December 5, 2013 -- A recent study featured in the latest issue of The Oncologist shows that active smoking greatly diminishes patients’ chances of responding to chemotherapeutic treatment for renal cell carcinoma (RCC). The research team, jointly led by Dr. Michael Carducci from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD and Dr. Daniel Keizman from the Sackler School of Medicine at Tel Aviv University, conducted a retrospective analysis exploring the association of various risk factors for RCC with patient response rate and survival following sunitinib treatment.
RCC is the most common type of malignancy of the kidney and the tenth most common cause of cancer-related death among men in the US. Approximately 30% of patients with RCC present with metastases, and 40% of those treated for a localized tumor eventually show recurrence. Sunitinib, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as a first-line treatment for this disease; however, its efficacy is limited, and tumors will often progress post treatment. The researchers utilized data from 278 metastatic RCC patients who had undergone sunitinib treatment at 7 different institutions in the US and Israel and assessed known risk factors for the disease, including smoking, obesity, and diabetes, all of which have been associated with poor therapeutic outcome in various cancers. Concordant with RCC epidemiology, the median age of the participants was 63 and about two-thirds of them were men. While about half of the patients were never smokers, more than 20% were active smokers, and the remainder had some history of smoking. Nearly a quarter of the patients were obese, more than a quarter were diabetic, and more than half of them had hypertension prior to sunitinib treatment.
After a median follow-up period of 55 months, imaging evaluations revealed a complete response in 3% of patients, a partial response in 36%, stable disease in 39% and progression in 22%. Nine months was the median progression-free survival time, and 22 months was the median overall survival time. Ultimately, at follow up, nearly 90% of patients had progressed and 73% had died. The authors used both univariate and multivariate statistics to determine whether individual risk factors modified the survival or response rates in these patients.
In a multivariate model, never smokers were significantly less likely to have disease progression upon follow up compared with active smokers. Likewise, patients with clear cell histology, absence of liver metastases, low pre-treatment neutrophil-to-lymphocyte ratio (NLR), and presence of sunitinib-induced hypertension were all independently associated with a more favorable response to sunitinib treatment. As expected, active smokers had significantly worse progression-free survival compared with never smokers (4 months versus 12 months, respectively). Non-clear cell histology, high pre-treatment NLR, and failure to use angiotensin system inhibitors were all significantly associated with poorer progression-free survival. Active smoking was also significantly associated with poor overall survival compared to never smoking (11 months versus 25 months), as was a high NLR and absence of sunitinib-induced hypertension. An additional analysis in which variables were iteratively eliminated from the model showed some discrepancies among other variables; however, the association between active smoking and survival remained strong. Additionally, a subgroup analysis comparing active smokers and a cohort of non/past smokers matched on age, gender, and a number of clinical characteristics revealed that non/past smokers had a dramatically lower risk of showing progression on follow-up and had more than double the rate of progression-free and overall survival.
Previous studies have shown that RCC patients who have smoked tend to have more severe clinical features and worse survival compared with never smokers, potentially due to increased inflammation, oxidative tissue damage, or immune suppression, any of which can promote tumor progression. This study supports these findings and extends their scope to include patients who have undergone one of the most efficacious treatments for the disease. While it may seem surprising, a recent survey study found that less than half of cancer patients who were active smokers claimed to have quit smoking after being diagnosed with cancer. Perhaps more surprising is that only 62% of these patients were advised by their clinicians to quit. According to Drs. Keizman and Carducci, “Ongoing smoking may negatively impact the response to therapy as well as the time period without disease progression and the longevity of patients. Thus, clinicians should consider advising patients to quit smoking at initiation of therapy for metastatic disease.”
Dr. Martin J. Murphy, Jr., Executive Editor of The Oncologist, explains the study’s impact: “Smoking is a known risk factor for the development of kidney cancer. This international study demonstrates that ongoing smoking during chemotherapy may impede a patient’s response to therapy, resulting in a decrease in the longevity of those patients who continued to smoke. The diagnosis of cancer has profound consequences. It may, used properly, become an excellent ‘teachable moment’ for clinicians to advise their patients to quit smoking at the initiation of therapy for metastatic kidney cancer. The length of their lives could depend on it.”
The full article, titled “Active Smoking May Negatively Affect Response Rate, Progression-Free Survival, and Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib,” can be accessed at www.TheOncologist.com.
About The Oncologist
Established by oncologists to help physicians better manage their practices in an ever-changing environment, The Oncologist® is the official journal of the Society for Translational Oncology (STO). Now in its 18th year, this internationally peer-reviewed journal focuses on clear and concise interpretation addressing the multimodality diagnosis, treatment, and quality of life of the cancer patient. Each issue is meant to impact the practice of oncology and to facilitate significant communication in the introduction of new medical treatments and technologies. For more information, visit www.TheOncologist.com.
About AlphaMed Press: Established in 1983, AlphaMed Press, with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (www.StemCells.com), which celebrated its 31st year in 2013, is the world’s first journal devoted to this fast paced field of research. THE ONCOLOGIST® (www.TheOncologist.com), entering its 18th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (www.StemCellsTM.com), in its second year, is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.
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