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

Background

Cachexia, or weight loss is common in people with lung cancer, and it can be associated with poorer outcomes and shorter survival. It specifically involves the loss of muscle which results in reduced mobility and more need for help and care.

The primary objective was to obtain data to inform the feasibility and scale of a phase III study: based on rates of eligibility, reasons for exclusion, recruitment (over 1 year), data collection and study completion.

Secondary objectives were to obtain preliminary data on the:

• tolerability of CLM: based on adherence to treatment,
• safety of CLM: based on continual monitoring of toxicity, also electrocardiograms (ECGs) to detect prolongation of the QT interval (corrected for heart rate, QTc),
• effect of CLM on patient-centred outcomes: body composition, physical function, quality of life and systemic inflammation.

These data would ensure that a phase III study is viable, practical, uses appropriate primary and secondary outcome measures and is sufficiently powered.

‘’A large study might help us confirm whether CLM, an inexpensive antibiotic, has the potential to help patients who are suffering the effects of cachexia or weight loss associated with lung cancer.’’

What is the problem to be addressed?

Inflammation, which arises in response to the cancer, appears important in muscle loss. So, anti-inflammatory drugs may be helpful, but at present no standard treatment exists.

Preliminary work in people with non-small cell lung cancer (NSCLC) suggests that clarithromycin (CLM), an inexpensive antibiotic with anti-inflammatory effects, reduces inflammation, increases weight, and reduces the need for hospital admission and improves survival.

Therefore, CLM has the potential to be a helpful and cheap treatment. However, these were preliminary studies, and their findings must be confirmed in a large properly conducted study. We want to ensure that such a study is viable, practical, and well designed.

Findings and outcomes:

In his report to us, Dr Wilcock set out the intended aims of the project: 

‘’We invited people with incurable non-small cell lung cancer (NSCLC) to take part. Those agreeing were to be allocated, randomly, to receive for two months, either CLM or a placebo, produced as identical capsules; with one taken twice a day. This would make comparison fair.

We assessed the performance of the study in terms of recruitment and procedures.‘’

Dr Wilcock stated that the aim was to ’’measure any downsides (such as side effects) and explore for any benefits to the group receiving CLM. This will involve participants undergoing assessments of levels of inflammation in the body (by a blood test), how much muscle there is (a low-dose X-ray scan) and how they perform physically (grip strength and very simple ‘sit to stand’ and short walk exercise tests) before and after two months of treatment. We will also ask them to complete questionnaires about their quality of life and to tell us about their experiences of taking part in the study. We will also ask those declining to take part to identify any elements of the study which influenced their decision.’’

Sometimes, however, scientific research hits unexpected barriers. Such was the case with this project, which began in 2014 and ended in 2015.   

In a paper subsequently published in the scientific journal ‘Lung Cancer’, Dr Wilcock says:

‘’Over six months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45 patients or 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting.‘’

You can read the abstract of that report here. 

As Jackie Tebbs, the charity’s Head of Clinical and Research Projects, says: ‘’Dr Wilcock found it impossible to recruit the required number of participants with the qualifying criteria, so he called a halt to the project. That was very much to his credit. It was a difficult decision to make, but the right one.

‘’It was particularly disappointing because clarithromycin is a readily available, cheap drug, and it would have been wonderful to have something to control cachexia, which is a very challenging aspect of cancer. But that’s what research is all about – setbacks are part of advancing our knowledge base.  However, as Dr Wilcock suggested in his report, other drugs which don’t react adversely with drugs might yet provide an answer.’’

Lead researchers: Dr Andrew Wilcock / Location: University of Nottingham / Type of research: Patient experience