Significant Survival Benefit to Patients with Advanced Non-Small-Cell Lung Cancer from Treatment with Clarithromycin

Abstract

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 patiens (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 patiens and that it can increase the median survival of patients with advanced disease.

Clarithromycin attenuates autophagy in myeloma cells

“…Despite our findings only referring to myeloma cells, a similar phenomenon may be found in various tumor cells, which show a survival benefit following treatment with CAM, such as lung cancer cells (1)(2)(3)(4)(5)27,28). In this context, unveiling of mechanisms regulating autophagy by CAM should be important not only for understanding the biology of cancer cells but also extending survival of cancer patients.…”

“…Prolonged survival of lung cancer patients treated with macrolides, and experiments showing anti-tumor activity of CAM have been reported (1)(2)(3)(4)(5). In experimental settings, various effects of macrolides have been reported, e.g., anti-angiogenesis (6) and direct antitumor activity (7).…”

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study

“…In proposing its long-term use as a cachexia treatment, we consider additional caution appropriate, particularly given concerns about prolongation of the QT interval and the increased risk of ventricular arrhythmias and sudden cardiac death observed in patients receiving CLM (and other macrolides) [16]. Previous studies of CLM for cancer cachexia predate the emergence of these safety concerns [7,8].…”

“…Given the preliminary reports of impressive benefits of CLM in cancer cachexia [7,8], rather than abandon this area completely, the potential exists to explore the feasibility of using alternate macrolide antimicrobials. For example, although azithromycin has no 'track record' in cachexia, it also has immunomodulatory properties [17,18], is used long-term [19,20], and has a lower risk of a drug-drug interaction, such that only 10 of our patients would have been excluded on this basis.…”

“…No standard treatment exists and cachexia is a major unmet need [5,6]. Clarithromycin (CLM) is reported to preserve body weight, physical independence and increase survival in patients with lung cancer [7,8]. The mechanism may relate to its anti-inflammatory effect as inflammation appears a key contributor to cachexia [9][10][11].…”