Irinotecan/Cisplatin Plus Simvastatin in Extensive Disease-Small Cell Lung Cancer (ED-SCLC)
Status:
Completed
Trial end date:
2010-05-01
Target enrollment:
Participant gender:
Summary
3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly referred to as the statins,
have proven therapeutic and preventative effects in cardiovascular diseases. Recently, there
are emerging interests in their use as anticancer agents based on preclinical evidence of
their antiproliferative, proapoptotic, anti-invasive, and radiosensitizing properties.
Inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by the statins interferes with the
rate-limiting step of the mevalonate pathway, leading to reduced levels of mevalonate and its
downstream products, many of which play important roles in critical cellular functions such
as membrane integrity, cell signaling, protein synthesis, and cell cycle progression.
Perturbations of these processes in neoplastic cells by the statins may therefore result in
control of tumor initiation, growth, and metastasis. The statins have demonstrated growth
inhibitory activity in cancer cell lines and preclinical tumor models in animals.
Simvastatin, a member of the statin family, profoundly impaired basal and growth
factor-stimulated SCLC cell growth in vitro and induced apoptosis. SCLC cells treated with
simvastatin were sensitized to the effects of the chemotherapeutic agent etoposide. Moreover,
SCLC tumour growth in vivo was inhibited by simvastatin. Therefore, the investigators will
conduct this phase II trial to evaluate the efficacy & toxicity of irinotecan/cisplatin plus
simvastatin in patients with chemo-naïve ED-SCLC.