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LE Magazine March 2001

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Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes.

BACKGROUND: Previous studies have suggested that cimetidine, a histamine-2 receptor antagonist with immunostimulatory effects, may improve survival in patients with colorectal carcinoma. This effect may be apparent by an increase in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative treatment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritumoral lymphocytes. METHODS: One hundred and twenty-five patients who were scheduled to undergo elective colon or rectal excision for carcinoma were randomized to receive either placebo or cimetidine preoperatively for 5 days. In addition to standard histopathology, immunohistochemistry and computer video image analysis were used to assess the number of peritumoral lymphocytes in an objective manner. Interim survival analysis according to the Kaplan-Meier method was performed. RESULTS: A trend toward a survival advantage in the group of patients receiving cimetidine (800 mg twice daily) compared with the placebo group was observed (P = 0.20, log rank test) that was most marked in patients with replication error negative tumors (P = 0.04). Similarly, in these two groups there was a trend toward an increase in the number of patients with a conspicuous lymphocytic infiltration (P = 0.10, chi-square test). However, there was no difference in the number of peritumoral lymphocytes as measured by image analysis. CONCLUSIONS: Based on the results of the current study, a short course of preoperative treatment with cimetidine does appear to have an effect on patient survival; however, the exact mechanism is unknown. The failure of this study to demonstrate a clear increase in the local lymphocyte response does not exclude an immunologic mechanism of action.

Cancer 1999 Apr 15;85(8):1658-63

Efficacy of cimetidine in treatment of Herpes zoster in the first 5 days from the moment of disease manifestation.

221 patients with Herpes zoster have undergone the treatment. They were given cimetidine in the daily dose 3 x 200 mg and 1 x 400 mg to night. It was proved that the efficacy of the Herpes zoster treatment by cimetidine is inversely proportional to the time of the disease duration. The authors suggest to use cimetidine in the treatment of Herpes zoster virus infections even during the prodromal period.

Pol Tyg Lek 1996 Jun;51(23-26):338-9

Oral cimetidine for the management of genital and perigenital warts in children.

PURPOSE: It is believed that most warts are self-limiting and generally require little or no treatment. When numerous or almost complete infestation of the perineum, genital area and groin is encountered it can be distressing and a difficult problem to treat in children. Multiple treatments with caustic agents are sometimes necessary, and treatment of perigenital warts may require use of anesthesia for multiple procedures. Cimetidine is a histamine receptor antagonist that has been used mainly to treat peptic ulcer disease. Recently it has been reported to be useful for the treatment of mucocutaneous candidiasis, herpes simplex, herpes zoster and verruca because of its immunomodulatory effects. Several studies have been published indicating its effectiveness in the treatment of warts. MATERIALS AND METHODS: We treated 4 children with extensive condylomata acuminata of the genital and perigenital areas with high doses of cimetidine in an attempt to eradicate the condyloma and avoid recurrence in 2 and as primary treatment in 2. All patients were treated with 30 to 40 mg./kg. cimetidine daily in 3 divided doses during a 3-month period. RESULTS: All patients are free of condyloma at 24 months following treatment. CONCLUSIONS: Our results show that cimetidine is useful for primary and adjunctive treatment of condyloma in young children. It also appears to be effective as first line therapy.

J Urol 2000 Sep;164(3 Pt 2):1074-5

In vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine.

In a double-blind placebo-control study the immunomodulating effect of cimetidine treatment for one week and placebo was investigated for cell-mediated immune reactions of 22 patients with herpes zoster (HZ). The mitogen induced leukocyte migration inhibition test (LMIT) and the in vitro proliferation of the patients' lymphocytes to exogenous IL-2 were used. Before any treatment, the mitogen induced leukocyte migration inhibition capacity (LMIC) of HZ patients was found to be significantly reduced (p < 0.02) as compared to healthy blood bank donors (controls). After one week, within the same treatment, the LMIC was significantly improved (p < 0.01). The patients' lymphoproliferative response to IL-2, before any treatment, was not significantly different from that of controls (p < 0.05). However, significantly higher values (p < 0.001) were found in patients tested 7 days after the disease onset as compared to those tested after 12 days. One-week cimetidine treatment significantly improved (p < 0.05) the lymphoproliferative response to IL-2 of initially low responders and had no effect on higher responder patients. In contrast to this, after one week of placebo treatment, a significant decrease in the patients' lymphoproliferative response to IL-2 could be observed as compared to patients' initial responses (p < 0.05) or to those of controls (p < 0.05). Although the number of cases is very small. The data suggest that after cimetidine treatment, as compared to placebo, healing from skin rash and pain was achieved in a significantly shorter time (p < 0.01).

Asian Pac J Allergy Immunol 1994 Jun;12(1):51-8

Cimetidine as an immunomodulator in the treatment of herpes zoster.

As there is evidence of a possible immunoregulatory role for H2-histamine receptor antagonists, we carried out a prospective randomized trial to evaluate the in vivo and in vitro effect of cimetidine, an H2-blocker, in the treatment of herpes zoster infection. Cimetidine treatment shortened the median interval until the first decrease in pain, the median interval until the complete resolution of pain and promoted faster complete healing of skin lesions than symptomatic treatment. The immunological trends observed in vitro support an important role for histamine in the induction of immunosuppression, as measured by the response to the mitogen phytohemagglutinin. This effect of histamine was antagonized by cimetidine.

J Neuroimmunol 1989 Mar;22(1):69-76

Cimetidine: an immunomodulator.

Suppressor T lymphocytes possess histamine2 (H2) receptors and contribute significantly to the function of the immune system. Experimentally, cimetidine, an H2-receptor antagonist, has been shown to enhance a variety of immunologic functions both in vivo and in vitro because of its inhibitory effects on suppressor-cell function. Successful tumor immunotherapy, as well as some protection from infection, has been reported in experimental animals. Patients receiving cimetidine have been shown to exhibit enhanced cell-mediated immunity as evaluated by increased response to skin-test antigens, restoration of sensitivity following development of acquired tolerance, and increased responses of lymphocytes to mitogen stimulation. Preliminary reports also indicate that cimetidine may offer therapeutic benefits for patients with Varicella zoster and Herpes simplex infections, as well as those suffering from mucocutaneous candidiasis and common variable hypogammaglobulinemia. These immunoregulatory effects are dose-related but are not always consistent. Because of its inhibitory effect on suppressor function, cimetidine treatment may be deleterious in patients with organ transplant and autoimmune disorders. Cimetidine should be used as an immunomodulator on an experimental basis only.

DICP 1990 Mar;24(3):289-95

Cimetidine therapy for warts: a placebo-controlled, double-blind study.

BACKGROUND: Cimetidine, an H2-receptor antagonist, has been used successfully to treat patients with mucocutaneous candidiasis, common variable immunodeficiency, herpes simplex, and herpes zoster because of its immunomodulatory effects. Recently, some trials have suggested that cimetidine may also be useful for the treatment of warts. OBJECTIVE: The aim of the present study was to determine whether cimetidine is effective in the treatment of warts. METHODS: Seventy patients with multiple warts were included in a placebo-controlled, double-blind study. Patients were randomly allocated to treatment groups equally. The groups received cimetidine, 25 to 40 mg/kg daily, or placebo for 3 months. Patients were examined at monthly intervals. RESULTS: At the end of the therapy, 28 cimetidine-treated and 26 placebo-treated patients were examined to determine the efficacy of treatment. Cure rates obtained were 32% (9 of 28) in the cimetidine-treated group and 30.7% (8 of 26) in the placebo-treated group. No significant difference was found between cimetidine and placebo in effectiveness (p = 0.85). CONCLUSION: Our results show that cimetidine is no more effective than placebo in the treatment of patients with common warts.

J Am Acad Dermatol 1996 Jun;34(6):1005-7

Cimetidine in the treatment of herpesvirus infections.

In August 1977 a patient developed herpes zoster just before she commenced a course of cimetidine (Tagamet; Smith, Kline & French) for a chronic gastric ulcer. She experienced both rapid relief of the ulcer symptoms and, rather unexpectedly, dramatic relief of the herpetic pain and rapid disappearance of the eruption. On the basis of this observation cimetidine was prescribed to 21 patients with herpes zoster. The results continued to be encouraging in all but 3 patients. The trial was therefore extended to other herpesvirus infections. In all but 1 of 7 patients with herpes labialis the blisters were aborted, and in 1 patient with herpes keratitis the result was also encouraging, the attacks being markedly shortened in duration and reduced in frequency. The results of this preliminary trial warrant a systematic scientific inquiry into the potential role of cimetidine in the treatment of hypesvirus infection, as well as a study of the mechanisms involved.

S Afr Med J 1980 Jul 19;58(3):112-6

Viral infections in severely immunocompromised cancer patients.

Immunocompromised cancer patients are susceptible to infection by many viral pathogens. The most serious morbidity results from active infection by members of the herpes virus family. Reactivation of latent virus occurs as a sequela of cytotoxic therapy and deficiency of cell-mediated immunity, especially cytotoxic responses, the major host protective defense. Herpes simplex virus and varicella zoster virus infections are problematic in patients with all types of cancer; cytomegalovirus infections cause life-threatening morbidity in bone marrow transplant patients. Several antiviral agents are highly active against these pathogens and different strategies of using them have resulted in reduced morbidity and mortality. Ultimately, the resolution of these infections is dependent on the control of the malignancy and the ability of the patient to mount an adequate immune response.

Support Care Cancer 1994 Nov;2(6):355-68

Herpes zoster: treatment with cimetidine.

The active phase of herpes zoster can be predicted from the length of time it takes for all the vesicles to erupt. A case is reported in which cimetidine therapy appeared to reduce the expected length of the active phase from 35 days or longer to 10 days.

Can Med Assoc J 1983 Dec 15;129(12):1284-5

Immunomodulatory properties of cimetidine in ARC patients.

The immunomodulatory potency of cimetidine, a histamine H2 receptor antagonist, was investigated in 33 AIDS-related complex (ARC) patients performing detailed immunological and clinical evaluations. Cimetidine was administered orally in daily doses of 1200 mg for a period of 5 months with an interruption of therapy after the first 3 months for an interval of 3 weeks. Significant (P less than 0.05) elevations of immunoglobulins (IgG, IgA), complement C4, B-lymphocytes, and OKT4+ (helper/inducer) cells were found after cimetidine intake. The in vitro lymphocyte proliferative response to plant mitogens was significantly increased, and the in vivo cell-mediated hypersensitivity reaction assessed by intradermal application of seven recall antigens improved significantly. These effects were both reversible with the discontinuation of cimetidine and reproducible with repeated administration of the drug. Clinical data such as performance status, body weight, and fever were influenced favorably (P less than 0.05) by cimetidine. The frequency of diarrhea and the lymph node size were also diminished significantly. The data suggest that cimetidine may at least partially restore immunofunctions in AIDS-related complex.

Clin Immunol Immunopathol 1988 Jul;48(1):50-60

Effect of cimetidine on herpes zoster infection.

Cimetidine was administered to two patients for herpes zoster infection. An acute pain-relieving effect was observed. The patients were followed for 11 and 14 months without developing postherpetic neuralgia. Possible mechanisms for prevention of postherpetic neuralgia by cimetidine are discussed.

Drug Intell Clin Pharm 1987 Oct;21(10):803-5

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