SUMMARY: The American Cancer Society estimates that approximately 137,000 new cases of colorectal cancer will be diagnosed in the United States in 2014 and over 50,000 are expected to die of the disease. Data from 60 epidemiological studies enrolling more than 26,000 ColoRectal Cancer (CRC) patients have shown that higher consumption of milk and dairy products reduces the risk of colon cancer and high Calcium intake reduces the risk of CRC. In vivo and in vitro studies have confirmed these findings.
Milk, in addition to being a rich source of dietary Calcium and Vitamin D is a primary dietary source of conjugated linoleic acid which has been shown to inhibit colon cancer cell growth. Dairy products also provide other beneficial components such as butyric acid, lactoferrin and fermentation products. The impact of milk and dairy products on CRC survival however has remained unclear. The Cancer Prevention Study – II Nutrition Cohort is a prospective study of cancer incidence that began in 1992. Participants in this study (N=184,000) were provided a self administered questionnaire and baseline information about their dietary habits (including dietary Calcium and Vitamin D, as well as Calcium, Vitamin D and multivitamin supplements), physical activity, body size, cancer screening and early detection, etc. was collected and follow up questionnaires were sent every other year to update information and learn about new cancer diagnosis. Patients were followed up until June 2009 and by the end of this period, 3,832 individuals who had no history of disease at baseline had been diagnosed with invasive colon or rectal cancer. After excluding patients with distant metastatic disease, 2,284 patients were included in this analysis and among them, 1,111 patients reported post diagnosis diet. The primary outcome of this study was all cause mortality and the secondary outcome was mortality resulting from colorectal cancer. Using standard statistical models, the investigators noted that post CRC diagnosis total Calcium intake and milk intake, was inversely associated with all-cause mortality and significantly reduced CRC specific mortality.
This benefit however, was not seen with Vitamin D intake. Also of interest, pre-diagnosis Calcium, Vitamin D, and dairy product intakes did not influence mortality outcomes. The authors concluded that higher post-diagnosis intakes of total Calcium and milk may be associated with lower risk of death among patients with non-metastatic ColoRectal Cancer. In a more recent publication, it has been reported that there is a strong association between plasma level of 25-hydroxyvitamin D (25-OHD) and CRC specific mortality, with better outcomes in patients with Stage I-III CRC, who had higher plasma levels of 25-OHD (Zgaga L, et al. J Clin Oncol 2014;32:2430-2439). With 30-35% of the malignancies attributed to dietary habits, the onus is therefore on the treating physicians to provide nutrition counseling during and after cancer treatment and is not to be ignored. Yang B, McCullough ML, Gapstur SM, et al. J Clin Oncol 2014;32:2335-2343
Tag: General Medical Oncology & Hematology
NCCN Guidelines for Survivorship Expanded to Address Two Common Conditions
SUMMARY: The National Comprehensive Cancer Network (NCCN) has expanded its Survivorship Guidelines to include cancer-associated cognitive impairment and Chemotherapy Induced Peripheral Neuropathy. The later is a component of the Adult Cancer Pain section. Dr. Urba discussed the management of Chemotherapy Induced Peripheral Neuropathy at the NCCN 19th annual conference. Approximately 20%-40% of the patients suffer from Chemotherapy Induced Peripheral Neuropathy, which can result in premature discontinuation of treatment. Further, this adverse event in a significant number of patients can persist indefinitely and can be disabling, thus impacting their activities of daily living.
The following chemotherapeutic agents are associated with varying degrees of peripheral neuropathy – Platinum compounds (Cisplatin, Carboplatin and Oxaliplatin), Taxanes (Paclitaxel, Docetaxel), Immunomodulatory agents (Thalidomide, Lenalidomide), Other Microtubule inhibitors (Vincristine, Ixabepilone) and Proteosome Inhibitors (Bortezomib). It may be necessary to screen and rescreen patients for neuropathic pain, as patients may not be forthcoming with this complaint. Management of Neuropathic pain may include systemic treatment with adjuvant analgesics, topical therapies and psychosocial support. The management of Chemotherapy Induced Peripheral Neuropathy has mostly been extrapolated from validated studies on diabetic neuropathy. The first line treatment for Chemotherapy Induced Neuropathic Pain includes antidepressants and anticonvulsants, which if not effective on their own, can be combined with opioids. TriCyclic Antidepressants (TCA’s) such as Amitriptyline and Nortriptyline (PAMELOR®) can be considered as first line choice for appropriate patients, although its mechanism of action is uncertain and 20% of the patients discontinue therapy because of adverse effects.
Patients may be able to better tolerate these agents if started at a lower dose and dose titrated slowly every three to five days. Peripheral neuropathic pain has been attributed to an unbalanced release of norepinephrine and serotonin from the neurons. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI’s), including Venlafaxine (EFFEXOR®) and Duloxetine (CYMBALTA®), are better tolerated and have fewer drug interactions than TCA’s. EFFEXOR® in one study significantly relieved Oxaliplatin induced neuropathic pain in more than two thirds of the patients when compared to placebo and a third of the patients had complete pain relief. There is however limited evidence showing a beneficial role of Selective Serotonin Reuptake Inhibitors (SSRI’s) such as Citalopram (CELEXA®) and Paroxetine (PAXIL®) for neuropathic pain. As a note of caution, SNRI’s such as EFFEXOR® and CYMBALTA®, can interact with Tamoxifen, prescribed to patients with breast cancer, preventing Tamoxifen from converting to its active form. The dose of antidepressants needed to alleviate neuropathic pain is not dependent on antidepressant activity and may be lower than that recommended for treatment of depression. The newer anticonvulsants such as Gabapentin (NEURONTIN®), Pregabalin (LYRICA®) are preferable first line agents for the treatment of neuropathic pain rather than traditional, older agents such as Carbamazepine (TEGRETOL®), Phenytoin (DILANTIN®) and Valproate (DEPAKOTE®), as the newer agents are associated with fewer drug interactions. The newer agents bind to the alpha2-delta subunit of the calcium-sensitive channels, modulating neurotransmitter release. Of the newer agents, NEURONTIN® (Gabapentin) is not protein bound and is excreted unchanged in the urine and therefore has fewer drug interactions. If opioids are a consideration for neuropathic pain relief, the lowest dose is recommended. Topical therapies for neuropathic pain have the advantage of controlling pain without systemic side effects. It therefore can be combined with systemic treatment. Lidocaine 5% patches (LIDODERM®) block neuronal sodium channels whereas Capsaicin cream (ZOSTRIX®) stimulates the C fibers to release and subsequently deplete substance P, there by blocking pain signaling to the brain. Diclofenac gel 1% when applied once a day, concentrates in the dermis and has less gastrointestinal side effects and may be beneficial for neuropathic pain. A combination of Ketamine 1% and Amitriptyline 2% cream applied topically has also been promising in a small study. Patients experiencing refractory pain may benefit with the use of Transcutaneous Electrical Nerve Stimulation (TENS), although referral to the pain clinic may be appropriate. Psychosocial support utilizing a team of specialists and social workers/counsellors, should be an integral part of pain management. Kvale E and Urba SG. National Comprehensive Cancer Network (NCCN) 19th Annual Conference, March 13 – 15, 2014; Hollywood, Florida
The ASH Choosing Wisely® campaign five hematologic tests and treatments to question
SUMMARY: CHOOSING WISELY® is a quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States such as the American Society of Hematology (ASH). This organization was established to improve quality of medical care, after it was noted that about 25% of the tests ordered at the time of hospital admission and 65% of the tests ordered on subsequent days were avoidable. Further, there is ample evidence to suggest that reducing unneeded investigations can decrease costs, increase patient satisfaction and quality of care. CHOOSING WISELY® has challenged medical societies to identify 5 tests, procedures or treatments, within each specialty's clinical domain, that are offered to patients, despite the lack of evidence demonstrating its benefit. The goal is to make positive changes in the actual delivery of patient care. The ASH identified 5 tests and treatments that practicing hematologists should give due consideration to, that in some situations are not evidence based and which in certain cases are associated with risks that outweigh the benefits and are not cost efficient.
Gaps in Pre-rituximab Hepatitis B Screening An Institutional Experience
SUMMARY:The Centers for Disease Control and Prevention (CDC) estimates that there are 800,000 -1.4 million individuals with Chronic Hepatitis B infection in the United States. Reactivation of HBV is a major concern in cancer patients who may be on chemotherapy or other immunosuppressive therapies, with the incidence of HBV reactivation ranging from 40%-60% in those who are positive for Hepatitis B surface antigen (HBsAg). HBV reactivation is preventable with prophylactic antiviral therapy, failing which it can result in delays in cancer treatment as well as potentially fatal outcomes.
The CDC updated their recommendations in 2008 and recommended HBV screening for patients receiving cytotoxic chemotherapy or immunotherapy. The American Society of Clinical Oncology in 2010 rendered a Provisional Clinical Opinion (PCO) suggesting that there was insufficient evidence to recommend routine screening for HBV in cancer patients,but screening may be considered for patient populations at high risk or for those who are to receive highly immunosuppressive therapies including anti-CD20 monoclonal antibody therapy such as Rituximab (RITUXAN®). To evaluate compliance with these recommendations, the authors in this study retrospectively reviewed charts of patients with Low grade Non Hodgkins Lymphoma at a teritiary care center and documented the various studies performed, as a part of the pretreatment workup, between January 2005 and December 2011. They noted that only 19% of the total patients and 25% of the patients who received RITUXAN® had HBV screening done. The authors concluded that this was a significant deviation from the recommended guidelines and these findings resulted in the implementation of stricter measures for HBV screening at this teritiary care center. Screening for HBV should include testing for Hepatitis B surface antigen (HBsAg), Antibody to Hepatitis B core antigen (anti-HBc) and Antibody to Hepatitis B surface antigen (Anti-HBs). Patients positive for HBsAg and anti-HBc as well as those who are negative for HBsAg and positive for anti-HBc, should have testing for HBV viral load using serum HBV DNA and those without active disease should receive prophylactic antiviral therapy and be closely monitored for HBV reactivation. Prophylaxis is usually started one week before initiating chemotherapy and continued for at least 6 months after completion of chemotherapy, although the actual duration of prophylactic antiviral therapy remains unclear. If HBV reactivation is noted, chemotherapy should be immediately discontinued. Given the prevalence of chronic Hepatitis B in the United States, screening for HBV should become a routine part of pretreatment evaluation in cancer patients. Abbi KK, Gorris M, Skeel RT. Am J Ther. 2013;June 28.
SYLVANT® (Siltuximab)
The FDA on April 23, 2014 approved SYLVANT® for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV-) -negative and human herpes virus -8 (HHV-8) -negative. SYLVANT® injection is a product of Janssen Biotech, Inc.
The Role of Human Papillomavirus in Nongenital Cancers
SUMMARY: Human Papilloma Virus (HPV) is a double stranded DNA virus and is the most common sexually transmitted infection in the U.S. It was responsible for over 25,000 cancers between 2004 and 2007 in the U.S. and the incidence is rapidly increasing due to changes in sexual practices. Even though the low risk HPV types such as HPV-6 and HPV-11 have been well known to cause benign lesions such as condylomata (genital warts), low grade squamous intraepithelial lesions of the cervix and laryngeal papillomas, the high risk HPV types such as HPV-16 and HPV-18 have been of major concern because of their malignant potential. Since the implication of HPV-16 and HPV-18 in cervical cancer dating back to the early 1990’s, these HPV subtypes have also been found responsible for 45-90% of oropharyngeal cancers and 90% of anal cancers. HPV in tumor tissue can be detected by immunohistochemistry testing for P16 expression and confirmed with HPV DNA PCR. 
Chronic immunosuppression as seen in patients with HIV and in patients undergoing solid organ transplantation, may increase the risk for HPV infections. Patients with HPV associated oropharyngeal cancer typically are younger males, tend not to smoke or drink and present with poorly differentiated, non keratinizing tumors with basaloid morphology, compared to those with HPV negative tumors. Clinical characteristics of HPV positive oropharyngeal cancer patients with best outcomes include, those with fewer than 10 pack year smoking history and lower tumor stage. Several retrospective trials as well as some small prospective studies have shown that HPV positive oropharygeal cancers when treated with chemoradiation have significantly higher response rates, progression free survival, overall survival and better local and regional disease control. In the TAX 324 randomized phase III trial, patients received induction treatment with 3 cycles of TAXOTERE®, Cisplatin and 5-Fluorouracil (5-FU) or Cisplatin and 5-FU followed by chemoradiation with concurrent PARAPLATIN® (Carboplatin). Even though the 3 drug induction treatment group had superior outcomes compared to those who received 2 drug induction regimen in the intent to treat population, on retrospective analysis, patients with HPV positive oropharyngeal cancer had a significantly longer 5 year progression free survival (78% vs 28%) and overall survival, with an 80% reduction in mortality (HR=0.20, P<0.0001), compared to HPV negative patients, regardless of induction treatment. Other studies have shown that HPV positive patients who undergo surgery alone for oropharyngeal cancer do not appear to reap these favorable benefits, suggesting that the improved prognosis in the HPV positive patients with oropharyngeal cancer is related to chemotherapy and radiation. It also appears that HPV positive patients with oropharyngeal cancer have a better prognosis with treatment when their tumors are P53 wild type and express P16. With regards to EGFR and P16, there appears to be an inverse correlation between P16 and EGFR expression and patients with tumors expressing P16 and not EGFR have a significantly higher 5 year disease free and overall survival compared to those whose tumors overexpress EGFR but not P16. This information may have significant therapeutic implications and studies are underway trying to address this group of patients with targeted and less intense treatments. It should be noted that HPV positive status has a favorable prognostic value only for oropharyngeal primary cancers and not for other cancers of the head and neck.
With regards to anal carcinoma, there appears to be a relationship between cervical, anogenital and oropharyngeal cancer suggesting a genital-anal-oral transmission of HPV. Patients with HIV infection have a higher risk of developing HPV associated anal carcinoma and antiretroviral therapy does not decrease this risk. Anal Pap test is recommended annually for high risk patients including those with a history of anogental warts and women with abnormal cervical or vulvar cytology. For patients with anal carcinoma, positive HPV status does not confer a favorable prognosis as is the case for patients with oropharygeal carcinoma. GARDASIL®, a quadrivalent vaccine targeting HPV-6,11,16 and 18 as well as CERVARIX®, a bivalent vaccine targeting HPV-16 and 18 are presently available in the U.S. They are recommended for both females and males at an age as early as 9 years and given as a 3 shot series, to prevent HPV related Cervical Intraepithelial lesions/cervical cancer and genital warts/Anal Intraepithelial Neoplasia respectively. The authors conclude that HPV infection and associated malignancies are preventable and attempts should be made to eradicate this virus. Zandberg DP, Bhargava R, Badin S, et al. CA Cancer J Clin 2013;63:57-81
Impact of More Restrictive Blood Transfusion Strategies on Clinical Outcomes A Meta-analysis and Systematic Review
SUMMARY: The traditional hemoglobin trigger to recommend blood transfusions for majority of the Health Care Providers is between 7.5 and 9 g/dl. The clinical rationale is based on the premise that increasing Hgb levels increases blood oxygen content and possible oxygen delivery to the tissues. However, there are no randomized trials validating improved oxygen delivery to tissues or better clinical outcomes in any setting at this hemoglobin transfusion trigger. The authors in this provocative study conducted a comprehensive research and performed a Primary and Secondary meta-analysis. In their primary meta-analysis, they reviewed the pooled data from 3 randomized clinical trials with 2364 patients and in these trials, a less than 7g/dl hemoglobin as a transfusion trigger (restrictive transfusion strategy) was compared with a more liberal transfusion strategy and outcomes were evaluated. These endpoints included mortality, acute coronary syndrome, pulmonary edema, infections and re-bleeding risk. The combined data from these 3 trials showed that a restrictive transfusion strategy resulted in a 26% mortality reduction in hospitalized patients, 20% reduction in total mortality, 36% reduction in the risk of re-bleeding, 56% reduction in acute coronary syndrome, 52% reduction in the incidence of pulmonary edema and 14% reduction in bacterial infections, compared with a more liberal transfusion strategy. The secondary meta-analysis evaluated patients in 16 trials (these were excluded from the primary meta-analysis) that used a less restrictive transfusion trigger (hemoglobin transfusion triggers of 7.5-10g/dl) and the authors noted that outcomes were not improved with a more liberal transfusion strategy. Further it was also noted that several observational studies have shown that Hgb levels of 5-6g/dl was well tolerated in normovolemic patients without effecting oxygen delivery. Contrary to clinical presumptions, these counter-intuitive findings can be explained based on sound physiologic principles. Normovolemic hemodilution following administration of crystalloid or colloid solutions, to replace blood loss, has been associated with a reduction in systemic vascular resistance, increase in cardiac output, coronary and cerebral blood flow and synthesis of 2,3-diphosphoglycerate in red blood cells thus maintaining movement of oxygen from red blood cells to body tissues. Liberal blood transfusions may in fact impair oxygen uptake by vital tissues by increasing the blood viscosity and the resulting loss of RBC function during preservation and storage of blood. Studies have also shown that in patients with gastrointestinal bleeding, restrictive transfusion strategy results in a lower portal blood pressure and less recurrent bleeding, as higher blood pressures might disrupt a thrombus plug. The authors following this clinically relevant meta-analysis concluded that restrictive transfusion strategy resulted in better outcomes and transfusion triggers should be evidence based. Salpeter SR, Buckley JS and Chatterjee S. The American Journal of Medicine 2014;127:124-131
Clinical Cancer Advances 2013 Annual Report on Progress Against Cancer From the American Society of Clinical Oncology
SUMMARY: Immune checkpoints are cell surface inhibitory proteins/receptors that harness the immune system and prevent uncontrolled immune reactions. Immune checkpoints are an area of increasing interest as they utilize the patient’s immune system to reject cancer cells. Survival of cancer cells in the human body may be to a significant extent, related to their ability to escape immune surveillance, by inhibiting T lymphocyte Activation .
The T cells of the immune system play a very important role in modulating the immune system. EFFECTOR T cells include Cytotoxic T cells, Helper T cells, and Natural Killer (NK) cells, that enable the immune system to destroy cancer cells and pathogens. The REGULATORY T cells however, suppress immune response. Under normal circumstances, inhibition of an intense immune response and switching off the EFFECTOR T cells of the immune system, is an evolutionary mechanism and is accomplished by Immune checkpoints or gate keepers. The mechanism can be compared to a lock and key where the appropriate Ligand (KEY) binds to the Immune checkpoint protein/receptor (LOCK) and activates or inhibits a T lymphocyte. With the ongoing understanding of tumor immunology and the recognition of Immune checkpoint proteins, researchers have focused on the development of antibodies that either target the membrane bound inhibitory Immune checkpoint proteins/receptors such as CTLA-4, PD-1, IDO, etc. (LOCK) or target the inhibitory soluble Ligands or antigens that are located on the surface of certain cancer cells (KEY) that bind to these Immune check point proteins/receptors. By doing so, one would expect to unleash the EFFECTOR T cells resulting in T cell proliferation, activation and a therapeutic response. The first immune checkpoint protein to be clinically targeted was CTLA-4. YERVOY® (Ipilimumab), an antibody that blocks Immune checkpoint protein/receptor CTLA-4, was approved by the FDA in March 2011 and has been shown to prolong overall survival in patients with previously treated unresectable or metastatic melanoma. The next immune check point protein/receptor studied for targeted therapy was PD-1. Lambrolizumab (MK-3475) is a humanized anti–PD-1 monoclonal antibody that demonstrated a 38% rapid and durable response rate and a more than 7 month median progression-free survival in patients with advanced melanoma, regardless of their prior therapy with YERVOY®. Nivolumab, another PD-1 targeted antibody demonstrated remarkable efficacy in a Phase I study with an overall response rate of 30%, median survival of 16.8 months and a 2 year survival of 44%. Based on this provocative data, a combination of Nivolumab and YERVOY® were studied in patients with advanced Stage III or IV melanoma who had received up to three prior therapies.. The idea was to block both the Immune checkpoints, PD-1 and CTLA-4, for improved efficacy. Fifty three (N=53) patients were treated with a combination of these two agents and 33 patients received these agents sequentially. Indeed, the highest response rate was over 50% in the combination group with 30% of these patients experienced a more than 80% response rate at 12 weeks of treatment whereas the response rate in the sequential treatment group was 20%. This preliminary study confirmed that blocking multiple Immune checkpoint proteins/receptors may result in rapid and durable responses in patients with advanced malignant melanoma. Phase III studies are underway to confirm this efficacy data and this concept is also being studied in other tumor types. Targeting/inhibiting the ligands (KEY) and preventing their binding to the Immune checkpoint protein/receptor, is another approach to stimulate antitumor immune response. PD-L1 protein (Ligand) which is often elevated in melanoma tumor cells, bind to PD-1 check point protein/receptor and can inhibit T cells and escape immune surveillance. An investigational PD-L1 targeted (Ligand targeted) engineered antibody (MPDL3280A) demonstrated a rapid response in 26% of the 45 patients with metastatic melanoma and the benefit was more so in those tumors expressing PD-L1. Promising activity has also been seen in advanced renal cell carcinoma. Antibodies targeting the Immune checkpoint receptor/protein or the Ligands binding to these receptors, are being developed, to carry payloads that are lethal to the checkpoint protein/receptor or Ligand. In conclusion, identifying as well as inhibiting certain Immune checkpoint proteins/receptors and/or Ligands that bind to these receptors, may give us new insights in the field of tumor immunology, resulting in better outcome for our cancer patients. Patel JD, Krilov L, Adams S, et al. J Clin Oncol 2013;32:129-160
American Society of Clinical Oncology 2013 Top Five List in Oncology
SUMMARY: The 2013 Top five list in Oncology was published to optimize the use of diagnostic and therapeutic modalities and enhance patient care, by following evidence-based guidelines, thereby providing cost-effective medical care.
1) Do not give patients starting a chemotherapy regimen that has a low or moderate risk of causing nausea or vomiting antiemetic drugs intended for use with a regimen that has a high risk of causing nausea or vomiting.
Highly emetogenic chemotherapy: The recommendations are a three drug combination of an NK1 receptor antagonist given on days 1-3 for oral Aprepitant (EMEND®) or IV EMEND® given on Day 1 only, a 5-HT3 receptor antagonist given on day 1 only and Dexamethasone (DECADRON®) given on days 1-3 or 4.
Moderately emetogenic chemotherapy: A two drug combination of Palonosetron (ALOXI®) given on day 1 only and DECADRON® given on days 1-3 is recommended. Even though ALOXI® is the preferred agent, a first-generation 5-HT3 serotonin receptor antagonist such as Granisetron (KYTRIL®) or Ondansetron (ZOFRAN®) may be substituted if it is not feasible to give ALOXI®.
Low emetogenic chemotherapy: A 5-HT3 serotonin receptor antagonist is recommended. Patients experiencing nausea and vomiting while on Radiation therapy may need prophylaxis with these agents throughout the course of their therapy.
2) Do not use combination chemotherapy (multiple drugs) instead of chemotherapy with one drug when treating an individual for metastatic breast cancer unless the patient needs a rapid response to relieve tumor-related symptoms.
Combination chemotherapy for metastatic Breast Cancer is only recommended when a patient has significant symptoms related to tumor burden and a rapid tumor response is needed for symptom palliation. Because combination chemotherapy can be associated with significant toxicity without improvement in overall survival (OS), it is recommended that single agent therapy given sequentially reduces the risk of toxicity besides allowing optimal drug delivery and could improve quality of life, without compromising OS. It should be noted however that in tumors overexpressing a specific biomarker such as HER 2, anti–HER 2 therapy in combination with cytotoxic chemotherapy can improve survival compared with chemotherapy alone. Patients with hormone receptor–positive tumors should receive sequential endocrine therapies before cytotoxic chemotherapy, in the absence of life threatening organ dysfunction. Combining cytotoxic chemotherapy with an anti-hormonal agent is not beneficial. Rapid symptom palliation using Radiation treatment, insertion of a stent, surgical intervention, etc., if more efficacious, has to be considered under appropriate circumstances, before initiating chemotherapy.
3) Avoid using positron emission tomography or positron emission tomography–computed tomography scanning as part of routine follow-up care to monitor for cancer recurrence in asymptomatic patients who have finished initial treatment to eliminate the cancer unless there is high-level evidence that such imaging will change the outcome.
Once staging and restaging is complete, routine surveillance using PET or PET-CT scanning for solid tumors and lymphomas remains unproven and is not recommended. This has been validated in multiple studies and has been endorsed by cancer organizations both in the U.S. and abroad.
4) Do not perform prostate-specific antigen testing for prostate cancer screening in men with no symptoms of the disease when they are expected to live fewer than 10 years.
Elevated levels of PSA can be associated with conditions other than Prostate Cancer such as Benign Prostate Hyperplasia. Even though men who undergo PSA testing are less likely to die specifically as a result of prostate cancer, when all cause mortality is taken into consideration, men undergoing PSA screening do not live any longer than those who do not undergo screening. If the life expectancy of an individual is less than 10 years based on medical conditions, PSA screening is unlikely to benefit this individual, as there is a greater probability of dying as a result of the underlying medical problems rather than asymptomatic prostate cancer. The US Preventive Services Task Force, American College of Physicians, American Urological Association, have all changed their recommendations in accordance to these findings.
5) Do not use a targeted therapy intended for use against a specific genetic aberration unless a patient’s tumor cells have a specific biomarker that predicts an effective response to the targeted therapy.
Targeted therapy is expensive and can be associated with toxicities, but can benefit patients significantly if their tumor cells demonstrate the specific gene alteration that makes the tumor cells susceptible to the targeted therapy. Usually, a specific biomarker is present in the tumor cells that may in turn predict effectiveness of the targeted therapy. Exceptions include high level evidence supporting the use of a targeted agent despite absence of the biomarker. It is recommended that targeted agents be used only as intended.
Schnipper LE, Lyman GH, Blayney DW, et al. J Clin Oncol 2013;31:4362-4370
PROSE Randomized proteomic stratified phase III study of second line erlotinib versus chemotherapy in patients with inoperable non–small cell lung cancer (NSCLC)
SUMMARY: VeriStrat ® is a clinically validated serum/plasma-based assay, for patients with advanced Non Small Cell Lung Cancer (NSCLC). VeriStrat® is a serum test of prognostic and predictive value that classifies patients as VeriStrat-Good (VS-G) or VeriStrat-Poor (VS-P) based on eight mass spectral peaks or proteomic patterns of the patients serum. Proteomics is the large-scale study of protein structure and functions. VeriStrat® testing is protein based and therefore has no correlation with known genomic biomarkers. It is well established that EGFR-TKIs (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors) are more effective in NSCLC patients with EGFR activating mutations. PROSE is a multicenter, double blind, randomized, VeriStrat® stratified, phase III study. In this trial, over 90% of the patients had no EGFR mutations (EGFR-Wild Type). Two hundred and eighty five (285) patients with advanced NSCLC who had first line treatment regimen with platinum-based therapy were randomly assigned to receive second line chemotherapy (CT) with single agent ALIMTA® (Pemetrexed) or TAXOTERE® (Docetaxel), at standard doses (N=129) or TARCEVA® (Erlotinib) 150 mg po qd (N=134). Patients and study investigators were blinded to the patients VeriStrat® status. Patients were classified as VeriStrat-Good or VeriStrat-Poor based on the VeriStrat® results. Patients in the treatment groups were stratified by age, gender, tumor histology, ECOG-PS and smoking history. Crossover was permitted upon disease progression. The primary objective of the study was to demonstrate differential treatment benefit between TARCEVA® and CT with regards to Overall Survival (OS). Median overall survival (OS) was 9 months for the patients in the CT group and 7.7 months for TARCEVA® group and this was not statistically significant (P=0.3). However when evaluated by VeriStrat® status, CT was beneficial for the VeriStrat-Poor patients compared to TARCEVA®, with significantly better median OS (6.3 vs 3 months, P=0.02). Age, gender, histology (squamous vs non-squamous) and smoking history had no impact on the overall survival. The authors concluded that patients classified as VeriStrat-Poor have better survival with CT than TARCEVA®, whereas patients classified as VeriStrat-Good have similar survival with TARCEVA® and CT. VeriStrat® testing therefore, can help physicians choose between TARCEVA® and CT, for their patients with advanced NSCLC. This test helps physicians identify patients who are likely to have good or poor outcomes after treatment with EGFR inhibitors and thereby can provide valuable insight into whether CT or targeted therapy with TARCEVA®, a EGFR-TKI, is appropriate for their patients with advanced NSCLC, in the second line setting. This information is especially important for patients without an EGFR mutation or for those, whose EGFR mutation status is unknown. Sorlini C, Barni S, Petrelli F, et al. J Clin Oncol 29: 2011 (suppl; abstr TPS214)