The Oncologist recent issues

The Clinical Significance of Statistical Significance

Kane, R. C. — 2008-11-21

This review provides a clinical and non-Bayesian perspective on some key elements in the statistical design, analysis, and interpretation of randomized, comparative, phase III clinical trials intended to demonstrate superiority over a control treatment.

Commentary: Hormone Receptor Testing in Breast Cancer: A Distress Signal from Canada

Allred, D. C. — 2008-11-21

This commentary reviews recent events in Canada that underscore the substantial problems with estrogen receptor testing by immunohistochemistry in breast cancer.

Presurgical Systemic Treatment of Nonmetastatic Breast Cancer: Facts and Open Questions

2008-11-21

This paper provides an overview on the advantages and limits of the use of disease response after primary systemic therapy in clinical studies of nonmetastatic breast cancer.

False-Positive Serum Human Chorionic Gonadotropin (hCG) in a Male Patient with a Malignant Germ Cell Tumor of the Testis: A Case Report and Review of the Literature

Ballieux, B. E.P.B., Weijl, N. I., Gelderblom, H., van Pelt, J., Osanto, S. — 2008-11-21

Presented is a case report of the first male cancer patient to receive unneeded second- and third-line chemotherapy for a relapsed germ cell tumor based on false-positive serum human chorionic gonadotropin (hCG) results. The authors discuss the pitfalls of false-positive serum hCG measurements and review the literature.

Osteopontin Combined with CD44, a Novel Prognostic Biomarker for Patients with Hepatocellular Carcinoma Undergoing Curative Resection

2008-11-21

This study evaluates the prognostic significance of osteopontin and CD44 expression in hepatocellular carcinoma patients following curative resection. The authors find that osteopontin combined with CD44 is a promising independent predictor of tumor recurrence and survival.

Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC

Herbst, R. S., Sandler, A. — 2008-11-21

Because erlotinib and bevacizumab act on two different pathways critical to tumor growth and dissemination, administering these drugs concomitantly may confer additional clinical benefits to cancer patients with advanced disease, by virtue of their complementary antitumor activity. This article examines this combination as a viable second-line alternative to chemotherapy or erlotinib monotherapy in patients with non-small cell lung cancer.

Racism in the Chemotherapy Infusion Unit: A Nurse's Story

2008-11-21

This dialogue focuses on the experience of a racial minority chemotherapy infusion nurse when confronted with a racist patient.

Cancer Survivorship: A Pediatric Perspective

Landier, W., Bhatia, S. — 2008-11-21

This review describes some of the known late effects described in childhood cancer survivors in order to suggest reasonable starting points for evaluation of specific long-term problems in this unique and growing population.

Angiogenesis Inhibition in Non-GIST Soft Tissue Sarcomas

Sleijfer, S., van der Graaf, W. T.A., Blay, J.-Y. — 2008-11-21

This review discusses the currently available evidence supporting a role for angiogenic factors in the pathogenesis of soft tissue sarcoma and the first preliminary study results obtained with angiogenesis inhibitors.

Do Patients Die from Rashes from Epidermal Growth Factor Receptor Inhibitors? A Systematic Review to Help Counsel Patients About Holding Therapy

Jatoi, A., Nguyen, P. L. — 2008-11-21

The authors conducted a systematic review of the published, prospectively conducted clinical trial literature on epidermal growth factor receptor inhibitors to determine whether rash-related death has ever been reported. They found that there were no reported deaths from a typical rash and conclude that quality of life issues should remain at the forefront when making decisions about holding cancer therapy.

A Delicate Dance: Negotiating the Doctor-Patient Relationship During Cancer Treatment

Mariscotti, J. — 2008-11-21

The author reflects on the intricate dance of the patient–oncologist relationship experienced during her cancer journey.

Introduction

Weber, J. — 2008-11-10

The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation

Wolchok, J. D., Saenger, Y. — 2008-11-10

The survival rate of patients diagnosed with late-stage melanoma is poor—only 5%–10%. Enlisting the immune system in the fight against cancers such as melanoma could help improve the prognosis of these patients. Data have shown that melanocyte proteins make good targets for immune system–based therapy in this disease. However, self-tolerance, which develops to inhibit autoimmune attack, makes this strategy difficult. Two proteins on the surface of T cells—CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA-4)—play important roles in the regulation of immune activation and tolerance. CD28 provides positive modulatory signals in the early stages of an immune response, while CTLA-4 signaling inhibits T-cell activation, particularly during strong T-cell responses. CTLA-4 blockade using anti—CTLA-4 monoclonal antibody therapy has great appeal because suppression of inhibitory signals results in the generation of an antitumor T-cell response. Both clinical and preclinical data indicate that CTLA-4 blockade results in direct activation of CD4⁺ and CD8⁺ effector cells, and anti–CTLA-4 monoclonal antibody therapy has shown promise in a number of cancers, particularly melanoma. Interestingly, the occurrence of adverse events among patients treated with CTLA-4 blockade helps shed light on the mechanism of action of anti–CTLA-4 monoclonal antibodies. Most adverse events involve immune-related toxicity to the skin and gastrointestinal tract. Major gastrointestinal toxicity develops in up to 21% of treated patients, and while an objective response occurs in approximately 36% of melanoma patients who develop enterocolitis with treatment, an objective response is found in only 11% of patients who do not experience this adverse reaction.

Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Tremelimumab (CP-675,206)

Ribas, A. — 2008-11-10

Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade therapies have been evaluated in clinical trials and have shown promise as possible options for treating patients with cancer. One agent under investigation is tremelimumab (CP-675,206), a monoclonal antibody that has been demonstrated to be a safe and efficacious treatment in patients with malignant melanoma. Results of a phase I clinical trial suggested that a dose of 15 mg/kg of tremelimumab would be the maximum-tolerated dose, with the most common grade 3–4 toxicities being diarrhea and rash. Pharmacokinetic studies showed that the postinfusion plasma concentration and area under the plasma disposition curve both increased in an approximately proportional manner with dose. Studies also showed that tremelimumab has a low clearance (0.132 ml/h·kg), a small volume of distribution (81.2 ml/kg), and a long terminal-phase half-life (22.1 days). A pivotal phase II clinical trial assessing single-agent tremelimumab as second-line therapy in metastatic melanoma has completed accrual, with response rate as the primary endpoint. A pivotal phase III trial has also completed accrual; that study compared the overall survival of previously untreated patients receiving single-agent tremelimumab versus dacarbazine or temozolomide.

Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Ipilimumab (MDX-010)

Weber, J. — 2008-11-10

Targeted biologic therapies such as anti–cytotoxic T lymphocyte antigen (CTLA-4) monoclonal antibodies, either as monotherapy or in combination with chemotherapy or vaccines, have shown great promise in late-stage melanoma, which has a very poor prognosis. Melanoma is relatively resistant to both chemotherapy and radiotherapy. Blockade of CTLA-4, which inhibits T-cell proliferation, promotes stimulation of adaptive immunity and T-cell activation, resulting in eradication of tumor cells. Two human monoclonal antibodies are under investigation in melanoma. Phase II and III clinical trials are currently evaluating the efficacy and safety of ipilimumab (MDX-010, Medarex, Inc., Princeton, NJ, and Bristol-Myers Squibb, Princeton, NJ) and tremelimumab (CP-675,206; Pfizer Pharmaceuticals, New York) in melanoma. Data are available on ipilimumab, which has been explored as monotherapy and in combination with vaccines, other immunotherapies such as interleukin-2, and chemotherapies such as dacarbazine. Overall response rates range from 13% with ipilimumab plus vaccine in patients with stage IV disease to 17% and 22% with ipilimumab plus dacarbazine or interleukin-2, respectively, in patients with metastatic disease. Responses have been durable, and among those experiencing grade 3 or 4 autoimmune toxicities, even higher response rates have been seen—up to 36%. While the optimal dose of ipilimumab has yet to be established, studies also indicate that higher doses may be more effective. Importantly, the lack of an initial clinical response may not predict ultimate treatment failure, because the onset of a response may follow progressive disease or stable disease. Pending results from registration studies with ipilimumab and lessons learned from registration studies conducted with tremelimumab will help to define the role of anti–CTLA-4 blockade in the treatment of metastatic melanoma.

Dr. Joseph R. Bertino: A Reflection

Chabner, B. A. — 2008-10-23

This editorial honors Dr. Joseph R. Bertino on his award of the Pinedo Prize.

Transfer of Drug Resistance Genes into Hematopoietic Stem Cells for Marrow Protection

Bertino, J. R. — 2008-10-23

The study investigates the use of gene transfer with genes that confer drug resistance for the purpose of bone marrow protection from chemotherapy.

Commentary: Tumor Growth, Patient Survival, and the Search for the Optimal Phase II Efficacy Endpoint

Takimoto, C. H. — 2008-10-23

This commentary considers the Stein et al. manuscript published in this issue of The Oncologist.

Tumor Growth Rates Derived from Data for Patients in a Clinical Trial Correlate Strongly with Patient Survival: A Novel Strategy for Evaluation of Clinical Trial Data

2008-10-23

The study presents a new method to predict survival using tumor measurement data gathered while a patient with cancer is receiving therapy in a clinical trial. The method is described using prostate cancer as a model.

Bevacizumab Reduces the Growth Rate Constants of Renal Carcinomas: A Novel Algorithm Suggests Early Discontinuation of Bevacizumab Resulted in a Lack of Survival Advantage

Stein, W. D., Yang, J., Bates, S. E., Fojo, T. — 2008-10-23

The study uses data gathered while a patient is enrolled in a clinical trial to calculate a growth rate constant that provides an independent, unbiased assessment of treatment efficacy that may allow a rapid evaluation of drug activity.

Chemotherapy for Colorectal Cancer Liver Metastases

Alberts, S. R., Wagman, L. D. — 2008-10-23

The manuscript reviews treatment options for resectable and unresectable liver metastases from colorectal cancer. Advances in chemotherapy, regional treatment, imaging, and surgical techniques are radically changing the management of colorectal cancer liver metastases from palliative to survival prolonging.

Innovations in Chemotherapy for Metastatic Colorectal Cancer: An Update of Recent Clinical Trials

O'Neil, B. H., Goldberg, R. M. — 2008-10-23

Recent innovations in chemotherapy for metastatic colorectal cancer are reviewed, with a focus on emerging data that may significantly improve both survival and quality of life for patients with colorectal cancer in the future.

Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies

Hutson, T. E., Figlin, R. A., Kuhn, J. G., Motzer, R. J. — 2008-10-23

This paper describes the clinical rationale for the recommended dosing and reviews the safety data at clinical doses for each of the novel targeted therapies approved for the treatment of renal cell carcinoma: sunitinib, sorafenib, and temsirolimus.

Current and Emerging Strategies for the Management of Acute Myeloid Leukemia in the Elderly

Laubach, J., Rao, A. V. — 2008-10-23

This review highlights important host and disease characteristics of elderly acute myeloid leukemia patients and summarizes the current and emerging classes of drugs for the treatment of this disease.

Informed Consent Revisited: A Doctrine in the Service of Cancer Care

Schachter, M., Fins, J. J. — 2008-10-23

The authors propose a reinvigoration of the doctrine of informed consent in which the physician engages in meaningful and ongoing dialogue with the patient in order to avoid the unilateral burdens of paternalism and enhance the collaborative therapeutic enterprise.

FDA Drug Approval Summary: Lapatinib in Combination with Capecitabine for Previously Treated Metastatic Breast Cancer That Overexpresses HER-2

2008-10-23

This paper reports the results of the study that led to U.S. Food and Drug Administration approval of lapatanib in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress human epidermal growth factor receptor 2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

Lenalidomide in Combination with Dexamethasone for the Treatment of Multiple Myeloma After One Prior Therapy

2008-10-23

This report describes the key data and analyses for approval by the U.S. Food and Drug Administration of lenalidomide in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy.

Commentary: Practicing on the Tip of an Information Iceberg? Evidence of Underpublication of Registered Clinical Trials in Oncology

Ramsey, S., Scoggins, J. — 2008-10-23