Using cholesterol-lowering drugs in combination with chemotherapy does not improve the outcomes of patients with small-cell lung cancer, according to results from the largest randomized trial ever of statin therapy in cancer patients.
Researchers argued that current or planned trials assessing the use of statins in cancer treatment should be reconsidered in light of such compelling data.
The study, “Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR),” was published in the Journal of Clinical Oncology.
Small-cell lung cancer (SCLC), which accounts for 15 to 20 percent of all new lung cancer cases, is associated with low survival — a median of eight to 14 months.
A number of studies have indicated that statins, inexpensive cholesterol-lowering drugs used to prevent heart attacks or strokes, can inhibit the growth and trigger the death of some tumor cells. They include SCLC, mesothelioma, pancreatic cancer, and breast cancer tumors.
Several large prospective cohort studies have indicated that statin use leads to major improvements in cancer incidence, recurrence, and mortality in multiple cancer types. But the studies were all observational, and none established the best dose for statin effectiveness.
To try to clarify whether taking statins during chemotherapy is beneficial, a team from Imperial College London and University College London (UCL) conducted the LUNGSTAR Phase 3 trial. The randomized, double-blind, placebo-controlled study assessed the safety and effectiveness of adding the statin pravastatin to a first-line standard chemotherapy in patients with small-cell lung cancer.
The study included 846 patients from 91 hospitals in the United Kingdom. Researchers conducted it at the Cancer Research UK & UCL Cancer Trials Center.
Participants were randomized to receive pravastatin or a placebo in combination with a typical chemotherapy treatment — up to six cycles of etoposide plus Platinol or Paraplatin (carboplatin) — until the disease progressed or the patient was unable to tolerate the treatment.
While the study showed that patients experienced no adverse effects from the statin, they did not benefit from it, either. Overall survival for patients taking pravastatin was 10.6 months, versus 10.7 months for the placebo group. Similarly, median progression-free survival was 7.7 months for the pravastatin group, versus 7.3 months for the placebo group.
“It’s becoming increasingly common for patients with increased cholesterol to take statins, and many cancer patients will be or have been prescribed these drugs entirely separately from their cancer treatment,” the study’s lead author, Professor Michael Seckl, said in a press release.
“There’s no reason for people to stop taking statins to manage their cholesterol, but it’s extremely unlikely, for patients with small cell lung cancer, that taking statins will make any difference to their cancer treatment outcome,” said Secki, a member of the Imperial College Faculty of Medicine. “Because all statins work in a similar way to lower cholesterol, it’s relatively unlikely that statins other than Pravastatin would have a different, more beneficial effect.”
The team now plans to assess how statins work at the cell level. They believe more large clinical trials assessing statins’ effectiveness in the same cancers are unnecessary. But they do not rule out the possibility that statins could work in other cancer types.
“It is possible that ongoing statin trials of other types of cancers might find a benefit, and so it would be interesting to see their findings when available,” said the study’s senior author, Professor Allan Hackshaw, deputy director of the Cancer Research UK & UCL Cancer Trials Center. “However, I think researchers should consider carefully whether to start a new statin trial as part of cancer treatment, without results from further large studies like ours.”