Ovarian Cancer

Anti-EGFR (epidermal growth factor receptor) therapies, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, demonstrate activity in a variety of tumor types. While both inhibit the EGFR pathway, they act via different mechanisms.

Overexpression of the epidermal growth factor receptor (EGFR) is correlated with poor prognosis in many human cancers. Two main classes of anticancer agents affect the EGFR: those targeting the extracellular ligand-binding domain and those that block the intracellular tyrosine kinase (TK) domain. Cetuximab (Erbitux) is a mouse/human chimeric monoclonal antibody that targets the ligand-binding domain of the EGFR, whereas erlotinib (Tarceva) and gefitinib (Iressa) are small-molecule TK inhibitors. Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Given the common pathway through which these agents work, some adverse events are similar. Many patients treated with these agents develop an acne-like rash on the face and upper body, most likely related to keratinocyte alterations and hair follicle proliferation and maturation. Although clinical manifestation of this reaction closely resembles acne vulgaris, the histology is more similar to infectious folliculitis. Other adverse events appear to be related to a drug class or individual agent. For example, interstitial lung disease is a rare but potentially fatal reaction that has been reported with gefitinib. Hypomagnesemia reported in association with cetuximab may be related to EGFR blockade in the kidney. Anaphylactic or anaphylactoid infusion reactions are also seen with cetuximab, as with other monoclonal antibodies.

The FDA's Oncologic Drugs Advisory Committee (ODAC) declined to recommend that the agency approve Gemzar (gemcitabine, Eli Lilly) in combination with carboplatin for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.

Two analyses from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) MA.17 letrozole (Femara) trial strongly support the ability of this aromatase inhibitor to significantly reduce disease recurrence among postmenopausal women previously treated with tamoxifen.

Over the past 2 decades, we have seen major progress in the management of women with ovarian cancer, with improvements in both overall survival and quality of life. To truly appreciate this progress, it is important to understand the state of affairs regarding the treatment of ovarian cancer in the early 1980s. This paper will discuss that historical background, describe the increasingly favorable impact of evolving treatment paradigms in ovarian cancer, and note future directions for clinical research in this complex disease process.

Over the past 2 decades, we have seen major progress in the management of women with ovarian cancer, with improvements in both overall survival and quality of life. To truly appreciate this progress, it is important to understand the state of affairs regarding the treatment of ovarian cancer in the early 1980s. This paper will discuss that historical background, describe the increasingly favorable impact of evolving treatment paradigms in ovarian cancer, and note future directions for clinical research in this complex disease process.

Over the past 2 decades, we have seen major progress in the management of women with ovarian cancer, with improvements in both overall survival and quality of life. To truly appreciate this progress, it is important to understand the state of affairs regarding the treatment of ovarian cancer in the early 1980s. This paper will discuss that historical background, describe the increasingly favorable impact of evolving treatment paradigms in ovarian cancer, and note future directions for clinical research in this complex disease process.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

The epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.

In both chemonaive and heavily pretreated patients with non-small-cell lung cancer (NSCLC), investigations of canfosfamide (TLK286, Telcyta) are yielding "exciting" findings, Howard A. Burris III, MD, reported at the Chemotherapy Foundation Symposium XXIII (abstract 7).

Even an allergic reaction to a chemotherapeutic agent does not always preclude future administration of that drug. In some cases, few other options exist. Michelle J. Ciszewski, RN, BSN, OCN, discussed a desensitization protocol successfully used at her facility during the Oncology Nursing Society 30th Annual Congress (abstract 59).

In a clinical announcement, the National Cancer Institute (NCI), supported by six professional societies and advocacy groups, has urged physicians to use a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy to treat women with advanced ovarian cancer.

The herbal supplement gingko biloba appeared to lower the risk of ovarian cancer in an epidemiologic study, while laboratory studies showed that two of the herb's components caused ovarian cancer cells to stop growing. The studies were presented at the annual fall prevention meeting of the American Association for Cancer Research (abstract 3654).

With the aging of the Western population, cancer in the older person is becoming increasingly common. After considering the relatively brief history of geriatric oncology, this article explores the causes and clinical implications of the association between cancer and aging. Age is a risk factor for cancer due to the duration of carcinogenesis, the vulnerability of aging tissues to environmental carcinogens, and other bodily changes that favor the development and the growth of cancer. Age may also influence cancer biology: Some tumors become more aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging. Aging implies a reduced life expectancy and limited tolerance to stress. A comprehensive geriatric assessment (CGA) indicates which patients are more likely to benefit from cytotoxic treatment. Some physiologic changes (including reduced glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis, and cardiac and neurotoxicity) are common in persons aged 65 years and older. The administration of chemotherapy to older cancer patients involves adjustment of the dose to renal function, prophylactic use of myelopoietic growth factors, maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age is not a contraindication to cancer treatment: With appropriate caution, older individuals may benefit from cytotoxic chemotherapy to the same extent as the youngest patients.

With the aging of the Western population, cancer in the older person is becoming increasingly common. After considering the relatively brief history of geriatric oncology, this article explores the causes and clinical implications of the association between cancer and aging. Age is a risk factor for cancer due to the duration of carcinogenesis, the vulnerability of aging tissues to environmental carcinogens, and other bodily changes that favor the development and the growth of cancer. Age may also influence cancer biology: Some tumors become more aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging. Aging implies a reduced life expectancy and limited tolerance to stress. A comprehensive geriatric assessment (CGA) indicates which patients are more likely to benefit from cytotoxic treatment. Some physiologic changes (including reduced glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis, and cardiac and neurotoxicity) are common in persons aged 65 years and older. The administration of chemotherapy to older cancer patients involves adjustment of the dose to renal function, prophylactic use of myelopoietic growth factors, maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age is not a contraindication to cancer treatment: With appropriate caution, older individuals may benefit from cytotoxic chemotherapy to the same extent as the youngest patients.

With the aging of the Western population, cancer in the older person is becoming increasingly common. After considering the relatively brief history of geriatric oncology, this article explores the causes and clinical implications of the association between cancer and aging. Age is a risk factor for cancer due to the duration of carcinogenesis, the vulnerability of aging tissues to environmental carcinogens, and other bodily changes that favor the development and the growth of cancer. Age may also influence cancer biology: Some tumors become more aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging. Aging implies a reduced life expectancy and limited tolerance to stress. A comprehensive geriatric assessment (CGA) indicates which patients are more likely to benefit from cytotoxic treatment. Some physiologic changes (including reduced glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis, and cardiac and neurotoxicity) are common in persons aged 65 years and older. The administration of chemotherapy to older cancer patients involves adjustment of the dose to renal function, prophylactic use of myelopoietic growth factors, maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age is not a contraindication to cancer treatment: With appropriate caution, older individuals may benefit from cytotoxic chemotherapy to the same extent as the youngest patients.

Traditionally, most hereditarynonpolyposis colorectal cancer(HNPCC) syndrome patientshave been identified and cared for bygastroenterologists, colorectal surgeons,and gastrointestinal medicaloncologists. Hence, the realization thatgynecologic tumors actually play amajor role in HNPCC has come relativelylate. Consequently, much of theclinical and basic science focus ofresearch in HNPCC has concentratedon colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomaldominant cancer susceptibility syndrome associated with inheriteddefects in the DNA mismatch repair system. HNPCC family membersare at high risk for developing colorectal, endometrial, and ovariancancers. Studies of HNPCC families have helped define the importantrole that mismatch repair genes play in the molecular pathogenesis ofendometrial and ovarian cancers. This review will describe some of theimportant clinical and molecular features of HNPCC-related endometrialand ovarian cancer and describe how genetic susceptibility can beidentified in patients with sporadic endometrial and ovarian cancers. Itis important to identify patients with HNPCC, as families of mutationcarriers may benefit from genetic counseling, testing, and intensifiedcancer surveillance.

In their article, Taylor and Mutchbring attention to the gynecologiccancer risks associated with hereditarynonpolyposis colorectal cancer(HNPCC).[1] The identificationof individuals and families at risk forHNPCC has often focused on the coloncancer phenotype, but the diagnosisof endometrial or ovarian cancershould also be considered.

The review by Vergote et al[1]presents a well-organized andcomprehensive summary of thedata addressing neoadjuvant chemotherapyfor ovarian cancer. The timingof debulking surgery for thisdisease is a common and clinicallyimportant question, but one that lacksdefinitive trial data. The assembleddata suggest a rationale for decisionmaking.The European Organizationfor Research and Treatment of Cancer(EORTC) and Gynecologic OncologyGroup (GOG) 152 trialspresent compelling evidence supportinga “maximal surgical effort” by anexperienced gynecologic surgeon,preferably at a specialty hospital, atsome point during primary therapy.

Because of the high rate of distant disease recurrence, the 5-yearsurvival of patients who have undergone complete surgical resectionof localized non–small-cell lung cancer (NSCLC) is approximately 50%.Initial results from early studies of adjuvant postoperative chemotherapyreported an adverse effect of alkylating agent and older chemotherapyregimens on survival. Cisplatin-based combinations were the first toshow a survival advantage. A 1995 meta-analysis of these studies suggesteda 13% reduction in the hazard ratio for death (HR = 0.87), leadingto a 5% survival benefit at 5 years. Still, these trials involved limitednumbers of patients (N = 1,394), and the results failed to reach statisticalsignificance (P = .08). Of the five largest subsequent randomizedtrials of platinum-based adjuvant therapy, three showed a significantsurvival advantage. Although it is impossible to determine the reasonsfor the differing outcomes of these studies, several key features distinguishthem, and the data suggest that medically fit patients with resectedstage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.

Neoadjuvant, or induction, chemotherapyhas been usedextensively in selected carcinomas,particularly head andneck cancer (recently reviewed inONCOLOGY)[1] and locally advancedbreast cancer. Despite beneficialeffects on morbidity, long-termsurvival has not been significantly improvedby neoadjuvant chemotherapy.

Primary debulking surgery by a gynecologic oncologist remains thestandard of care in advanced ovarian cancer. Optimal debulking surgeryshould be defined as no residual tumor load. In retrospective analyses,neoadjuvant chemotherapy followed by interval debulking surgerydoes not seem to worsen prognosis compared to primary debulking surgeryfollowed by chemotherapy. However, we will have to wait for theresults of future randomized trials to know whether neoadjuvant chemotherapyfollowed by interval debulking surgery is as good as primarydebulking surgery in stage IIIC and IV patients. Interval debulking isdefined as an operation performed after a short course of induction chemotherapy.Based on the randomized European Organization for Researchand Treatment of Cancer–Gynecological Cancer Group (EORTC-GCG)trial, interval debulking by an experienced surgeon improves survival insome patients who did not undergo optimal primary debulking surgery.Based on Gynecologic Oncology Group (GOG) 152 data, intervaldebulking surgery does not seem to be indicated in patients who underwentprimarily a maximal surgical effort by a gynecologic oncologist.Open laparoscopy is probably the most valuable tool for evaluating theoperability primarily or at the time of interval debulking surgery.

Few would question the statementthat the role of surgery in themanagement of epithelial ovariancancer is unique in solid tumoroncology.