Clin Cancer Res
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Over the last two decades, several approaches to multimodality therapy have been investigated in patients with advanced unresectable non-small cell lung cancer. These include induction chemotherapy and concurrent chemoradiotherapy. Both approaches have been shown to be superior to radiation therapy alone. ⋯ However, to date, no large randomized study evaluating a possible benefit from consolidation chemotherapy has been completed. In addition to evaluating optimal sequencing strategies of combined modality therapy, current investigations are also focusing on the integration of novel agents, including chemotherapeutic and targeted therapies. Currently ongoing trials involving novel approaches are reviewed here.
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Past lung cancer screening trials in the United States with chest X-ray and sputum cytology were not able to show any decrease in lung cancer mortality; however, these trials are over 20 years old. Recent follow-up of the Mayo Lung Project showed a better survival from lung cancer in the screened arm, but no difference in overall mortality, suggesting an overdiagnosis of nonfatal cancers. ⋯ All data available thus far on CT screening are from phase II proof-of-principle trials. The major limitations of CT screening, discussed here, include (a) a high rate of nodule detection: over 50% of participants will have at least one noncalcified nodule; (b) resulting follow-up CT scans, associated with increased costs; (c) cost and morbidity of biopsy or resection of benign noncalcified nodule (20-25% of such procedures in several trials); and (d) a small, but difficult to quantify, risk of cancer associated with multiple follow-up CT scans.
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The number of anticancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of molecules into the clinic requires improvement. The value of any preclinical model will ultimately depend on its ability to accurately predict clinical response. This review focuses on the major contributions of preclinical screening models to anticancer drug development over the past 50 years. ⋯ Europe has played a key role in the development of new anticancer agents. The two largest academic drug development groups, the European Organisation for Research and Treatment of Cancer and Cancer Research UK, have been collaborating with the NCI in the acquisition and screening of compounds since the 1970s. As with the drug development process internationally, rational pharmacodynamic approaches have more recently been adopted by these two groups.
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Review Randomized Controlled Trial Clinical Trial
Skeletal complications in patients with bone metastases from renal cell carcinoma and therapeutic benefits of zoledronic acid.
Bone metastases in patients with renal cell carcinoma are associated with a high risk of skeletal complications. Therefore, a subset analysis of a larger clinical trial was performed to determine the efficacy of zoledronic acid in renal cell carcinoma patients. Patients with bone metastases from solid tumors other than breast or prostate cancer (n=773) were randomized to receive zoledronic acid or placebo via 15-minute infusion every 3 weeks for 9 months. ⋯ Zoledronic acid significantly reduced the annual incidence of skeletal-related events by approximately 21% (mean 2.68 versus 3.38 events per year for placebo, P=0.014) and significantly reduced the risk of developing a skeletal-related event by 61% compared with placebo (risk ratio=0.394, P=0.008) by multiple event analysis. Median time to progression of bone lesions was also significantly extended with zoledronic acid treatment (P=0.014). Zoledronic acid is the first bisphosphonate to significantly reduce skeletal morbidity and significantly prolong time to bone lesion progression in patients with bone metastases from renal cell carcinoma.
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Up to one third of patients with renal cell carcinoma will present with metastatic disease, and 20 to 40% of those with clinically localized disease will eventually be found to have metastatic involvement. Prognosis continues to be guarded for this population, with a 2-year survival of only 10 to 30%. Although advances are being made in the medical management of renal cell carcinoma, the role of surgery in the treatment algorithm is also being additionally refined. ⋯ More controversial is the idea of cytoreductive nephrectomy as an adjunct to immunotherapy. Recent phase III trials indicate that nephrectomy may play an important role in management of metastatic renal cell carcinoma in conjunction with cytokine-based immunotherapy. Nephrectomy is also an essential component of tumor-based vaccine and adoptive immunotherapy protocols and may play a role in other novel therapies.