A major challenge in treating ovarian cancer is that by the time most patients are diagnosed with the disease, it has already progressed to stage III or IV. The difficult-to-examine location of the ovaries deep in the pelvis tends to prevent physicians from detecting ovarian cancer at a more curable stage. Until recently, patients with the disease were often thought to exhibit no symptoms during the earliest stages of the disease. Recent studies have demonstrated that certain symptoms are more common in women with ovarian cancer when compared with women in the general population. Up to 90% of women with the disease will experience symptoms earlier. Symptoms suggestive of ovarian cancer include bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and urinary symptoms (urgency or frequency), particularly if the symptoms are new (onset within the past year) and frequent (occurring more than 12 days per month). However, these symptoms are non-specific and are often mistaken for other conditions. Awareness of symptoms may allow physicians to detect ovarian cancer earlier.

The National Comprehensive Cancer Network (NCCN) recently released clinical practice guidelines in oncology for ovarian cancer. One of the new revisions is an emphasis on the possibility that early-stage symptoms of ovarian cancer may be present. “Improving screening methods and early detection remain the key for women with ovarian cancer,” says Robert J. Morgan, Jr., MD, FACP who chaired the NCCN panel that developed the guidelines.

Managing Allergic Reactions

Chemotherapy drugs have the potential to cause infusion reactions, either during an infusion or following completion of an infusion. Reactions to platinum drugs (eg, carboplatin and cisplatin) tend to occur following re-exposure to the drug. About 75% to 80% of patients with stage III or IV ovarian cancer will experience recurrence, which can occur at any time—during treatment, within 6 months of completing treatment, or more than a year after completing treatment. “This often results in patients being retreated with the same chemotherapeutic agent,” says Dr. Morgan. “Over the past few years, physicians have recognized that more patients are developing allergies to platinum-based chemotherapies. Because platinum drugs are still the most important agents for treating ovarian cancer, developing a strategy to derive benefits from these drugs is critical even though the risk for allergies persists.”

The NCCN guidelines provide information on allergic reactions and recommendations on desensitization regimens. The protocols include signs and symptoms of infusion reactions, preparations for potential reactions, and advice for dealing with allergies once they occur. The guidelines recommend administering small doses of medication during a 4-to-13 hour infusion to overcome allergic reactions.

Chemotherapy for Recurrent Ovarian Cancer

A new element in the guidelines is the inclusion of recommendations for appropriate recurrence therapy based on the timing of recurrence and the addition of new agents, most notably pemetrexed, as a potential therapy for recurrent disease. Current research suggests that this drug may be effective alone or in combination when treating patients with recurrent ovarian cancer.

Principles of Chemotherapy Updated

Another addition to the NCCN guidelines includes a new “Principles of Chemotherapy” section (Table 1). “Patients should be informed about the different treatment options available,” says Dr. Morgan, “particularly IV and IV/intraperitoneal (IP) chemotherapy, as well as the benefits and risks of this approach compared with IV chemotherapy alone. Experts also emphasize that patients should be encouraged to participate in clinical trials during all aspects of their treatment. In patients who have been optimally debulked with surgery, a peritoneal catheter should be considered during subsequent chemotherapy. This catheter allows for direct administration of drugs to the area of the disease. Recent data have shown that IP chemotherapy can be of substantial benefit and improves overall survival among patients with stage III ovarian cancer.”

New updates to the NCCN guidelines also include recommendations regarding the timing of primary surgery. Completion surgery for patients responsive to chemotherapy with initially unresectable residual disease should be considered depending on tumor response and potential resectability in selected patients (Table 2). “This section of the guidelines also provides recommendations on particular circumstances, such as minimally-invasive surgery and fertility sparing procedures,” Dr. Morgan says. He adds that there has been steady progress in the treatment of ovarian cancer, particularly with the continued development of new drugs and targeted agents. “However, more clinical trials are necessary to investigate the role of targeted agents alone and in combination among women with newly diagnosed and recurrent ovarian cancer.”

References

NCCN Practice Guidelines in Oncology – v.2.2009 Ovarian Cancer. Presented March 14, 2009 at the National Comprehensive Cancer Network (NCCN) 14th Annual Conference. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

Matulonis UA, Horowitz NS, Campos SM, et al. Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer. J Clin Oncol. 2008;26:5761-5766.

Gasent Blesa JM, Alberola Candel V, Provencio Pulla M, et al. Management of platinum-resistant ovarian cancer with the combination of pemetrexed and gemcitabine. Clin Transl Oncol. 2009;11:35-40.

Brun JL, Rouzier R, Selle F, et al. Neoadjuvant chemotherapy or primary surgery for stage III/IV ovarian cancer: contribution of diagnostic laparoscopy. BMC Cancer. 2009;9:171.

Milczek T, Klasa-Mazurkiewicz D, Emerich J, Kobierski J. Second line platinum-based intraperitoneal chemotherapy for advanced ovarian cancer. Acta Obstet Gynecol Scand. 2009;88:463-467.