Is Cimetidine (Tagamet) a Better Cure for Cancer?

Cimetidine

In 1979 The Lancet carried a letter from Drs. James O. Armitage and Robert D. Sidner, of the University of Nebraska School of Medicine, that reported a possible anticancer effect of cimetidine ⁽¹⁾ .

Cimetidine is a drug called a histamine ₂ -receptor antagonist that is commonly prescribed in cases of heartburn to reduce acid secretion in the stomach. With the trade name Tagamet , it is one of the world's most prescribed drugs. And as Tagamet , it is a non-prescription drug in most countries.

Squamous-cell carcinoma and lung cancer

Armitage and Sidner had two patients with lung cancer. One was a fifty-two year old woman, the other a seventy-one year old man.

The man came to the two doctors in March 1977 with a lump on the right side of his neck. Other than that he had no complaints. The lump was found to be a form of cancer called squamous-cell carcinoma . He was immediately put on a course of chemotherapy but that made him feel so sick that he refused to take it after the first cycle.

Over the next three months the tumour grew bigger and became increasingly painful. These symptoms led him eventually to accept a second course of chemotherapy but, again, after just five days of treatment, nausea forced him to stop.

By November 1977 the neck tumour had started to ulcerate. Radiation was given for six weeks and this time there was some apparent success as the tumour almost disappeared.

By Christmas he was experiencing some tummy upsets and heartburn and, on 27 December, he was prescribed cimetidine at 300 mg four times a day.

A month later a chest X-ray showed masses in his lungs for the first time. On the same day the cimetidine was reduced to 300 mg twice daily. Over the next three months the cancers in his lungs increased in size. In March 1978 he was advised to have further anticancer therapy. He refused but the cimetidine treatment continued.

Three subsequent chest X-rays up to October 1978 showed the lung tumours getting progressively smaller until by April 1979 the man was completely free of symptoms.

The woman came to Armitage and Sidner on 20 July 1978 complaining of headaches and loss of weight. On examination she was found to have large-cell cancer of the lung with a 4.5 cm metastasis (secondary tumour) in her brain. She received radiation treatment for the brain tumour but nothing for the tumour in her lung as it was not causing her any distress.

On 14 September a chest X-ray showed that the lung tumour had increased in size but still she received no treatment for it. Two weeks later, she complained of heartburn and was put on cimetidine 300 mg twice daily.

Her brain tumour was surgically removed on 1 November and biopsy confirmed its lung origin. She was discharged. The woman continued taking cimetidine and a subsequent X-ray showed that the lung cancer was reducing in size.

Armitage and Sidner were at a loss to explain why cimetidine should have such an effect on malignant tumours. They could see no possible mechanism whereby cimetidine could have worked in this way and suggested that, perhaps, what had occurred had been a spontaneous regression unconnected to the cimetidine treatment. Such regressions, while rare are not unheard of. Over the next couple of years, however, laboratory tests on mice showed that cimetidine did have a direct antitumour effect. ^{(2) (3)}

Malignant melanoma

In August 1982 The Lancet carried another letter ⁽⁴⁾ which reported a most remarkable case of the skin cancer, malignant melanoma, treated with cimetidine. This was the case of a 34-year-old man with melanoma in his groin which had spread to the abdominal and chest walls and his left thigh. The cancers were inoperable and, without treatment, death was certain.

By December 1981 he had refused chemotherapy and there had been a marked deterioration in his condition. The situation looked bleak as it was thought that the chemotherapy had held out the only hope.

As he had severe abdominal pain and vomiting, the man was put on cimetidine 1,000 mg per day. Immediately his condition improved with a speed which approached the miraculous. In just two weeks all his tumours had almost completely gone and he was back at work full time.

This letter also reported three other cases of melanoma treated with cimetidine. Two of them, a 45-year-old man and a 72-year-old woman, had advanced disease with secondary tumours to the liver. They were both given cimetidine at 1,000 mg per day. Despite having a hopeless prognosis, within just one week there was a marked improvement in both of them and, when the letter was written in July 1982, both were well, although a secondary tumour could still be seen by X-ray in the a lung of one of them.

The third case was a 35-year-old woman with very far advanced melanoma on her back. It was classified 'Stage IV' which is as bad as it gets. She had surgery to remove the melanoma followed by cimetidine together with coumarin. Within fourteen days there was a rapid recurrence of the melanoma affecting her armpit, chest wall and lung and she died five weeks later. In this case the authors suggest that her death might have been due to the concurrent use of coumarin. (Coumarin is a drug which stimulates macrophages , large scavenger cells in the blood that remove bacteria and other foreign organisms from blood or tissues.)

Cimetidine as an adjuvant treatment

Similar cases continued to be reported from around the world. From Sweden came a report in October 1982 ⁽⁵⁾ of six melanoma patients, five of whom had secondary tumours that had spread throughout their bodies, treated with interferon. In all cases interferon was the primary anticancer treatment. Borgström and co-workers report that no improvements were noticed in their patients with interferon alone. After three to eight weeks the six patients were given cimetidine. Soon after the cimetidine was added complete remissions were seen in two patients, there was partial remission in a third and the disease was stabilised in a fourth.

This was the first report of cimetidine being used as an adjuvant anticancer treatment with a conventional cancer treatment: in this case, interferon.

And so numbers of reports increased in frequency. From Dublin, Eire, Drs. Thornes and Lynch, treating melanoma, found that cimetidine had no effect on its own and suggested that pre-treatment with coumarin or interferon may be required. ⁽⁶⁾ In France cancers of the oesophagus, stomach, liver, ovary, kidney and gallbladder were treated with cimetidine and there was a clinical improvement in five of seven patients. ⁽⁷⁾ Two patients with stomach cancer (intermediate and high-grade non-Hodgkin's lymphoma) were treated with cimetidine at the Mount Sinai Medical Center, New York in 1987. ⁽⁸⁾ In both cases the tumours regressed. This form of cancer is one where spontaneous regression is extremely uncommon. In a trial conducted in hospitals in Copenhagen, Denmark published in 1988, ⁽⁹⁾ the effect of cimetidine on survival was investigated in 181 patients with gastric cancer. Immediately after surgery, or the decision not to operate, the patients were randomised in double-blind fashion to one of two groups: one to take cimetidine 400 mg twice daily for two years or until death, the other a placebo. They were reviewed every three months. The average survival in the cimetidine group was 450 days. This may not seem long, but it was significantly longer than the 316 days' average in the placebo group. At the end of each year of five years of follow-up, the cimetidine group had roughly twice the survival rate of the placebo group. And while two percent of the cimetidine patients survived longer than five years, none of those in the placebo group did.

Cimetidine reduces the immunosuppressive effects of conventional treatment

By the mid-1990s other clinical trials were being done and reported. One which had particular significance for me was into the use of cimetidine before, during and after surgery for colon cancer. ⁽¹⁰⁾ This trial was conducted by Dr Warwick Adams and Professor David Morris at University of New South Wales Department of Surgery, The St. George Hospital, Kogarah, Australia. It demonstrated very convincingly the benefit of cimetidine taken for seven days before surgery to reduce the immunosuppressive effects of the surgery: at the three year follow-up, ninety-three percent of patients in the cimetidine group were alive compared with only fifty-nine percent in the control group.

Cimetidine was also found to enhance the curative effects of chemotherapeutic drugs in colorectal cancer. Dr Sumio Matsumoto, at Japan's Fujita Health University, conducted a multicentre clinical trial using cimetidine to reduce appetite loss in patients with cancers of the colon and rectum receiving the chemotherapeutic drug 5-FU after surgery. ⁽¹¹⁾ After nearly four years, survival in the cimetidine-treated colon cancer patients was 96.3 percent, compared to 68.8 percent of the controls. In patients with cancer of the rectum the results were even better: all of the cimetidine-treated patients were still alive compared to only just over half of the controls.

Not all the clinical trials have come up with such favourable results as this. In a Danish pilot study of cimetidine at 400 mg per day or placebo in colorectal cancer a total of 192 patients who had undergone surgery for cancers of the colon or rectum were studied for forty months. This study found no difference between the two groups. In this trial, however, unlike in the Japanese study above, the cimetidine was not begun until three weeks after surgery. It may be that the immune system needs to be enhanced before surgery suppresses it for the best result.

By now it was known that cimetidine preserved the body's immune system after surgery and that it actively inhibited the growth of some cancers. In 1997 Adams and Morris investigated the effect of cimetidine on the local immune response to colon cancer. ⁽¹²⁾ In this study numbers of lymphocytes the white cells in the blood with which the immune system fights cancers were counted in patients who were scheduled to have surgery. They then planned to do a similar count after surgery and see whether one week's use of cimetidine immediately before, during and after the time of the operation had a beneficial effect on numbers of lymphocytes. In the twenty-four patients who had had a placebo, just under a quarter (five) had a positive response. In the eighteen patients given cimetidine, however, more than half (ten) had a positive response. The authors say that "the presence of a local lymphocyte response correlates with an improved 3-year survival".

Some histamine ₂ -receptor antagonists are more equal that others

Cancer cells like histamine. To a cancer cell histamine is food. The anticancer effect of cimetidine seems to be in its antihistamine properties which rob cancer cells of the nutrition they need to survive.

But there are histamine ₂ -receptor antagonists other than cimetidine: ranitidine, nizatidine, famotidine. These had not been studied in the same way as cimetidine and in 1996 the University of New South Wales Department of Surgery team conducted an investigation to see if ranitidine, marketed as Zantac and the biggest selling drug of all time, also inhibited tumour growth in laboratory cancer cell lines and in laboratory mice. ⁽¹³⁾ They found that where cimetidine did inhibit cell growth, ranitidine had no effect.

This was confirmed and enlarged upon by a similar study from the Ajou Institute for Medical Science, Suwon, Korea where the possible anticancer effects of ranitidine and famotidine were studied. ⁽¹⁴⁾ In this study rantidine had a slight effect that didn't reach statistical significance, while famotidine had no effect at all.

Who cares?

A friend of mine developed prostate cancer. It was operated on and he was told that they had got it all. Over the subsequent two years, however, the cancer returned and spread throughout his body affecting several organs and his spine. He had chemotherapy and radiation, neither of which did any good. Eventually, his doctor told him that there was nothing more the medical profession could offer and advised him to consult a local herbalist. The herbalist prescribed ginger tea. There are herbs that have anticancer properties. As far as I am aware, ginger is not one of them.

My friend told me all this in 1998 shortly after seeing the herbalist. It was at a time when I was researching cimetidine for this book. I was impressed with the cases of dramatic remissions in seemingly hopeless cases and I reasoned that even if it did not help in his case, it wouldn't do any harm. I suggested that he take cimetidine. As his doctor would be coming to see him later in the day, I gave my friend some of the medical journals containing papers applicable to his case. He could then show them to his doctor as evidence to back up a request that the doctor prescribe 1,000 mg of cimetidine a day.

The doctor came and my friend asked for cimetidine. His doctor, however, told him that cimetidine was not used for cancer and dismissed the evidence without even looking at it! As a result my friend didn't take cimetidine. He died a few weeks later. He might have died anyway, but where was the harm in his taking it?

I do!

In November 1998 I went to Alabama to visit friends. Afterwards my wife and I toured the Southern States. The north-eastern corner of Georgia, in the Blue Ridge mountains, was beautiful: just like the pictures one sees of New England in the Fall with maples and aspens clothed in vivid reds, oranges and golds; the mountains divided by verdant valleys and deep ravines through which ran streams and rivers that poured over waterfalls. It was idyllic but not to last. Two or three days before we were due to leave I noticed blood in my stools. Was it the return of the colon cancer I had had some years before? I hoped that it would go away. A few days later I returned home, located a source of cimetidine and started to take it.

After a week the blood was still there. I went to see my doctor.

"Have a look, that's the gold standard" my doctor told me. He arranged an appointment at the local hospital for a sigmoidoscopy (a look inside with an endoscope) to see if anything was amiss. My appointment wasn't for another three weeks. After one of them the symptoms disappeared and at sigmoidoscopy the surgeon could find nothing.

Had I had a recurrence of my cancer that the cimetidine had cured or had I merely damaged the inside of my bowel with, perhaps, something I had eaten? We will never know.

Conclusion

Cimetidine has been shown to have a significant anticancer effect on many different cancers. It is a cheap, generic drug that is available from pharmacies without prescription in the USA and in limited quantities without prescription in Britain. While it inhibits the uptake of some anticoagulant drugs, its side effects are negligible at the recommended dose of 1,000 mg per day and can safely be taken both for its anti-cancer properties in people with the disease or as a prophylactic if cancer is suspected.

Cimetidine is probably the easiest drug to obtain and is suggested as the drug of first choice when cancer is suspected. The recommended dose is 1,000 mg per day.

References

1. Armitage J O, Sidner R D. Antitumour effect of cimetidine? Lancet 1979; i: 882-3.
2. Osband M E, et al. Successful tumour immunotherapy with cimetidine in mice. Lancet 1981; i: 636-38.
3. Gifford R R M, Fergusson R M, Voss B V. Cimetidine reduction of tumour formation in mice. Lancet 1981; i: 638-40.
4. Thornes R D, Lynch G, Sheehan M V. Cimetidine and coumarin therapy of melanoma. Lancet 1982; ii: 328.
5. Borgström S, et al. Human leukocyte interferon and cimetidine for metastatic melanoma. N Eng J Med 1982; 307: 1080-81.
6. Thornes R D, Lynch G. Combination of cimetidine with other drugs for treatment of cancer. N Eng J Med 1983; 308: 591.
7. Burtin C, et al. Combination of cimetidine with other drugs for treatment of cancer. N Eng J Med 1983; 308: 591-2.
8. Strauchen J A, Moran C, Goldsmith M, Greenberg M. Spontaneous regression of gastric lymphoma. Cancer . 1987; 60: 1872-5
9. Tonnesen H, et al. Effect of cimetidine on survival after gastric cancer. Lancet 1988; 2: 990-2.
10. Adams W, Morris D L. Short-course cimetidine and survival with colorectal cancer. Lancet 1994; 344: 1768-9.
11. Matsumoto S. Cimetidine and survival with colorectal cancer. Lancet 1995; 346: 115.
12. Adams W J, Morris D L. Pilot study cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: results of a small randomized control trial. Cancer 1997; 80: 15-21.
13. Lawson J A, Adams W, Morris D L. Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth. Br J Cancer. 1996; 73: 872-6.
14. Hahm K B, et al. Comparison of antiproliferative effects of 1-histamine-2 receptor antagonists, cimetidine, ranitidine, and famotidine, in gastric cancer cells. Int J Immunopharmacol . 1996; 18: 393-9