Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib.

BACKGROUND: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity. METHODS: All patients had metastatic RCC with progression after treatment with sunitinib and/or sorafenib. Treatment consisted of erlotinib 150 mg orally once a day starting on day 1 and sirolimus 6 mg orally on day 8 followed by 2 mg daily, adjusted according to blood levels. RESULTS: A total of 25 patients were enrolled between July 2006 and March 2008. The median progression-free survival (PFS) was 12 weeks (95% CI 5.9-18.1) and median overall survival (OS) 40 weeks (95% CI 0-85.7). No confirmed complete or partial responses were observed, but stable disease >6 months was noted in 21.8% (95% CI 4.9-38.6) of patients. The most common adverse events were rash and diarrhoea. There was no correlation between erlotinib, OSI-420 (days 8 and 15) or sirolimus (days 15 and 29) blood levels and PFS or OS. CONCLUSIONS: The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.

Balancing ethical quandaries with scientific rigor: Part 2.

Traditional ethical concerns in research tend to focus on serious misconduct such as fabricating data and gross violations of informed consent. In this two-part article, we focused on some of the less serious and more subtle ethical quandaries, inherent and common in most social science research. It is our thesis that these issues are important and warrant more attention and careful thought than they have been accorded in the scientific literature and, perhaps, by investigators at large. In Part 2, we provided examples of how we, and others, dealt with some of these issues in actual studies. However, we also must emphasize the individual and reflective nature of confronting ethical issues in research. We found many benefits in using a team approach to address ethical dilemmas during implementation of our studies. Doing so kept everyone honest with themselves and each other, shared the burden of responsibility among team members for the decisions made, maximized the use of team members' strengths, and led to much better resolutions of the issues from both a scientific and an ethical perspective. Maintaining scientific rigor while balancing and deliberating about the ethical implications of decisions is a challenge for all research teams. It requires learning how to be vigilant and responsive when faced with the many subtle, but ever-present, scientific and ethical quandaries encountered when doing what is often assumed to be nonthreatening social research. There are no fixed, prescriptive rules for what to do in every study. Rather, a reflective process, considering the specific issues of each unique study, is required.

Community prostate cancer screening.

Health promotion and cancer prevention, including screening, are two important aspects of cancer care. However barriers exist to patients receiving recommended cancer screening procedures. One way to overcome these barriers is through the use of community cancer screening programs. This article presents a prototype of a community prostate cancer screening program. The program planning, staffing, promotion, cost and finance, and follow-up activities are explained. Furthermore, examples of communication tools and follow-up protocol, and results of 4 years of community screening programs are described. Recommendations for future community screening give insight for program improvement.