Research and Treatment

Cervical Cancer - Medicine in Development PDF

Cancer Quest-Information on the nature of Cancer Research and Treatment

 

WHAT'S NEW IN CERVICAL CANCER RESEARCH AND TREATMENT?

Advanced and Recurrent Cervical Cancer

This page has been made possible through an unrestricted educational grant from Glaxo Smith Kline pharmaceuticals. The NCCC wants to thank them for their efforts to bring education about cervical cancer to medical professionals and to women. And to thank the author of this information, Dr. Bradley Monk.

 

Introduction
Despite significant advancements in the screening and treatment of cervical dysplasia, cervical cancer remains a threat to thousands of women annually. In 2004, there will be approximately 10, 520 new cases of cervical cancer in the United States, with 3,900 deaths, making it the third most common caner of the female genital tract. Importantly, cervical cancer is still a major cause of death in developing countries. It is generally the number one or two cancer related killer of women among these nations, with nearly 500,000 new cases still being diagnosed worldwide every year.

 

Essentially all cancers of the cervix including non-squamous tumors (adenocarcinomas) are related to chronic infections with the human papillomavirus (HPV). Vaccines are in development (and could be available as early as 2005), that will reduce the incidence of this disease, although it will take many years to vaccinate the population and actually see a reduction in cervical cancer rates.

 

Treatments
There are two types of cells on the cervix that can become malignant, squamous cells and glandular cells. The treatment of cervical cancer depends more on the severity of the disease (staging) than the cell type. Squamous and glandular (adenocarcinomas) tumors are generally treated similarly although some feel that the adenocarcinomas have a worse prognosis when compared to the squamous type of cancer. In the United States, the majority of cervical carcinoma patients are diagnosed with early stage disease. Among the 13,458 patients with cervical carcinoma who were registered by the SEER program between 1973 and 1987, 71% were diagnosed with early disease (FIGO stage l-llA tumors). Most of these women with early lesions are cured with surgery or radiation (RT) alone. However, patients with metastatic disease or those with more advanced lesions are at significant risk of recurrence and account for the majority of cervical cancer deaths in the United States. These deaths occur despite current surgical and radiotherapy protocols.

 

Among women with the earliest stage (Stage lA1 or micro-invasive) of cervical cancer, a simple hysterectomy is generally recommended. Usual treatment of patients with stage lA2 and lB1 lesions consists of either radical hysterectomy with bilateral pelvic lymph node dissection or Radiation therapy (RT) combining two kinds of therapy, whole pelvic teletherapy with local brachytherapy (implants). These treatments work well at resolving lesions that are small and when the cells have not yet metastasized. Surgery is often preferred to radiation therapy in younger women because ovarian function is eliminated (bringing on a kind of menopause) and sexual function is often difficult following RT. In addition, other late complications of RT ( bladder damage and bowel damage) can be avoided when patients are treated with surgery alone.

 

The Southwest Oncology Group (SWOG) and Gynecologic Oncology Group (GOG), two important cancer research groups, studied the use of chemotherapy (CT) and Radiation therapy (RT) after radical hysterectomy and lymphadenectomy. This study evaluated women found to have positive pelvic pelvic lymph nodes and/or metastasis of cancer cells to the ligaments connected to the cervix (parametrium), and/or positive surgical margins. These women were randomly selected to receive either pelvic RT alone or RT in combination with CT (intravenous cisplatin and fluorouracil every three weeks for four cycles). The results of this clinical trial demonstrated that the rate of progression of the cancer and the overall survival (OS) were significantly improved with the addition of CT. Five-year survival for the group receiving both RT and CT was projected to be 81%.

 

For womwn with more advanced cervical lesions such as stages IB2 to IVA, surgery is not possible and the standard therapy involves a combination of chemotherapy and radiaition. Surgery is not feasible in this setting since it frequently reguires removal of the bladder and rectum. Thus, cisplatin administered weekly for six weeks pelvic radiation including whole pelvic teletherapy with local brachytherapy (implants) yields cure rates of 30 to 80% among women with large or advanced tumors (stage lB2-lVA) depending on stage.

 

Except in very unusual circumstances where recurrent lesions can be treated with RT or surgery (generally when located in the pelvis), almost all women who develop recurrent cervical cancer die of their disease on average after 7-10 months of palliative treatment. Until recently, the standard regimen for chemotherapy treatment in this setting has been intravenous cisplatin administered every 3 weeks. This regimen has yielded response rates in the range of 18-21% with an average survival rate of 8-9 months. Adding paclitaxel, doubling the cisplatin dose, or adding ifosfamide all have been shown to increase response rates but not to a degree that results in prolonging the survival time. The combination of paclitaxel and cisplatin was generally felt to be the most active regimen of these 3 choices increasing the response rate to 37% as well as prolonging the progression-free survival. However, because of the lack of a clear survival advantage, increased neuropathy, increased cytopenia and associated alopecia (hair loss) this combination can not be routinely recommended. Importantly, the paclitaxel and cisplatin combination was studied before cisplatin was used with radiation in treating primary lesions and radiation reduces the response rates to cisplatin.

 

Other Trials
Recently, the GOG( a prominent cancer research group) reported a randomized phase III Trial of cisplatin versus cisplatin plus topotecan in the treatment of stage IVB, recurrent or persistent cervical cancer. This study was the first to show that adding a second drug to the standard regimen of single agent cisplatin administered every 3 weeks resulted in a highly significant prolongation of survival (9.4 versus 6.5 months). In addition, this combination was found to be well tolerated and not associated with a decrease in quality of life. Interestingly, the response rate (13%) to cisplatin alone in this trial was surprisingly low and was most likely related to the new era of upfront chemo-radiation treatments. In other words, now that chemotherapy is used with radiation to treat cervical cancers initially, recurrent cancers seem to now be more resistant and respond less frequently to treatment as a result of this prior chemotherapy. However, the use of topotecan can help overcome some of these poor prognostic factors.

 

Biologic agents have not been extensively studied in this disease, however, other cisplatin like drugs have shown promise in research trials. Significant activity of carboplatin containing regimens have been reported, however, it is generally recognized that these regimens are inferior to cisplatin containing regimens based on prior GOG studies. Cisplatin containing regimens are the standard of care for recurrent cervical cancer. Cisplatin plus gemcitabine or cisplatin plus vinorelbine are currently being compared to cisplatin plus topotecan within the GOG. This four arm study also includes a paclitaxel containing regimen since the prior paclitaxel study was completed before chemotherapy was commonly added to RT, a common occurrence as mentioned above before the development of recurrent disease.

 

Summary
In summary, surgery is ideal for young healthy women with small lesions. Occasionally, radiation, usually with chemotherapy, is recommended if high risk factors are discovered during surgery. Larger tumors are treated without surgery using a combination of radical radiation (external and internal therapy) and weekly cisplatin chemotherapy. Finally, for those with recurrent, metastatic or widespread lesions (stage IVB) participation in the four arm GOG study (cisplatin+topotecan, cisplatin+gemcitabine, cisplatin+vinorelbine, cisplatin+paclitaxel) is recommended. Alternatively, cisplatin and topotecan is preferred, off study, given its survival advantage in the recently reported GOG trial.

 

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