroteneb 76 mg
aIn
addition, patients received small amounts of linoleic acid (375 mg) and fish oil (1500 mg), as well as niacin 45 mg, pantothenic acid 22.5 mg, vitamin B12 13.5 g, vitamin B6 12.6 mg, vitamin B2 8.4 mg and vitamin B1 5.4 mg. bFor safety reasons, patients with lung cancer did not receive -carotene.1 3
293