More aggressive chemotherapy is better for older lung cancer patients, according to The Daily Telegraph. The newspaper says that doctors' and patients' desire to be cautious can often result in patients being given single-drug therapy for advanced lung cancer, but that new research has shown that using two drugs at a time could enable patients to live months longer.
The news is based on a trial that compared a combination therapy with two chemotherapy drugs against single-drug therapy for patients aged over 70 with advanced lung cancer. It found that average overall survival was 10.3 months with the combination therapy and 6.2 months for monotherapy patients – a difference of around four months. There were more toxic side effects with the combination therapy, but patients in both groups rated their quality of life similarly.
NICE guidelines already suggest that advanced non-small-cell lung cancer should be treated with combination therapies when they can be tolerated, irrespective of age. Single therapy is offered to people who cannot tolerate the combination therapy. Doctors will make this decision on a case-by-case basis, and this research does shed some light on the issue.
Where did the story come from?
The study was carried out by researchers from the University of Strasbourg Hospital and other university hospitals in France. It was funded by Intergroupe Francophone de Cancérologie Thoracique and France’s National Cancer Institute. The study was published in the peer-reviewed medical journal The Lancet.
The data from the research study was reported well by The Daily Telegraph. However, it is not clear from this study how relevant the study is to the UK, as it would take separate research to assess how many UK patients over the age of 70 are currently treated with the single or double drug treatments.
What kind of research was this?
This was a randomised control trial of people between the ages of 70 to 89 with advanced lung cancer. The trial compared chemotherapy using a combination therapy of two drugs called carboplatin and paclitaxel against a chemotherapy regime where the patients received only one type of drug (either vinorelbine or gemcitabine). The researchers measured how these treatment regimens affected overall survival.
What did the research involve?
Between April 2006 and December 2009 researchers recruited lung cancer patients from 61 medical centres (university hospitals, cancer centres and community hospitals) in France. The participants were aged between 70 and 89 and had advanced inoperable lung cancer which had spread to other parts of the body. The type of lung cancer the participants had was non-small cell lung cancer (NSCLC). The study required that the participants had a life expectancy of at least 12 weeks and adequate kidney, blood and liver function to tolerate the treatment.
The study excluded people who had another cancer that required treatment within the last five years, any previous chemotherapy or nerve damage. The researchers also excluded people who had other conditions/complications that impaired administration of chemotherapy or who had breathing difficulties that meant that they needed chronic oxygen delivery.
Another condition for eligibility was that participants had to have a performance status of two or below. A performance status of two means that people are still able to walk and take care of themselves but cannot perform work activities and may spend half of their waking hours resting. A score of below two would indicate that people have greater function.
The eligible participants were randomly assigned to receive one of the following:
- Combination therapy of carboplatin and paclitaxel. Both of these drugs are administered intravenously. Carboplatin was delivered on the first day of a treatment cycle and paclitaxel on days 1, 8 and 15. Cycles were repeated every four weeks (three weeks of treatment plus one week without). It was planned that participants would be given no more than four cycles.
- Single-drug therapy with either vinorelbine or gemcitabine. Participants were treated with one of these drugs on the first and eighth days. The choice between vinorelbine and gemcitabine was made by each centre at the beginning of the study. Cycles were repeated every three weeks (two weeks of treatment plus one week without). It was planned that the maximum number of cycles would be five. If the participants showed disease progression or were intolerant to the drugs, the treatment was withdrawn and replaced with a daily dose of the drug erlotinib (150mg) until further disease progression or excessive toxic effects were seen.
The main outcome the researchers were interested in was overall survival, which was defined as the time from randomisation to death due to any cause. They were also interested in “progression-free survival” (time from randomisation until progression of the cancer or death), side effects of the treatment and quality of life.
What were the basic results?
The median age of participants was 77. One hundred and eighteen people (26.1% of those initially recruited) had a performance status score of two or less at baseline. The follow-up period varied between 8.6 and 45.2 months for individual patients, with a median follow-up of 30.3 months. The baseline characteristics between the combination therapy and the single-drug therapy were similar, except that more patients in the single-drug therapy group had already lost more than 5% of their weight in the three months before randomisation. As a consequence, this group had a lower body mass index at baseline than the combination group.
In total, 226 participants were assigned to receive single-drug therapy. Sixty-two received vinorelbine and 164 received gemcitabine. Some 225 participants received the combination therapy. The median number of treatment cycles in each group was four.
The researchers performed several analyses comparing combination therapy against single-drug therapy:
- Median overall survival time was higher in the combination therapy group than the single-therapy groups – 10.3 months vs 6.2 months (hazard ratio 0.64; 95% confidence interval [CI] 0.52 to 0.78; p<0.0001).
- All-cause mortality within the first three months of treatment (termed “early death”) was lower in the combination therapy group compared to the single-therapy group - 16.4% vs 26.4% (p=0.0408).
- One-year survival rate was 44.5% in the combination group and 25.4% in the single-drug group (95% CI 37.9 to 50.9 vs 95% CI 19.9 to 31.3).
- Progression-free survival was also longer in the combination treatment group compared to the single-therapy group.
The researchers also examined the risk of several side effects. They found that people receiving the combination therapy were more likely to have loss of a type of white blood cells called neutrophils, have anaemia and have nerve damage in their sensory nerves than people receiving single-drug therapy.
The participants completed quality of life questionnaires at weeks 6 and 18. At the sixth week, the overall quality of life scores were similar between the two groups. However, more patients in the single-therapy group had pain (30.2% vs. 18.7%) and shortness of breath (47.4% vs, 36.8%). More people in the combination therapy group had diarrhoea (18.4% vs 8.8%). At week 18, again the global quality of life score was similar between the two groups, but fatigue and role functioning were worse in the combination group than the single-therapy group.
How did the researchers interpret the results?
The researchers said therapy combining “carboplatin and weekly paclitaxel yielded better results than did monotherapy [single-drug treatment] with either vinorelbine or gemcitabine, in terms of overall survival, progression-free survival and response rates in elderly patients with advanced non-small-cell lung cancer”.
This randomised trial demonstrates that combination therapy may be beneficial to some elderly people with non-small cell lung cancer. Although the study has shown its benefits in a specific group - older people with inoperable lung cancer who were still able to function fairly well - doctors would still need to judge how well each person would be able to tolerate this treatment on a case-by-case basis. This would be especially true in elderly people, who may have other conditions alongside their cancer.
Likewise, the study population had non-small cell lung cancer which was advanced. Different stages of cancer may require different treatment plans, as combination treatment may not be as well tolerated or effective in these people.
NICE guidelines already suggest that for advanced non-small-cell lung cancer, carboplatin plus paclitaxel (or other forms of combination therapy) should be used, irrespective of age. Single therapy is offered to people who cannot tolerate the combination therapy.
This trial was useful as it provides intelligence on the use of combination therapy in an older population, which may not be as commonly represented in clinical trials. However, it is not clear from this study how many elderly people with lung cancer are treated with monotherapy or combined therapy outside the context of this study, and further research may be needed to assess its use in everyday practice.