Cervical Cancer

SAN FRANCISCO-In a large phase III study, a prophylactic human papillomavirus (HPV) vaccine prevented 100% of high-grade cervical precancers and noninvasive adenocarcinomas associated with HPV types 16 and 18. Laura Koutsky, PhD, of the University of Washington, Seattle, presented the results for the FUTURE II Steering Committee at a late-breaking abstract session of the Infectious Diseases Society of America annual meeting.

Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

Over the past four decades, the incidence and mortality rates for uterine cervical carcinoma have decreased in the United States by as much as 70% to 75% [1]. This improvement is among the largest seen for any cancer site and has been attributed to the use of cervical cytologic screening [2].

Pemetrexed (Alimta) is a novel antimetabolite that inhibits the folatedependentenzymes thymidylate synthase, dihydrofolate reductase, andglycinamide ribonucleotide formyltransferase. Pemetrexed has demonstratedactivity in clinical trials in a variety of tumor types, includinglung, breast, colon, mesothelioma, pancreatic, gastric, bladder, headand neck, and cervix. Pemetrexed is rapidly metabolized into activepolyglutamate forms that are potent inhibitors of several tetrahydrofolatecofactor-requiring enzymes critical to the synthesis of purines and thymidine.Functionally, pemetrexed acts as a prodrug for its polyglutamateforms. Two different transporters are known to take extracellular folates,and some antifolates, into the cell. These are the reduced folate carrierand the folate receptor. One of the many attributes that make pemetrexedunique is that methodology has been developed to eliminate and controlmany of its associated clinical toxicities. Multivariate analyses demonstratedthat pretreatment total plasma homocysteine levels significantlypredicted severe thrombocytopenia and neutropenia, with orwithout associated grade 3/4 diarrhea, mucositis, or infection. Routinevitamin B12 and folic acid supplementation have resulted in decreasedfrequency/severity of toxicities associated with pemetrexed without affectingefficacy, making this novel antifolate a safe and efficaciousanticancer agent.

Pemetrexed (Alimta) is active in a variety of solid tumors, includingbreast and gynecologic cancers. Phase II trials of pemetrexed at a doseof 600 mg/m2 without vitamin B12 and folic acid supplementation inlargely pretreated metastatic breast cancer patients demonstrated objectiveresponse rates of 21% and 28%, with generally manageableneutropenia constituting the primary toxicity. In phase II trials using500 mg/m2 with or without vitamin supplementation in anthracyclineandtaxane-pretreated patients, response rates were lower (approximately9%) and treatment was generally well tolerated irrespective ofvitamin supplementation status. A phase II trial is currently comparingpemetrexed doses of 600 and 900 mg/m2 with vitamin B12 supplementationin patients with previously untreated advanced breast cancer. In aphase II trial in patients with advanced cervical cancer, pemetrexed at600 mg/m2 without vitamin supplementation and 500 mg/m2 with supplementationproduced similar response rates, with the frequency of neutropeniabeing somewhat lower among patients receiving the lower doseand vitamin supplementation. Preliminary results in an ongoing phaseII trial indicate activity of the regimen of gemcitabine (Gemzar) at1,000 mg/m2 plus pemetrexed at 500 mg/m2 with vitamin supplementationin patients with ovarian cancer. Ongoing and future studies willestablish optimal dosing regimens of pemetrexed and potential benefitsof vitamin supplementation in the settings of metastatic breastcancer and gynecologic malignancies.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

WASHINGTON-The 2004 US Surgeon General’s report on the health risks of smoking adds five cancers to the list of diseases caused by cigarettes-acute myeloid leukemia, and stomach, pancreatic, cervical, and kidney cancers. Other newly

SAN DIEGO-For the first time, a combination regimen has shown improved survival over single-agent cisplatin (Platinol) for the treatment of advanced cervical cancer, according to the Gynecologic Oncology Group (GOG) protocol 179, which was presented at the 35th Annual Meeting of the Society of Gynecologic Oncologists (abstract 9).

A review of sentinel node mapping in vulvar and cervical cancer, a technique intended to reduced lymphadenectomy-associated morbidity, and the related controversies.

Iwould like to compliment the authorson an excellent review ofsentinel node evaluation in gynecologiccancer-in particular, vulvarand cervical cancer. The authors havebeen at the forefront of minimally invasivesurgery for gynecologicmalignancies. They have publishedextensively about their experiencewith laparoscopy and radical trachelectomy.Now this group brings forthanother technique that may revolutionizethe way we treat women withvulvar and cervical carcinoma.

Cervical cancer rates have fallen in the United States; regardless, thedisease remains a significant concern for women, especially those whoare premenopausal. The management of cervical cancer is dependenton stage of disease at diagnosis, and specific needs emerge for patientsboth during and following treatment. Over the past decade, the focus hasbeen to maintain adequate tumor control while reducing long-termnegative consequences. However, problems with sexuality and fertilitypersist for women treated for cervical cancer despite these advances.Sexual dysfunction following treatment for gynecologic cancer hasbeen well documented in the literature, and recent studies demonstratethe success of brief psychosexual interventions. Treatment of sexualdifficulties in cancer patients can be achieved through the provision ofinformation, support, and symptom management, ideally as part of asexual health program. Resources are not always available to developsuch a program. However, medical professionals can identify individualsand organizations with expertise in treating sexual and fertilityconcerns, which can be provided to their patients, making help withthese problems more accessible as needs arise.

Carter et al provide a nice summaryof current knowledge ofsexual dysfunction in and rehabilitationof women with invasivecervical cancer. The prevailing perspectiveof their review, however,seems to be that most women treatedfor cervical cancer are white, middleclasspatients at major cancer centers.In order to make a difference in thequality of life of the majority of cervicalcancer survivors, we have to understandwho they are and recognizethe impact of social and gender inequalityon their lives and relationships.

The importance of quality of lifeduring and after treatment forcervical cancer has been ignoredfor too long. The pervasive attitudethat focuses on cure, withmorbidity an afterthought, is stillparamount in many patients’ and oncologists’minds. However, at the insistenceof patients and families, manyclinicians have recognized and startedto address these issues over thepast 2 decades.

BETHESDA, Maryland-Two phase III studies involving tens of thousands of women should indicate before this decade’s end whether a vaccine aimed at preventing infection by two cancer-causing strains of human papillo-mavirus (HPV) will likely reduce the incidence and mortality of cervical cancer, and perhaps several other cancers as well.

Two cancer-related issues-evidence-based cancer screening andpain control in advanced cancer-are among 20 priority areasthat an Institute of Medicine (IOM) committee has urged publicand private organizations to focus on as a way of transforming healthcare in the United States. Goals regarding screening, especially forcolorectal and cervical cancer, the report said, are "to increase thenumber of people who receive screenings and to provide timely followup."Regarding pain control in patients with advanced cancer, thecommittee urged efforts to "emphasize cooperation in protocols acrosscare settings, advance planning for changes in settings, as well asheightened pain, and public education regarding the merits of opioidmedications in this area."

Anal cancer accounts for 1.5% of digestive system malignancies inthe United States. In the past 30 years, substantial progress has beenmade in understanding the pathophysiology and treatment of thedisease. Anal cancer was once believed to be caused by chronic localinflammation of the perianal area, and treatment was abdominoperinealresection. From epidemiologic and clinical studies, we nowknow that the development of anal cancer is associated with humanpapillomavirus infection and that the disease has a pathophysiologysimilar to that of cervical cancer. Less invasive treatments have alsobeen developed, and the majority of patients with anal cancer can nowbe cured with preservation of the anal sphincter using concurrentexternal-beam radiation therapy and fluorouracil (5-FU)/mitomycin(Mutamycin) chemotherapy. Current areas under investigation includethe incorporation of platinum agents into the chemotherapyregimen and the use of cytologic screening studies for high-riskpopulations.

NEW ORLEANS-In women with locally advanced cervical cancer, smoking is an independent risk factor for a significantly worse outcome, a new study from the Gynecologic Oncology Group (GOG) has shown.

ROCKVILLE, Maryland-Physicians can discontinue cervical cancer screening for many women age 65 and older, and delay screening for some young women until age 21, according to new guidelines developed by the US Preventive Services Task Force (USPSTF).