Clinical Briefs

By Louis Kuritzky, MD

Antioxidant Supplements for Prevention of Gastrointestinal Cancers: A Systematic Review and Meta-Analysis

Clinicians and patients have hoped that antioxidants might prevent cancer. Since oxidant stress may be one of the culprits in gene mutation that leads to carcinogenesis, it was logical to entertain the therapeutic potential of antioxidant supplements. Observational studies have been generally supportive of potential benefits from antioxidants, but of course randomized interventional trials trump observational data as an evidence source.

This meta-analysis reviewed trials of antioxidants for prevention of GI cancer. Inclusion criteria required that the trials be randomized and placebo controlled. Trial quality was ranked overall as high (n = 14 trials, study subjects = 170,525). Antioxidants addressed included beta-carotene, selenium, and vitamins A, C, and E.

In the overall analysis, none of the nutrients favorably impacted cancer incidence, although in 4 trials (3 of which are quoted as having unclear or inadequate methodology), selenium favorably affected GI cancer. Disturbingly, there were several trials that showed either increases of cancer, mortality or both. Despite our common-sense attraction to use antioxidants, convincing beneficial effects remain to be demonstrated.

Bjelakovic et al. Lancet. 2004;364: 1219-1228.

Imiquimod 5% Cream for the Treatment of Actinic Keratosis

Recent changes in dermatologic nomenclature classify actinic keratosis (AK) as keratinocytic intraepidermal neoplasia, or carcinoma in situ. A variety of treatments provide destruction and resolution of AK. Most of the time, biopsy is not performed, but rather, topicals like 5-fluorouracil are applied until a typical inflammatory cutaneous response exfoliates the lesions. Because the adverse effects of traditional treatments may be problematic, and the efficacy of standard therapies is imperfect, additional modalities are welcome.

Imiquimod 5% (AldaraTM) is a commonly used topical immunomodulator for treatment of genital warts. It is also no approved for the treatment of AK. This investigation studied the efficacy of imiquimod (compared to placebo vehicle cream) applied 3 times weekly for 16 weeks to biopsy-proven AK in 286 patients.

Complete clearance of AK was seen in 57.1% of imiquimod patients, vs 2.2% of the placebo group. The most common adverse events associated with treatment were local cutaneous reactions of burning, erythema, itching, pain, and soreness. One or more of these adverse events were seen in the majority of patients, and essentially all patients experienced erythema. No serious adverse effects were attributed to imiquimod. Imiquimod may be considered a reasonable topical treatment for patients in primary care settings presenting with AK.

Saeimies RM, et al. J am Acad Dermatol. 2004;51:547-555.

Two 8-month Regimens of Chemotherapy for Treatment of Newly Diagnosed Pulmonary Tuberculosis

The epidemiologic presence of tuberculosis has grown greater to some degree because of the sustained and evolving population of HIV-infected individuals worldwide. Standard therapy (as per the World Health Organization) for newly diagnosed smear positive tuberculosis has been a 6-month course of isoniazid (I) and rifampicin (R). Short course regimens are usually structured to include a 2 month intensive phase during which 4 drugs are given [ethambutol (E), isoniazid (I), rifampicin (R), and pyrazinamide (P)], followed by a 4-6 month 2 drug phase (I + R) .

This trial compared an 8-month regimen based upon ethambutol (E) and isoniazid with standard 6 month therapy. Two different 8-month regimens were used: Daily E+I+R+P for 2 months followed by E + I, or thrice weekly E+I+R+P for 2 months followed by E + I. The outcome of culture negativity was monitored at 2 months and 12 months.

Neither of the 8-month regimens provided superior outcomes to the traditional 6 month regimen. Thrice weekly multi-drug administration was less efficacious than daily. The standard 6-month regimen should remain preferred.

Jindani A, et al. Lancet. 2004;364: 1244-1251.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.