ONCOLOGY Vol 20 No 14

The three papers contained in this supplement to ONCOLOGY were designed to serve as practical "keep on the shelf" references for the current management of metastatic colon cancer and screening and management of patients at high risk of colon cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in United States. For nearly 50 years, fluorouracil has been the only anticancer drug proven to benefit patients with metastatic CRC (mCRC), and it continues to be the backbone on which most treatment regimens are built. In the past 10 years, development of the topoisomerase I inhibitor irinotecan (Camptosar), the third-generation platinum analog oxaliplatin (Eloxatin), and the oral fluoropyrimidine capecitabine (Xeloda) advanced mCRC treatment and opened up an era of combination chemotherapy. More recently, monoclonal antibodies such as bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix) have become available for use in mCRC treatment in combination with cytotoxic agents and as monotherapies. The addition of these targeted agents to the mCRC treatment armamentarium has resulted in more therapeutic options and improved treatment outcomes for the patients. The prospect of mCRC treatment is ever promising as more targeted agents such as vatalanib are being introduced and as intelligent combination regimens are being designed based upon a better understanding of pharmacokinetics. In this article we review various treatment options, including cytotoxic and targeted agents, currently available for patients with mCRC.

Advances in molecular genetics have evolved at such a fast pace that physicians may be bewildered about their clinical translation into patient care. However, genetic counselors, particularly those trained in cancer genetics, have been extremely helpful. The challenge to the physician, however, calls for an understanding of the natural history of hereditary cancer syndromes, which is often reflected in the pedigree. Pedigree/family history information must be compiled in sufficient detail to arrive at the most likely hereditary cancer syndrome diagnosis so that the molecular geneticist can search for the mutation. Finally, the challenge to the clinician is melding this into an accurate diagnosis, in order to provide highly targeted screening and management for high-risk patients. This article is an attempt to crystallize all of these issues in a format that will help physicians—particularly those in the oncology community—to meet this challenge effectively.

Traditional therapeutic concepts and treatment regimens for colorectal cancer are currently changing with the demonstration of the efficacy of biologic agents in this disease setting. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to conventional chemotherapy in the first- and second-line settings has shown a survival benefit; this outcome has helped to rapidly change the standard of care. Other targeted agents, such as anti-epidermal growth factor receptor (EGFR) antibodies, have shown proof of efficacy in colorectal cancer as well. The molecular targeted therapies are associated with toxicity profiles that are distinctly different from those seen with conventional chemotherapy. A notable difference is the absence of high risk for myelosuppression, diarrhea, or alopecia, which are common side effects of cytotoxic chemotherapy. This article will explore the toxicities associated with targeted therapies in detail in an attempt to provide assistance to the practicing oncologist in detecting and managing these side effects in their patients. In particular, the article will focus on the side effects associated with the three currently approved targeted drugs: the anti-VEGF monoclonal antibody bevacizumab and the anti-EGFR monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix).

Metastatic hormone-resistant prostate cancer has proven largely resistant to cytotoxic therapy. Since 2004, docetaxel (Taxotere)/prednisone has become the standard chemotherapy used to treat advanced hormone-resistant prostate cancer. However, the survival advantage is modest and a significant number of patients do not respond to chemotherapy. It is hoped that an increased understanding of the mechanisms underlying the progression of prostate cancer will lead to new treatment modalities. With the growing number of biologic and targeted agents under development, the potential armamentarium of prostate cancer treatments is steadily growing. However, none of the new treatment modalities has yet been shown to be more effective than standard treatments. This article will provide an overview of targeted or innovative therapies in the treatment of prostate cancer.

Results from a Southwest Oncology Group (SWOG) study show that radiotherapy given to men with locally advanced prostate cancer after their prostate gland is removed does not significantly reduce the risk of subsequent cancer spread to distant sites but significantly lowers the risk of the cancer recurrence compared to men who do not receive radiation.

I was diagnosed with ovarian cancer seven and a half years ago. The news was overwhelming. The painting depicts how I began; absorbing the shock and then going through the feelings of loss, bewilderment, and fear of the unknown.

In their article, "Trastuzumab and Beyond: New Possibilities for the Treatment of HER2-Positive Breast Cancer," Drs. Morris and Carey provide an excellent summary of therapeutic progress in this disease, and also turn their attention to the challenge now facing us--that of understanding the heterogeneity of HER2-positive breast cancer and mechanisms of resistance to trastuzumab (Herceptin)-based therapy.

Bortezomib (Velcade) stops cancer growth in patients with advanced differentiated thyroid cancer who do not respond to the standard treatment of surgery and radioactive iodine, according to a recent study presented at the 77th Annual Meeting of the American Thyroid Association (ATA) in Phoenix.

The elegant and thoughtful review of current management of renal cell carcinoma, by Feldman and Motzer,[1] indicates that there has been clear and defined progress in the management of this frustrating disease. Our limited understanding of the biology of the immune response in renal carcinoma has led to the use of the interferons and varying doses of interleukin-2 (Proleukin), occasionally and inconsistently achieving spectacular, durable responses, but often at the cost of significant toxicity.

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis.

Roche announced that a large, international phase III study (NO16966) enrolling 2,035 previously untreated metastatic colorectal cancer patients met both of its primary endpoints.

Each year after the annual meeting of the American Society of Clinical Oncology (ASCO), the media is abuzz with reports on the latest cancer advances. The national nonprofit organization CancerCare has created a free guide for helping cancer patients understand how new findings might affect their treatment options.

Genentech, Inc, recently announced that it received a Complete Response Letter from the US Food and Drug Administration (FDA) for a supplemental Biologics License Application (sBLA) for bevacizumab (Avastin) with chemotherapy in first-line metastatic breast cancer.

This comprehensive guidebook is an invaluable reference for patients and health professionals as they navigate the murky waters of cancer treatment and survivorship. While several other books address only specific aspects of living with cancer and its aftermath, Silver's reference covers all aspects of life during and after cancer, touching on issues that range from pain management to responding to children's questions about cancer such as, "Are you going to die?"

Endocare, Inc, a medical device company focused on the development of minimally invasive technologies for tissue and tumor ablation, announced that six studies and papers demonstrating the effectiveness of cryoablation for treating renal cancer were published in a supplement to the July 2006 issue of Urology.

One of the best examples of the "bench to bedside" process is the development of trastuzumab (Herceptin) for HER2-overexpressed breast tumors. From the identification of the neu oncogene in 1984[1] and its subsequent cloning,[2] to the development of a humanized monoclonal antibody targeting HER2 that improved outcome not only in the metastatic setting[3] but also in the adjuvant setting[4-7] has been a long yet fruitful journey.

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis.

Will there be a shortage of oncologists in 2015? This is a question that needs to be answered now in order to design and promote programs and policies that can help assure that Americans have access to high-quality cancer care in the future. All signs point to a significant increase in cancer rates as the baby boomers reach 65 years of age and older.

Genentech, Inc, announced recently that the US Food and Drug Administration (FDA) approved trastuzumab (Herceptin), as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel, for the adjuvant treatment of HER2-positive node-positive breast cancer.

Metastatic hormone-resistant prostate cancer has proven largely resistant to cytotoxic therapy. Since 2004, docetaxel (Taxotere)/prednisone has become the standard chemotherapy used to treat advanced hormone-resistant prostate cancer. However, the survival advantage is modest and a significant number of patients do not respond to chemotherapy. It is hoped that an increased understanding of the mechanisms underlying the progression of prostate cancer will lead to new treatment modalities. With the growing number of biologic and targeted agents under development, the potential armamentarium of prostate cancer treatments is steadily growing. However, none of the new treatment modalities has yet been shown to be more effective than standard treatments. This article will provide an overview of targeted or innovative therapies in the treatment of prostate cancer.

Celebrating 20 years of providing practical reviews and peer commentaries to the oncology community in an effort to promote optimal cancer education and quality care for persons with cancer

This report describes the Food and Drug Administration's review of data and analyses leading to the approval of the oral iron chelator, deferasirox for the treatment of chronic iron overload due to transfusional hemosiderosis.

For the past 20 years, the systemic treatment of metastatic renal cell carcinoma (RCC) has been limited primarily to cytokines, with few patients showing benefit. However, recent advances in understanding the pathobiology of RCC have led to the identification of novel therapeutic targets for this disease. Drugs specifically designed to inhibit these targets have been developed, with several showing superior efficacy over traditional cytokine therapy. Moreover, these agents are well tolerated and have improved the span of progression-free, and in some cases, overall survival. As a result, between December 2005 and January 2006, two of these targeted therapies—sunitinib (Sutent) and sorafenib (Nexavar)—were approved by the US Food and Drug Administration for the treatment of advanced RCC. The authors review the clinical trials that have focused on these two drugs as well as those concentrating on two other promising agents, bevacizumab (Avastin) and temsirolimus. The ways in which these novel drugs are changing the standard of care for metastatic RCC and the future directions of RCC clinical trials are also discussed.

Up to 25% of patients diagnosed with breast cancer have tumors that overexpress HER2. HER2-positive breast cancer is highly proliferative, difficult to treat, and confers a poor prognosis. The advent of the anti-HER2 monoclonal antibody trastuzumab (Herceptin) has markedly altered the clinical course of both early and advanced HER2-driven breast cancer. Despite the use of trastuzumab, however, patients with HER2-positive breast cancer still experience disease progression. Overcoming that resistance to therapy is our next challenge. This review examines the current understanding of HER2 biology, the mechanisms of action of and resistance to trastuzumab, as well as new therapies on the horizon.

It has been more than 15 years since the initial approval of myeloid growth factors to reduce febrile neutropenia in cancer patients receiving myelosuppressive chemotherapy.[1] As with other novel therapeutics, the approval of filgrastim (Neupogen) did not mark the end of research in this area, but rather the beginning.