CIMETIDINE (TAGAMET) AS IMMUNOMODULATOR, ANTITUMOR TREATMENT?

Cimetidine (Tagamet), commonly used to treat stomach ulcers and one of the most widely prescribed drugs in the U.S., has shown immune enhancing and antitumor activity in recent studies. In its original use, cimetidine worked by blocking the receptors on stomach cells which control digestive acid secretions. Cimetidine has also been shown to be useful for controlling herpes simplex and herpes zoster outbreaks, as well as chronic Epstein-Barr infection. (Cimetidine can slow the metabolism of other drugs, leading to increased concentrations of them in the bloodstream. This is important for drug interactions/half-life considerations.)

The results of the current studies demonstrated variously that cimetidine appeared to increase in vitro the proliferation and potency of lymphocytes, probably by stimulating interleukin-2 production; increased the median survival time of patients with gastric cancer and possibly lung cancer as well; enhanced natural killer activity in patients with leukemia; and reduced T8- suppressor cell activity in patients with hypogammaglobulinemia. The most interesting research relating to HIV was done at the University of Essen in West Germany. 1200 mg of cimetidine was given daily to 33 patients with ARC for five months. All of the participants showed improvement of symptoms, such as decreased fevers, diarrhea and lymph node size, and increased body weight and sensitivity to skin antigen tests. Significant increases in several immune functions were noticed, including elevated T-helper cell counts. These effects were reversible when cimetidine was stopped, and reproducible when resumed.

We spoke with S. Jeanne Bramhall, M.D. who conducted her own informal cimetidine monitoring project with five patients in Seattle. All five patients experienced relief from a number of AIDS or ARC symptoms, apparently after several weeks of Tagamet, 300 mg three times daily. Here is a brief summary of the results:

Patient 1: After three weeks on Tagamet and imipramine, her fatigue, night sweats and lymphadenopathy disappeared completely. These symptoms returned when the patient stopped the Tagamet, and disappeared again when she resumed. Her T-cell ratio returned to normal and the symptoms did not recur when she discontinued the Tagamet after a second three-month trial. This patient has since been lost to follow-up.

Patient 2: Experienced relief of disseminated herpes lesions and thrush after two weeks of Tagamet, and after three months a diagnosed Kaposi's sarcoma lesion in his mouth vanished. His T- cell ratio was improving after eight months, and he had added amitriptyline, acyclovir and ketoconazole to his medications. He also wanted to start AZT, but was apprehensive about the poten- tial for cimetidine to increase the toxicity of certain drugs. To avoid this he replaced Tagamet with ranitidine (Zantac), a related drug which studies found somewhat as active as an immunomodulator but less likely to potentiate the toxicity of other drugs. After switching he suffered several bouts with a persistent staph infection and two episodes of PCP. He was also lost to follow-up.

Patient 3: Started Tagamet after hospitalization for pneumocystis. He noticed increased energy levels and diminished oral thrush and enrolled in a local AZT study. After three months the AZT had caused anemia severe enough to warrant a transfusion (bone marrow toxicity is not unusual with AZT but perhaps the potential for toxicity was enhanced with Tagamet). He elected to discontinue both medications and after a month the anemia was corrected. He now takes no medication other than Chinese herbs, but seven months after the Tagamet he has seen four KS lesions subside and has gained 25 pounds.

Patient 4: After a month on Tagamet, his persistent leukoplakia, intermittent fevers and diarrhea all subsided. After five months, he discontinued the Tagamet and megavitamins, thinking that they were causing a recurrence of diarrhea. At the time he was lost to follow-up, he was not on any medication and had remained symptom-free.

Patient 5: Fatigue decreased dramatically after one week on Tagamet, but oral thrush persisted until he increased the dose to 400 mg three times a day for a week. He discontinued Tagamet and continues to be in good health.

Dr. Bramhall is not a researcher and did not have access to substantial funds or resources. But her anecdotal results should be a springboard for more and larger studies. She points out that cimetidine is relatively a very safe drug and is available now to people with HIV and their physicians. Our thanks to Dr. Bramhall for her work and to Jonathan Lax and Jim Tavitian for helpful information. We hope to find more information on this potential treatment at the V International AIDS Conference in Montreal.

References

Brockmeyer, NH and others. Immunomodulatory properties of cimetidine in ARC patients. Clinical Immunology and Immunopathology, number 48, pages 50-60, 1988

Tonnesen, H and others. Effect of cimetidine on survival after gastric cancer. The Lancet, October 29, pages 990-991, 1988.

Gifford, RRM and Tilberg, AF. Histamine type-2 antagonist immune modulation II. Cimetidine and ranitidine increase interleukin-2 production. Surgery, volume 102, number 2, pages 242-247, August, 1987.

Allen, JI and others. Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia. Journal of Laboratory Clinical Medicine, volume 109, number 4, pages 396-401, April 1987.

White, WB and Ballow, M. Modulation of suppressor-cell activity by cimetidine in patients with common variable hypogammaglobulinemia. The New England Journal of Medicine, volume 312, number 4, pages 198-202, January 24, 1985.

Armitage, JO and Sidner, RD. Antitumour effect of cimetidine? The Lancet, pages 882-883, April 21, 1979.