A comparison of platinum-based and non-platinum-based chemotherapy regimens for the treatment of small cell lung cancer

Review question

Do patients with small cell lung cancer (SCLC) who receive platinum-based chemotherapy treatment live longer than those who receive non-platinum-based chemotherapy treatment?

Other questions include: do these patients also respond better to treatment, experience fewer side-effects and have a better quality of life?

Background

SCLC is a type of cancer that originates in the lungs. It is a very aggressive form of cancer that tends to grow and spread throughout the body quickly. As a result, chemotherapy is often the first type of treatment used for this type of cancer. Another type of treatment used for SCLC is radiotherapy, which is often given to the lung or to the brain.

A combination of a number of chemotherapy drugs used together is called a ‘chemotherapy regimen’. Currently, there are two main chemotherapy regimens used for treating SCLC:

• platinum-based chemotherapy regimens – containing a chemotherapy drug known as a “platinum agent” in combination with other chemotherapy drugs and;

• non-platinum-based chemotherapy regimens – containing other chemotherapy drugs without a “platinum agent”.

Over the past years, many studies have been done comparing the use of platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens in SCLC.

We carried out a study, called a meta-analysis, which included patients with SCLC who took part in randomised controlled trials comparing platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens.

Study characteristics

We searched for studies up to 1st August 2014. A total of 32 studies were part of this review and included 6,075 patients in total. The studies were carried out in many different countries throughout Europe, Asia and North America. The studies were conducted between 1981 and 2014.

Key results

The review showed that patients who received platinum-based chemotherapy were not any more likely to be alive at 6 months, 12 months and 24 months after treatment compared with patients who received non-platinum-based chemotherapy.

Platinum-based chemotherapy, however, showed higher rates of complete tumour response (the complete disappearance of tumours, at least for a period of time after treatment) compared to non-platinum-based chemotherapy. Platinum-based chemotherapy also caused some more side effects, including nausea and vomiting, and low platelets.

Only four studies looked at quality of life but because they each used different methods to measure the effects, their results could not be combined. However, in each study there was no difference in the quality of life between the platinum-based chemotherapy group and the non-platinum-based chemotherapy group.

Authors' conclusions: 

Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.

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Background: 

Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness.

Objectives: 

To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life.

Search strategy: 

We searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources.

Selection criteria: 

All randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm.

Data collection and analysis: 

We used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually.

Main results: 

A total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.

There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis.

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