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issn:1549-490
1.  Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future 
The Oncologist  2014;19(8):851-859.
This study discusses the evolution of adjuvant trials in renal cell carcinoma from the immunotherapy era to the targeted therapy era, addresses the pitfalls of current studies to provide a context for interpreting forthcoming results, and outlines avenues to incorporate promising investigational agents, such as PD-1 inhibitors and MET inhibitors, in future adjuvant trials.
At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials.
doi:10.1634/theoncologist.2014-0105
PMCID: PMC4122473  PMID: 24969163
Adjuvant; Renal cell carcinoma; ASSURE; SORCE; S-TRAC; PROTECT; EVEREST
2.  Biomarker Validation: Common Data Analysis Concerns 
The Oncologist  2014;19(8):886-891.
Statistical concerns such as confounding and multiplicity, for which solutions have existed for years, are common in biomarker validation studies; however, published validation studies may not address these issues. By not only raising the issues but also describing possible solutions, this discussion may help decrease false discovery and enhance the reproducibility of validation study findings.
Biomarker validation, like any other confirmatory process based on statistical methodology, must discern associations that occur by chance from those reflecting true biological relationships. Validity of a biomarker is established by authenticating its correlation with clinical outcome. Validated biomarkers can lead to targeted therapy, improve clinical diagnosis, and serve as useful prognostic and predictive factors of clinical outcome. Statistical concerns such as confounding and multiplicity are common in biomarker validation studies. This article discusses four major areas of concern in the biomarker validation process and some of the proposed solutions. Because present-day statistical packages enable the researcher to address these common concerns, the purpose of this discussion is to raise awareness of these statistical issues in the hope of improving the reproducibility of validation study findings.
doi:10.1634/theoncologist.2014-0061
PMCID: PMC4122484  PMID: 25001264
Biomarker; Selection bias; Confounding factors; Validation studies
3.  Management of Advanced Prostate Cancer in Senior Adults: The New Landscape 
The Oncologist  2015;20(2):230.
doi:10.1634/theoncologist.2012-S1-16erratum
PMCID: PMC4319621  PMID: 25660834
4.  Cardiopulmonary Exercise Testing in Cancer Patients: Should We Really Refrain From Considering It for Preparticipation Screening? 
The Oncologist  2015;20(2):228.
Cardiopulmonary exercise testing (CPET) should continue to be taken into consideration when screening cancer patients for participation in exercise training programs. The benefits of CPET for cancer patients are better examined through longitudinal rather than cross-sectional studies.
doi:10.1634/theoncologist.2014-0366
PMCID: PMC4319636  PMID: 25660832
5.  In Reply 
The Oncologist  2015;20(2):228.
The primary goal is to ensure that exercise training is safe for all cancer patients without creating unnecessary barriers to exercise participation. On the basis of the study findings, the conclusion that exercise testing does not need to be an aspect of pre-exercise clearance for the majority of cancer patients remains appropriate. Nevertheless, these findings are preliminary, and it is hoped that they will stimulate further work.
doi:10.1634/theoncologist.2014-0376
PMCID: PMC4319637  PMID: 25660833
6.  The European Medicines Agency Approval of Axitinib (Inlyta) for the Treatment of Advanced Renal Cell Carcinoma After Failure of Prior Treatment With Sunitinib or a Cytokine: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use 
The Oncologist  2015;20(2):196-201.
Based on a positive opinion from the European Medicines Agency, a marketing authorization valid throughout the European Union (EU) was issued for axitinib (Inlyta) for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine. This paper summarizes the scientific review of the application leading to approval in the EU.
Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Based on the positive opinion from the European Medicines Agency (EMA), a marketing authorization valid throughout the European Union (EU) was issued for the treatment of advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine. The demonstration of clinical benefit for axitinib was based on a phase III, randomized, open-label, multicenter study of axitinib compared with sorafenib in patients with advanced RCC after failure of a prior systemic first-line regimen containing one or more of the following agents: sunitinib, bevacizumab plus interferon-α, temsirolimus, or cytokines. In the primary analysis, a 2-month increase in median progression-free survival (PFS) was observed for axitinib compared with sorafenib (hazard ratio [HR]: 0.665; 95% confidence interval [CI]: 0.544–0.812; p < .0001). In the subgroup of patients with a prior cytokine-containing regimen, the increase in median PFS associated with axitinib was 5.4 months (updated analysis, HR: 0.519; 95% CI: 0.375–0.720; p < .0001). In the subgroup of patients with prior sunitinib treatment, the increase in median PFS was 1.4 months (updated analysis, HR: 0.736; 95% CI: 0.578–0.937; p = .0063). The analysis of overall survival showed no statistically significant survival benefit of axitinib over sorafenib in patients previously treated with cytokine-containing regimens (HR: 0.813; 95% CI: 0.556–1.191) or sunitinib (HR: 0.997; 95% CI: 0.782–1.270). The most common treatment-related adverse events associated with axitinib included diarrhea, hypertension, fatigue, nausea, decreased appetite, dysphonia, and palmar-plantar erythrodysesthesia. Most of these events were mild or moderate in severity. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
doi:10.1634/theoncologist.2014-0177
PMCID: PMC4319625  PMID: 25616431
Axitinib; Inlyta; Renal cell carcinoma; EMA; European Medicines Agency
7.  A Randomized Phase II Study of Carboplatin With Weekly or Every-3-Week Nanoparticle Albumin-Bound Paclitaxel (Abraxane) in Patients With Extensive-Stage Small Cell Lung Cancer 
The Oncologist  2015;20(2):105-106.
Background.
Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules.
Methods.
This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m2 on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles.
Results.
Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual.
Conclusion.
Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments.
doi:10.1634/theoncologist.2014-0327
PMCID: PMC4319632  PMID: 25616430
8.  Dose-Dense Nonpegylated Liposomal Doxorubicin and Docetaxel Combination in Breast Cancer: Dose-Finding Study 
The Oncologist  2015;20(2):109-110.
Background.
Anthracyclines and taxanes are effective drugs in breast cancer (BC), but their toxicity profiles limit their use in combination. A dose-finding study was performed to determine maximum tolerated doses (MTDs) of nonpegylated liposomal doxorubicin (TLC-D99) and docetaxel (DTX) as a dose-dense schedule, to maintain dose intensity, and to limit toxicity, particularly cardiac.
Methods.
Twenty-four patients were enrolled, 12 with metastatic BC, 5 with locally advanced BC, and 7 with early BC. An intra- and interpatient approach was planned in two sequential steps. In the first step, TLC-D99 was administered at dose levels of 40, 45, and 50 mg/m2 plus DTX at a fixed dose of 50 mg/m2. In the second step, TLC-D99 was administered at the dose established in the first step plus DTX at dose levels of 55, 60, and 65 mg/m2. Every treatment cycle was delivered on day 1 every 14 days. Pegylated granulocyte colony-stimulating factor was scheduled on day 2. Dose-limiting toxicities (DLTs) were defined as G4 hematological; G3 nonhematological; ≥10% or ≥20% left ventricular ejection fraction (LVEF) reduction if the final value was <50% or ≥50%, respectively; severe arrhythmia; and symptomatic heart failure. LVEF was evaluated by echocardiography every two cycles, and precursor brain natriuretic peptide (pBNP) and cardiac troponin I (cTnI) were monitored on days 1 and 2.
Results.
Five DLTs occurred (20.8%). No cardiac event of congestive heart failure was reported; 2 events of grade 3 cardiac dysfunction (8.3%), including a ≥20% LVEF reduction in 1 patient and symptomatic arrhythmia in another; 2 incidences of G4 neutropenia (8.3%); and 1 occurrence of G3 asthenia (4.2%) were reported. MTDs were not reached. The recommended doses were established as TLC-D99 50 mg/m2 and DTX 65 mg/m2. Cumulatively, mild (G1–G2) cardiac dysfunction was observed in 58.4% of patients: G1 cardiac arrhythmia was noted in 50%, G1–G2 general cardiac toxicity occurred in 25%, and concomitant toxicity was present in 17%. cTnI never increased. pBNP was increased in 25% and was associated with limiting arrhythmia in 4% and cardiac dysfunction in 16%.
Conclusion.
Dose-dense TLC-D99 50 mg/m2 and DTX 65 mg/m2 can be safely administered in combination every 2 weeks for breast cancer, with the highest projected dose intensity for each drug at 25 and 32.5 mg/m2 per week, respectively.
doi:10.1634/theoncologist.2014-0129
PMCID: PMC4319623  PMID: 25601964
9.  Breaking Down the Evidence for Bevacizumab in Ovarian Cancer 
The Oncologist  2015;20(2):91-93.
Bevacizumab has been FDA-approved for use in combination with single-agent chemotherapy for platinum-resistant ovarian cancer; however, its optimal role remains unclear. In this editorial, the timing, efficacy, safety, and rationale for use of bevacizumab in ovarian cancer are discussed.
doi:10.1634/theoncologist.2014-0302
PMCID: PMC4319628  PMID: 25601962
10.  Standard Versus Continuous Administration of Capecitabine in Metastatic Breast Cancer (GEICAM/2009-05): A Randomized, Noninferiority Phase II Trial With a Pharmacogenetic Analysis 
The Oncologist  2015;20(2):111-112.
Background.
The approved capecitabine regimen as monotherapy in metastatic breast cancer (MBC) is 1,250 mg/m2 twice daily for 2 weeks on and 1 week off (Cint). Dose modifications are often required because of severe hand-foot syndrome (HFS). We tested a continuous regimen with a lower daily dose but a similar cumulative dose in an attempt to reduce the severity of adverse events (AEs) while maintaining efficacy.
Methods.
We randomized 195 patients with HER-2/neu-negative MBC to capecitabine 800 mg/m2 twice daily throughout the 21-day cycle (Ccont) or to Cint to assess noninferiority in the percentage of patients free of progression at 1 year. Secondary endpoints included efficacy and safety. Associations between polymorphisms in capecitabine metabolism-related genes and drug response were assessed.
Results.
The percentage of patients free of progression at 1 year was 27.3% with Cint versus 25.3% with Ccont (difference of −2.0%; 95% confidence interval: −15.5% to 11.5%, exceeding the 15% deemed noninferior). Differences regarding other efficacy variables were also not found. Grade 3–4 HFS was the most frequent AE (41.1% in Cint vs. 42.3% in Ccont). Grade 3–4 neutropenia, thrombocytopenia, diarrhea, and stomatitis were more frequent with Cint. A 5′ untranslated region polymorphism in the carboxylesterase 2 gene was associated with HFS. One polymorphism in cytidine deaminase and two in thymidine phosphorylase were associated with survival.
Conclusion.
Our study was unable to show noninferiority with the continuous capecitabine regimen (Ccont) compared with the approved intermittent regimen (Cint). Further investigation is required to improve HFS. Polymorphisms in several genes might contribute to interindividual differences in response to capecitabine.
doi:10.1634/theoncologist.2014-0379
PMCID: PMC4319639  PMID: 25601966
11.  Bevacizumab in Combination With Radiotherapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma Multiforme 
The Oncologist  2015;20(2):107-108.
Background.
Patients with a newly diagnosed glioblastoma multiforme (GBM) have a high risk of recurrent disease with a dismal outcome despite intensive treatment of sequential surgery and chemoradiotherapy with temozolomide (TMZ), followed by TMZ as a single agent. Bevacizumab (BV) may increase response rates to chemotherapy in the recurrent treatment setting of GBM. We hypothesized that a neoadjuvant treatment strategy for patients with newly diagnosed GBM using chemoradiotherapy plus BV would improve resectability and thus survival. We performed a phase II trial of the treatment strategy of BV plus chemoradiation to determine the safety of this combination in patients who had already undergone primary surgery for their GBM.
Methods.
After a biopsy (6 patients) or a resection (13 patients) of a newly diagnosed GBM, 19 patients received radiotherapy (30 fractions of 2 Gy) in combination with daily TMZ 75 mg/m2 and BV 10 mg/kg on days 1, 14, and 28, followed by 6 monthly cycles of TMZ 150–200 mg/m2 on days 1–5.
Results.
The overall response rate was 26%. Three patients had a complete response after resection, and in two patients, a complete response after resection followed by chemoradiation plus BV was seen. No grade 3–4 toxicities were observed during combination treatment. The median progression-free survival was 9.6 months (95% confidence interval [CI]: 4.3–14.4 months). The median overall survival was 16 months (95% CI: 8.1–26.3 months), similar to a matched control group that received standard chemoradiotherapy from our institution.
Conclusion.
Combination of bevacizumab with radiotherapy and TMZ is safe and feasible in patients with newly diagnosed GBM, but because of low response rates, this treatment strategy does not favor a neoadjuvant approach.
doi:10.1634/theoncologist.2014-0418
PMCID: PMC4319643  PMID: 25582142
12.  Breaking Bad News in Bolivia 
The Oncologist  2015;20(2):227.
A medical oncologist considers the authentic meaning of the word unessential with regard to the cost of care.
doi:10.1634/theoncologist.2014-0396
PMCID: PMC4319642  PMID: 25561509
13.  Active Smoking May Negatively Affect Response Rate, Progression-Free Survival, and Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib 
The Oncologist  2013;19(1):51-60.
An international multicenter retrospective study of sunitinib-treated metastatic renal cell carcinoma patients was performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. The results showed that active smoking may negatively affect the progression-free and overall survival of these patients.
Learning Objectives
Describe the association between risk factors for renal cell carcinoma and the outcome of sunitinib treatment for metastatic disease.Explain the impact of active smoking on the outcome of sunitinib-treated metastatic renal cell carcinoma.Discuss obesity, hypertension, and diabetes in relation to the outcome of sunitinib-treated metastatic renal cell carcinoma.
Background.
Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC).
Methods.
An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors.
Results.
Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002).
Conclusion.
Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.
doi:10.1634/theoncologist.2012-0335
PMCID: PMC3903056  PMID: 24309979
Active smoking; Metastatic renal cell carcinoma; Outcome; Sunitinib treatment
14.  New Oral Anticoagulants and the Cancer Patient 
The Oncologist  2013;19(1):82-93.
New oral anticoagulants are now available that offer increased options for anticoagulation beyond the traditional vitamin K antagonists. In this report, the basic pharmacology, current clinical indications, and approach to the use of new oral anticoagulants in the cancer patient have been reviewed.
Learning Objectives
Cite the current indications, basic clinical pharmacology, and rationale for development of the new oral anticoagulants.Explain the potential risk for drug-drug interactions between the new oral anticoagulants and drugs commonly used in cancer patients.
Indications for anticoagulation are common in patients with malignancy. Cancer patients have an increased risk of developing venous thromboembolic events or may have other indications for anticoagulation, such as atrial fibrillation. New oral anticoagulants (NOACs) are now available that offer increased options for anticoagulation beyond the traditional vitamin K antagonists and low molecular weight heparins that have long been the cornerstone of treatment. This review will focus on the three NOACs that are currently approved for use in the U.S.: the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors, apixaban and rivaroxaban. Oncologists are likely to encounter an increasing number of patients taking these agents at the time of their cancer diagnosis or to have patients who develop indications for anticoagulation during the course of their disease. The basic pharmacology, current clinical indications, and approach to the use of NOACs in the cancer patient will be reviewed.
doi:10.1634/theoncologist.2013-0239
PMCID: PMC3903061  PMID: 24319019
Anticoagulants; Direct thrombin inhibitors; Factor Xa inhibitors; Venous thromboembolism; Cancer
15.  Barriers and Challenges to Global Clinical Cancer Research 
The Oncologist  2013;19(1):61-67.
Using data from the American Society of Clinical Oncology International Affairs Committee’s Web survey of selected oncologists with research experience from 25 countries, the authors explored the characteristics of and barriers to global clinical cancer research. They concluded that lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.
Background.
There are concerns about growing barriers to cancer research. We explored the characteristics of and barriers to global clinical cancer research.
Methods.
The American Society of Clinical Oncology International Affairs Committee invited 300 selected oncologists with research experience from 25 countries to complete a Web-based survey. Fisher’s exact test was used to compare answers between participants from high-income countries (HICs) and low- and middle-income countries (LMICs). Barriers to clinical cancer research were ranked from 1 (most important) to 8 (least important). Mann-Whitney’s nonparametric test was used to compare the ranks describing the importance of investigated obstacles.
Results.
Eighty oncologists responded, 41 from HICs and 39 from LMICs. Most responders were medical oncologists (62%) at academic hospitals (90%). Researchers from HICs were more involved with academic and industry-driven research than were researchers from LMICs. Significantly higher proportions of those who considered their ability to conduct academic research and industry-driven research over the past 5 years more difficult were from HICs (73% vs. 27% and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a lack of funding was ranked the most important (score: 3.16) barrier, without significant differences observed between HICs and LMICs. Lack of time or competing priorities and procedures from competent authorities were the second most important barriers to conducting academic clinical research in HICs and LMICs, respectively.
Conclusion.
Lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.
doi:10.1634/theoncologist.2013-0290
PMCID: PMC3903063  PMID: 24323390
Cancer research; Global; Barrier
16.  Local and Regional Staging of Invasive Breast Cancer With Sonography: 25 Years of Practice at MD Anderson Cancer Center 
The Oncologist  2013;19(1):5-15.
It has been observed that sonography is rarely used by many institutions in the local or regional staging of breast cancer. Findings suggest, however, that sonography has shown sufficient accuracy in clinical practice to stage most invasive breast cancers.
Learning Objectives
Outline the uses of sonography in staging local and regional breast cancer.Describe advantages of using sonography in staging local and regional breast cancer.
At The University of Texas MD Anderson Cancer Center, we have used sonography (US) extensively for more than 2 decades to refine the local and regional staging of invasive breast cancer. Although magnetic resonance imaging is superior to all other imaging modalities in the measurement of the primary tumor and detection of additional foci of malignancy, in our experience US has shown sufficient accuracy in clinical practice to stage most invasive breast cancers. The exceptions are ill-defined tumors such as invasive lobular cancers and tumors in breasts containing extensive diffuse benign disease. An advantage of US is that multifocality or multicentricity can be confirmed via US-guided fine-needle aspiration within 15 minutes and the information shared immediately with the patient and the breast surgeon or medical oncologist. US has also proved indispensable in the evaluation of lymphatic spread because it can evaluate more nodal basins (e.g., the supraclavicular fossa and low neck) than magnetic resonance imaging can and because it can guide needle biopsy to confirm the status of any indeterminate node (including internal mammary nodes) within minutes.
doi:10.1634/theoncologist.2013-0323
PMCID: PMC3903064  PMID: 24309983
Breast cancer; Ultrasonography; Local and regional staging; Lymph node metastases; Ultrasound-guided needle biopsy
17.  On Being a Doll 
The Oncologist  2013;19(1):100-101.
doi:10.1634/theoncologist.2013-0349
PMCID: PMC3903065  PMID: 24304713
Fiction; Cancer; Palliative care; End of life; Oncology
18.  Zollinger-Ellison Syndrome: Classical Considerations and Current Controversies 
The Oncologist  2013;19(1):44-50.
Surgery plays a key role in the management of Zollinger-Ellison syndrome; however, extent of resection, timing of intervention, performance of prophylactic adjunctive procedures, and reoperation for recurrent disease are topics of controversy. Historical considerations as well as evidence-based recommendations are summarized in this review.
Learning Objectives
Compare the approaches to management of sporadic and MEN-1 associated Zollinger-Ellison syndrome variants.Discuss the controversies in surgical and medical management of Zollinger-Ellison syndrome.
Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin-secreting tumors, responsible for causing the formation of multiple, refractory, and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main variants have been described, sporadic and those found in association with parathyroid and pituitary tumors, a genetic disorder known as multiple endocrine neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed by radiological or nuclear localization of the primary lesion, is mandated for establishing diagnosis. The mainstays of treatment include management of hypersecretory state with medical suppression of gastric acid production and surgical resection of primary tumor for the prevention of malignant transformation and metastatic complications. Medical therapy with proton pump inhibitors has virtually eliminated the need for acid-reducing surgical procedures. Surgical approach to sporadic and MEN-1-associated ZES varies based on our understanding of the natural history of the condition and the probability of cure; however, resection to a negative microscopic margin is indicated in both cases. Postoperative surveillance involves measurement of gastrin level, followed by imaging if elevation is detected. Re-excision of recurrent or resection of metastatic disease is a subject of controversy; however, at the present time aggressive cytoreductive approach is favored.
doi:10.1634/theoncologist.2013-0369
PMCID: PMC3903066  PMID: 24319020
Gastrinoma; Peptic ulcer; Multiple endocrine neoplasia type 1; Gastric acid
19.  U.S. Food and Drug Administration Approval Summary: Omacetaxine Mepesuccinate as Treatment for Chronic Myeloid Leukemia 
The Oncologist  2013;19(1):94-99.
The authors report relevant clinical information regarding the U.S. Food and Drug Administration approval of a new drug, omacetaxine mepesuccinate (Synribo), for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Omacetaxine mepesuccinate has shown activity and a favorable benefit to risk profile for the studied population. Further evidence of response durability to verify clinical benefit is pending.
On October 26, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval to omacetaxine mepesuccinate (Synribo; Teva Pharmaceuticals USA, Inc., North Wales, PA, http://www.tevausa.com) for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). The approval was based on the FDA review of data from 111 patients with CML in CP or in AP who had received two or more prior TKIs, including imatinib. Major cytogenetic response was achieved in 18% of patients with CP, with a median response duration of 12.5 months. Major hematologic response was achieved in 14% of patients with AP, with a median response duration of 4.7 months. The FDA safety evaluation was based on submitted data from 163 patients with CP or AP CML who had received at least one dose of omacetaxine mepesuccinate. The safety evaluation was limited by the single-arm design of the clinical trials as conducted in a small number of previously treated patients. The most common (≥20%) adverse reactions of any grade in enrolled patients included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, and infection. The FDA concluded that omacetaxine mepesuccinate has shown activity and a favorable benefit-to-risk profile for the studied population of adult patients with CML (CP or AP) with resistance and/or intolerance to two or more TKIs. Further evidence of response durability to verify clinical benefit is pending.
doi:10.1634/theoncologist.2013-0077
PMCID: PMC3903068  PMID: 24309980
FDA; Omacetaxine mepesuccinate; CML; Chronic myeloid leukemia
20.  Reducing Lung Cancer and Other Tobacco-Related Cancers in Europe: Smoking Cessation Is the Key 
The Oncologist  2013;19(1):16-20.
Tobacco use is the biggest preventable cause of cancer in the world, and nearly one-third of the burden of tobacco-related diseases occurs in Europe. Oncologists can support and participate in tobacco control research, help promote robust tobacco cessation policies in Europe, and guide smokers with cancer to effective treatment programs to help them quit.
doi:10.1634/theoncologist.2013-0085
PMCID: PMC3903069  PMID: 24319017
21.  Reflections 
The Oncologist  2014;19(1):3140-3141.
doi:10.1634/theoncologist.2014-1001
PMCID: PMC3903070
22.  U.S. Food and Drug Administration Approval Summary: Erlotinib for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations 
The Oncologist  2014;19(7):774-779.
Erlotinib was approved for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. The approval was based on demonstration of clinically important improvements in progression-free survival and objective response rate and an acceptable toxicity profile in a multicenter, open label trial comparing erlotinib with platinum-based doublet chemotherapy.
On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (≥30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (≥5%) grade 3 and 4 adverse reactions were rash and diarrhea.
doi:10.1634/theoncologist.2014-0089
PMCID: PMC4077454  PMID: 24868098
Erlotinib; EGFR mutations; Lung cancer; FDA
23.  Adjuvant Therapy-Related Shortening of Survival (ATRESS): An Underrated Phenomenon 
The Oncologist  2015;20(1):88.
Shortening of survival after dissemination following adjuvant treatment is not understood well enough and is difficult to search for in public databases because of the lack of specific search terms. We suggest using the acronym ATRESS, for “adjuvant therapy-related shortening of survival,” in future literature concerning this issue.
doi:10.1634/theoncologist.2014-0273
PMCID: PMC4294609  PMID: 25589500
24.  Two Decades of The Oncologist 
The Oncologist  2015;20(1):1-2.
The Editor-in-Chief reflects on the advances in oncology witnessed by the journal in its first two decades.
doi:10.1634/theoncologist.2014-0490
PMCID: PMC4294619  PMID: 25589499
25.  John Fitzpatrick: An Appreciation 
The Oncologist  2015;20(1):e1-e2.
doi:10.1634/theoncologist.2015-0005
PMCID: PMC4294620

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