First-Line Chemo for Small-Cell Lung Cancer is Not Superior to Second-Line

Nick Mulcahy

October 07, 2008

October 7, 2008 — A new meta-analysis of chemotherapies for small-cell lung cancer (SCLC) indicates that first-line platinum-based regimens do not offer a statistically significant benefit in survival or overall tumor response, compared with second-line nonplatinum-based regimens.

The study appears in the latest issue of the Cochrane Library, a publication of the Cochrane Collaboration. However, according to critics of the study, the analysis adds little to clinical practice.

"The problem with this paper is that it is not relevant to current clinical practice. The fact is that there is no good example of a nonplatinum regimen that I can use with my patients," said Athanassios Argiris, MD, medical director of the Aerodigestive Cancers Program at the University of Pittsburgh Cancer Institute, in Pennsylvania, in an interview with Medscape Oncology.

The meta-analysis makes a comparison that is dated and outmoded, suggested Dr. Argiris.

"Most of the studies reviewed here are from the 1980s and 1990s," he said. He explained that the most important studies comparing platinum and nonplatinum regimens date from the early 1990s, but that clinical trials no longer compare the 2. "No recent large-scale phase 3 trials even make this comparison," he added.

Dr. Argiris said that the standard of care has evolved into 1 of the 2 platinum agents, cisplatin or carboplatin, used in combination with nonplatinum etoposide. To date, nonplatinum regimens have not been proven superior to this standard of care, which now has a long "track record."

Another critic, Howard West, MD, director of medical therapeutics at the Swedish Cancer Institute, in Seattle, Washington, said that the review did not provide evidence that the standard treatment for SCLC should change.

"If you have a standard [such as platinum-based regimens], you have to have a compelling reason to change that standard, and a comparison review like this does not do that," he said.

Outdated Nonplatinum Agents Weaken Analysis

The new review includes a total of 29 trials involving 5530 patients (2764 received platinum-based therapy; 2766 received nonplatinum-based therapy), and was lead by Isuru Amarasena, from the School of Medicine at the University of Tasmania, in Hobart, Australia.

Cisplatin is the most common nonplatinum agent in the trials (79%), and carboplatin is used in the remaining studies (21%).

The most common nonplatinum agents used in the 29 clinical trials were etoposide (82%), cyclophosphamide (75%), vincristine (62%), and doxorubicin (62%).

Therein lies the problem, stated Dr. West. "The [nonplatinum] regimens in this review are not the regimens we would be thinking about using in our clinical practice right now," he said.

Some newer nonplatinum alternatives for SCLC include topotecan, irinotecan, and gemcitabine, he said.

Both Dr. Argiris and Dr. West noted that platinum-based regimens have been the standard of care for a considerable amount of time. "Small-cell lung cancer treatment has not changed much at all since the 1990s," said Dr. Argiris. The stasis in SCLC treatment is in contrast to the improvements in the treatment of non-SCLC. "Non–small-cell lung cancer accounts for the great majority of lung cancer cases. Small-cell lung cancer has been decreasing in prevalence for some time and is now about 15% of lung cancer cases," he explained.

Currently, the research challenges for treating SCLC lie outside the framework of platinum- vs nonplatinum-based regimens, said Dr. Argiris. "The current challenge in small-cell lung cancer treatment is not to identify a nonplatinum regimen. The challenge is to identify either the optimal agent to add to platinum or a third agent to add to the standard of care, a platinum [cisplatin or carboplatin] and etoposide," he said.


The meta-analysis indicates that there is no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months, or 24 months.

However, platinum-based treatment regimens have a significantly higher rate of complete response or remission of the cancer. Nevertheless, for overall tumor response (complete and partial remission), there is no significant difference.

In the analysis, platinum-based chemotherapy regimens also had higher percentages of adverse events, including nausea and vomiting, anemia, and thrombocytopenia toxicity.

However, Dr. West noted that this finding was in need of qualification because supportive treatments for adverse effects are now "much better."

Quality-of-Life Data Should Improve

In the review, at 6 months, about 70% of patients in both treatment groups were alive, whereas at 12 months, about 36% were alive. At 2 years, only 10% of patients in both treatment groups were alive. Still, without any treatment, patients with SCLC have a median survival of only 4 to 12 weeks, write the authors.

Because SCLC is an aggressive cancer, and because early metastasis (both local and distant) is common and long-term survival is poor, the meta-analysis authors highlight the lack of quality-of-life data in past 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," they write. It would be beneficial for future trials in this area to include a quality-of-life assessment, they add. Dr. Argiris agreed that the quality of life of patients has "not been studied enough."

The researchers have disclosed no relevant financial relationships.

Cochrane Library. 2008;4:1-112.