Ovarian Cancer

In the United States, approximately 180,000 women are diagnosed with breast cancer annually.

During this election year, approximately 1.4 million U.S. residents will be diagnosed with cancer. For U.S. presidential hopefuls Sen. Barack Obama and Sen. John McCain, cancer has hit close to home. Sen. McCain, 72, has been treated several times for squamous cell carcinoma and malignant melanoma. Sen. Obama lost his grandfather to prostate cancer and his mother to ovarian cancer.

The human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor with tyrosine kinase activity overexpressed in about 20% to 25% of invasive carcinomas of the breast.

The question of a well-defined role for the use of neoadjuvant chemotherapy in the treatment of ovarian cancer is recognized to be one of the most hotly debated issues in the management of female pelvic malignancies.[1-3] One group of oncologists would argue that it should be the rare patient (eg, with severe comorbidity) who is not a candidate for an initial attempt at maximal cytoreduction.[1]

Ovarian cancer is a unique malignancy. While the disease can spread hematogenously or via the lymphatic system, the bulk of the tumor is found on peritoneal surfaces. This peritoneal disease results from shedding of ovarian tumor cells into the peritoneal cavity, circulation of these cells throughout the abdomen and pelvis, and eventual implantation onto peritoneal surfaces.

Conventional therapy for advanced-stage ovarian cancer-ie, aggressive cytoreductive surgery followed by aggressive chemotherapy-was established more than 3 decades ago [Editor’s note: See Dr. Schwartz’s article, “Cytoreductive Surgery in the Management of Ovarian Cancer,” in last month’s issue of ONCOLOGY]. Since that time, no prospective randomized trials have been reported to confirm the efficacy of this treatment strategy.

The magnitude of the role surgical exploration and extirpation play in the contemporary management of patients with advanced ovarian cancer is hard to overstate. Beyond diagnostic confirmation, the aggressive posture taken to remove bulk disease provides-among other benefits-symptomatic relief, theoretically enhanced immunologic integrity, chemosensitivity, and improved survival characteristics.

As outlined in the comprehensive review by Dr. Schwartz, cytoreductive surgery followed by platinum-based chemotherapy is considered the standard of care in the initial management of patients with advanced ovarian cancer. Considering prognostic factors for patients with advanced disease, residual disease after primary surgery is still considered to be the most important modifiable prognostic factor influencing survival. This has again been recently confirmed by a large retrospective study including six different Gynecologic Oncology Group (GOG) studies.[1]

The standard management for advanced-stage ovarian cancer was established in the mid-1970s. At a 1974 National Cancer Institute Consensus Conference on Ovarian Cancer, Griffiths presented data supporting the role for aggressive cytoreductive surgery as the first step in the management of this disease, followed by cytotoxic chemotherapy.

Women’s reports of persistent, recent-onset symptoms linked to ovarian cancer-abdominal or pelvic pain, difficulty eating or feeling full quickly, and abdominal bloating-combined with CA125 testing may improve the early detection of ovarian cancer by 20%, according to Fred Hutchinson Cancer Research Center investigators (Cancer, published online June 23, 2008).

The population of the United States and other industrialized nations is aging rapidly. The increased life span allows for longer exposure to carcinogens and the accumulation of genetic alterations. Thus, the incidence of cancer is increasing along with the aging of the population.

SAN DIEGO-At the 2008 AACR annual meeting, investigators reported preliminary results with a number of novel compounds entering clinical trials.

Jay R. Harris, MD, will present the Gianni Bonadonna Breast Cancer Award lecture at the upcoming 2008 ASCO Breast Cancer Symposium being held September 5-7 in Washington DC. Dr. Harris is professor and chair of the Department of Radiation Oncology at the Dana-Farber Cancer Institute and the Brigham and Women’s Hospital at Harvard Medical School.

Epothilones, representing a newer class of naturally occurring antimicrotubule macrolides, have emerged as cytotoxic agents with significant antitumor activity against tumors that are resistant to taxanes.

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years.

A team of European investigators is taking a novel immunotherapeutic approach to advanced gastrointestinal tract tumors using the "trifunctional antibody" catumaxomab.

Photography exhibit features breast and ovarian cancer patients and families

FDA removes partial hold on Telcyta clinical development

Liposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

The increased approval of anticancer agents has led to unprecedented results, with improved quality of life and longer survival times, resulting in millions of individuals living with a diagnosis of cancer. Whereas these novel medical, surgical, and radiation regimens, or combinations thereof, are largely responsible for these remarkable achievements, a new, unexpected constellation of side effects has emerged. Most notably, cutaneous toxicities have gained considerable attention, due to their high frequency and visibility, the relative effectiveness of anti–skin toxicity interventions, and the otherwise decreasing incidence of systemic or hematopoietic adverse events. Optimal care dictates that dermatologic toxicities must be addressed in a timely and effective fashion, in order to minimize associated physical and psychosocial discomfort, and to ensure consistent antineoplastic therapy. Notwithstanding the critical importance of treatment-related toxicities, dermatologic conditions may also precede, coincide, or follow the diagnosis of cancer. This review provides a basis for the understanding of dermatologic events in the oncology setting, in order to promote attentive care to cutaneous health in cancer patients and survivors.

In a study published in the Journal of Women's Health (16:971-986, 2007), researchers from the Centers for Disease Control and Prevention and Thomson Healthcare found a distinct pattern of medical signs and symptoms that occurred prior to the detection of ovarian cancer.

This issue of ONCOLOGY Nurse Edition represents the full range of the cancer-management spectrum: Anna Schwartz and Laura Zitella, respectively, re-examine standard protocols and prevailing clinical assumptions in their review of evidence-based approaches toward relieving cancer-related fatigue and managing cancer patients' anemia. In contrast, Ellen Giarelli, in her cancer vaccine review, looks over the horizon at novel and promising approaches now under investigation for both treatment and prevention of cancer.

An acneiform-like skin toxicity is commonly observed in patients with solid tumors treated with epidermal growth factor receptor inhibitors (EGFRIs). This symptomatic rash is related to epidermal growth factor receptor (EGFR) inhibition in the skin. A positive relation between the presence and severity of treatment-related rash and survival has been consistently observed with all EGFRIs approved for clinical use. These findings suggest that rash may be a useful surrogate marker of successful EGFR inhibition and clinical benefit and therefore of possible use in identifying patients most likely to benefit from therapy, as well as to guide dose adjustments. Increasing drug dose until skin toxicity appears is being studied. Further studies are needed to thoroughly evaluate the value of skin toxicity as a surrogate marker for clinical benefit. Current treatments of the skin toxicity are empirical and oriented toward mitigating symptoms and not validated by well-controlled clinical trials. Rational treatments based on the biological mechanisms of the skin toxicity must be developed and tested in well-controlled clinical trials.

The patient, DB, is a 51-year-old white, married female with a strong family history of breast cancer. She presented for high-risk assessment and genetic testing following the discovery of a deleterious mutation in a family member.

The future of breast cancer therapies will involve agents targeting multiple aspects of the signaling pathway. At ASCO 2007, investigators reported encouraging preliminary activity for numerous agents in the pipeline.

Novel modulators of the polo-like kinase 1 (Plk1) pathway targeting the cell cycle may be effective as anticancer agents.

C.W., is a 46-year-old white female who presented to her gynecologist complaining of an egg-shaped mass between her right hip bone and umbilicus, and irregular menstrual cycles. Physical examination confirmed a large palpable mass in her lower abdominal area. Past medical history was unremarkable. She was not taking any regular medications. She has been married for 17 years and has worked as a respiratory therapist for 16 years in a large pediatric hospital. She had been actively participating in a program of daily exercise at an area health club that included aerobics and weight training. She is a social drinker and denies any illicit drug use.

Anastrozole (Arimidex): Conversion to regular approval for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. Issued September 2005.Bevacizumab (Avastin): Treatment of metastatic colon cancer. Issued June 2006. Bortezomib (Velcade): Treatment of previously treated mantle cell lymphoma. Issued December 2006. Capecitabine (Xeloda): Single-agent adjuvant treatment of Dukes’ stage C colon cancer in patients who have undergone complete resection of the primary tumor and for whom fluoropyrimidine therapy alone would be preferred. Issued June 2005. Cetuximab (Erbitux): For use in combination with radiation therapy for the treatment of patients with unresectable squamous cell cancer of the head and neck and for patients whose disease has metastasized despite use of standard chemotherapy. Issued March 2006. Dasatinib (Sprycel): Treatment of chronic myelogenous leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia. Issued June 2006. Decitabine (Dacogen): Treatment of myelodysplastic syndromes. Issued May 2006. Docetaxel (Taxotere): In combination with cisplatin and fluorouracil prior to radiotherapy for treatment of inoperable locally advanced squamous cell carcinoma of the head and neck. Issued October 2006. Erlotinib (Tarceva): Treatment of locally advanced or metastatic non–small-cell lung cancer following failure of at least one prior chemotherapy regimen. Issued November 2004; In combination with gemcitabine for first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer. Approved for this indication November 2005. Exemestane (Aromasin): Adjuvant treatment of postmenopausal women with estrogen receptor positive early breast cancer who have received 2 or 3 years of tamoxifen therapy and are switched to exemestane for completion of 5 years of adjuvant hormonal therapy. Issued October 2005.Gefitinib (Iressa): AstraZeneca and FDA approved new labeling for gefitinib limiting its use to cancer patients who are currently benefiting or have previously benefited from treatment with this agent. Distribution limited under a risk-management plan called Iressa Access Program. Issued June 2005.Gemcitabine (Gemzar): In combination with carboplatin for treatment of ovarian cancer. Issued July 2006.Lapatinib (Tykerb): Treatment in combination with capecitabine of advanced or metastatic breast cancer (HER2-positive). Issued March 2007.Lenalidomide (Revlimid): Treatment of patients with deletion 5q cytogenetic abnormality subtype of myelodysplastic syndrome. Issued December 2005. Treatment of multiple myeloma. June 2006.Letrozole (Femara): Adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. Issued January 2006.Nelarabine (Arranon): Accelerated approval for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Patients must have had failure of at least two prior chemotherapy regimens. Issued October 2005.Panitumumab (Vectibix): Treatment of colorectal cancer that has metastasized following standard chemotherapy. Issued September 2006. Pegaspargase (Oncaspar): Treatment of acute lymphoblastic leukemia in adults and children. Issued July 2006. Rituximab (Rituxan): First-line treatment of diffuse large B-cell, CD20 positive, non-Hodgkin’s lymphoma in combination with CHOP or other anthracycline-based chemotherapy regimens. Issued February 2006. Sorafenib (Nexavar): Treatment of advanced renal cell carcinoma in adults. Issued December 2005.Sunitinib maleate (Sutent): Treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Also accelerated approval for the treatment of advanced renal cell carcinoma based on partial response rates and response duration. Issued January 2006. Approved for first-line treatment of advanced renal cell carcinoma. Issued February 2007.Thalidomide (Thalomid): Treatment of multiple myeloma. Issued May 2006.Topotecan (Hycamtin): Treatment of cervical cancer. Issued June 2006.Trastuzumab (Herceptin): Expanded use of trastuzumab post surgery in combination with other cancer drugs for treatment of HER-2 positive early breast cancer. Issued November 2006.Vorinostat (Zolinza): Treatment of cutaneous manifestations of progressive, recurrent cutaneous T-cell lymphoma. Issued October 2006.

A triplet that includes the investigational agent canfosfamide (Telcyta, Telik, Inc.) showed strong activity as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC)

The third-generation epothilone KOS-1803 may optimize tumor penetration while limiting exposure to other tissues