Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.

Animals↗

PubMedDate not supplied

Antitumor effect of erythromycin in mice.

Oral administration of erythromycin in the dose range of 1-10 mg/kg increased the survival times of tumor-bearing mice in both allogeneic and syngeneic mouse systems by two- to three-fold as compared with those of vehicle control mice, with the maximum effect at a dose of 5 mg/kg/day. During the early phase of tumor transplantation, tumoricidal macrophages and natural killer cells were active in the antitumor resistance of erythromycin-treated mice. Thereafter, the tumoricidal activity of macrophages became stronger as serum levels of interleukin-4 (IL-4) rose. Furthermore, treatment of mice with anti-IL-4 monoclonal antibody abolished the antitumor resistance conferred by erythromycin. These results indicate that erythromycin exhibits an indirect antineoplastic activity by enhancing the production of IL-4 which augments the tumoricidal activity of macrophages.

Administration, Oral↗

PubMedDate not supplied

Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin.

We carried out a randomized study of 49 consecutive patients with unresectable primary lung cancer to determine whether clarithromycin (CAM), a 14-membered ring macrolide, can improve outcome. A total of 49 patients (42 patients with non-small-cell lung cancer and 7 patients with small-cell lung cancer) had received prior chemotherapy, radiotherapy or both during their hospital stay. They were randomly allocated into two study groups on the first visit after discharge: 25 patients (22 patients with non-small-cell lung cancer, 3 patients with small-cell lung cancer) were assigned to receive CAM (400 mg/day, orally), and 24 patients (20 patients with non-small-cell lung cancer, 4 patients with small-cell lung cancer) did not receive CAM. CAM treatment after randomization was open and the treatment was to be continued as long as the patients could tolerate CAM. There was no significant difference in the median survival time for small-cell lung cancer between the CAM group and the non-CAM group. However, CAM treatment significantly increased the median survival time for non-small-cell lung cancer patients, the median survival for the CAM group was 535 days and that for the non-CAM group was 277 days. Analyses of prognostic factors showed that only treatment with CAM was predictive of longer survival for non-small-cell lung cancer, and other tested covariates had no effects on the prognosis. There were no remarkable side effects observed in the CAM group throughout treatment. We conclude that long-term treatment using CAM is beneficial for unresectable non-small-cell lung cancer patients and that it can increase the median survival of patients with advanced disease.

Aged↗

PubMedDate not supplied

Proliferation of erythromycin-stimulated mouse peritoneal macrophages in the absence of exogenous growth factors.

Erythromycin (0.2-20 micrograms/ml) induced the proliferation of macrophages of mouse peritoneal exudate cells (PEC) in a liquid medium without exogenous growth factors. The proliferating macrophages formed giant colonies between days 22 and 26 of culture; these colonies continued to proliferate even after subculture. The erythromycin-induced cell proliferation was independent of fibroblasts, T cells, B cells, or endotoxins. This activity seemed to be specific to erythromycin since other antibiotics such as tetracycline, streptomycin, gentamicin, penicillin G, and josamycin did not induce the proliferation of macrophages. Any known cytokines, including IL-2, IL-3, IL-4, IL-6, and GM-CSF, were not detectable by ELISA tests in any of the culture supernatants sampled from day 7 through day 28. The culture supernatants, however, had the capability of inducing the growth of macrophages, only in the presence of bioactive erythromycin at concentrations higher than 1.6 micrograms/l. Moreover, the culture supernatants, sampled after giant colonies had been formed, were capable of inducing giant colonies in the culture of adherent PEC. Thus, the erythromycin-induced macrophage proliferation might be due to the direct effect of this antibiotic, whereas the formation of giant colonies might be due to the production of some unidentified soluble factor produced by the proliferating macrophages. These data indicate that mouse PEC contain a subset of peritoneal macrophages capable of responding to erythromycin by forming proliferating colonies without exogenous growth factors.

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