First-Line Treatment For Deadly Lung Cancer Not Superior

Ruzanna Harutyunyan's picture
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Lung cancer is one of the most common — and deadliest — cancers. Small cell lung cancer makes up about 10 percent to 15 percent of all lung cancers. Because of early metastatic spread, small cell lung cancer has very poor long-term survival with less than 10 percent of patients surviving two years after diagnosis.

Chemotherapy is the most common treatment for small cell lung cancer and many consider drugs containing platinum the most effective agents. However, a new evidence review calls that assumption into question.

"We found no significant difference in survival between platinum-based and non-platinum-based chemotherapy regimens," said lead review author Isuru Amarasena.

Amarasena and his colleagues are researchers at the University of Tasmania and the Prince Charles Hospital and District Health Service in Australia.

"Both platinum and non-platinum based regimens are commonly used in small cell lung cancer," Amarasena said. "Platinum-based regimens are generally considered to be the first-line treatment, but there is no definitive consensus about which treatment regimen is superior."

The review evaluated the findings of 29 studies conducted from 1982 to 2005. Of the 5,530 participants, half underwent chemotherapy with platinum-based agents and half with non-platinum agents. The studies lasted at least one or more years, with the longest study following patients for six years.

At six months, about 70 percent of patients in both groups were alive, while at 12 months about 36 percent had survived. At two years, only 10 percent of patients in both treatment groups were alive. Without any treatment, patients with small cell lung cancer have a median survival of only four to 12 weeks.

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The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

In almost 80 percent of the studies, treatment involved the platinum agent cisplatin, while it involved carboplatin in the remainder. The most common non-platinum agents used were etoposide, cyclophosphamide, vincristine and doxorubicin.

In addition to survival data, the researchers found that patients receiving the platinum-based regimens had greater frequency of nausea, vomiting, anemia and thrombocytopenia, a potentially serious reduction in blood platelets that can result in abnormal bleeding.

While the authors concluded that non-platinum regimens might therefore have a more acceptable risk-benefit profile, Amarasena stopped short of saying that they were better than standard platinum-based treatment regimens. "While our review won't necessarily change the role of platinum-based therapies in small cell lung cancer, it has highlighted the fact that non-platinum based therapies may be just as effective as platinum-based therapies," he said.

Surprisingly, few of the studies looked at quality of life, an important consideration because of poor long-term survival in both groups. "There is a need to incorporate quality of life assessments into similar trials in the future," Amarasena said.

Howard West, M.D., an oncologist and director of medical therapeutics at the Swedish Cancer Institute in Seattle, said that the review did not provide evidence that standard treatment of small cell lung cancer should change.

"Oncologists have no great love for platinum-based regimens, especially cisplatin," West said. "It can be a difficult drug to administer. But the fact that there has not been a change over many years is because the data has been far from compelling that there is a really competitive alternative out there. If you have a standard, you have to have a compelling reason to change that standard, and a comparison review like this does not do that."

West also said that many of the studies included in the review were too old to be relevant to current practices. "There is no clinical relevance to data from 10 years ago. We also have much better supportive treatments for side effects than we did 10 years ago. I would be more inclined to look at data from within the last five years. The [non-platinum] regimens in this review are not the regimens we would be thinking about using in our clinical practice right now."

While there have been few new developments in the treatments for small cell lung cancer, West said that some newer non-platinum alternatives that have been used in its treatment include the anticancer drugs topotecan, irinotecan and gemcitabine, among others.

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