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, we will conduct this phase II trial to evaluate the efficacy & toxicity of irinotecan/cisplatin plus simvastatin in patients with chemo-naïve ED-SCLC.
Primary Outcome Measures:
- 1-year survival & overall survival [ Time Frame: the first day of treatment to death or last survival confirm date ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Tumor response rate [ Time Frame: the ratio between the number of responders and number of patients assessable for tumor resonse ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: the first day of treatment to the date that disease progression is reported ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: the first date of treatment to 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
Estimated Enrollment: |
61 |
Study Start Date: |
April 2006 |
Estimated Study Completion Date: |
February 2008 |
Estimated Primary Completion Date: |
February 2008 (Final data collection date for primary outcome measure) |
1: Experimental
|
Drug: Irinotecan
Irinotecan 65mg/m2/iv over 90min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.
Drug: Cisplatin
Cisplatin 30mg/m2/iv over 30min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.
Drug: Simvastatin
simvastatin 40mg/QD, PO, daily, every 3 weeks
|
Cisplatin-30 mg/m2 on day 1 and 8 repeat q 3 weeks Irinotecan-65 mg/m2 on day1 and 8 repeat q 3 weeks Simvastatin 40 mg per day orally from D1 of cycle 1
Treatment will be continued until disease progression, unacceptable toxicity, or patients' refusal.