Recurrent Ovarian Cancer as Chronic Disease

Treating recurrent ovarian cancer requires a newperspective on the disease and the objectives of therapy, according to DeborahK. Armstrong, MD, assistant professor of gynecology and obstetrics at JohnsHopkins University School of Medicine. With initial disease, the goal is toprevent recurrence. "But once we have documented a relapse for ourpatients, we have to shift gears a little bit," Dr. Armstrong said at arecent teleconference entitled, Recurrent Ovarian Cancer: State-of-the-ArtTreatments. "What is most helpful is to actually think about treatingrecurrent ovarian cancer as a chronic disease, just like you’d treat diabetesor high blood pressure."

Although recurrent ovarian cancer may go into a remission, she continued,"it’s never really going to go away completely." When remission isnot possible, the goal of treatment becomes stopping or slowing the spread ofcancer cells. As with other chronic diseases, the emphasis of treatment is ondelaying progression of the disease rather than on eliminating it altogether."We’d like to see a response, but we recognize that for some patients,particularly patients whose disease was growing quite quickly, stable disease isa benefit." She added, "Many of our treatments today have a muchhigher stable-disease rate than they do a response rate…We’d like to be ableto put everybody into another remission, but we recognize that we can’t alwaysdo that."

Minimizing Toxicity

The treatment of any chronic disease requires that a physician understand thenatural history of the illness. In addition, physicians must recognize that theprogression of disease and its manifestations will vary from patient to patient.This is also true with recurrent ovarian cancer.

The key to treating recurrent ovarian cancer is to maximize the number ofagents used while minimizing treatment-related symptoms, Dr. Armstrong said.This is best accomplished by juggling the order of the chemotherapies used. Inparticular, the physician must carefully consider how any treatment decisionsmade now will affect management of the disease later. "We need toanticipate impending decision points," Dr. Armstrong said. "Forexample, when seeing a patient, I’m thinking: If I treat that patient today,what will my choices be? If I treat that patient 6 months from now, whatwill my choices be then? And [those choices] are sometimes quitedifferent."

Four Key Drugs

Four drugs have been shown to be effective in patients who relapse within1 year of initial treatment with platinum-based drugs and taxanes. Thesedrugs are topotecan (Hycamtin), liposomal doxorubicin (Doxil), etoposide, andgemcitabine (Gemzar). "I tell patients that under ideal circumstances, we’regoing to use all of these agents at one time or another," Dr. Armstrongsaid. "The question isn’t which one of these agents to use, but whatorder we should use them in."

Juggling the order of drug administration is necessary to reduce toxicity.Topotecan, for example, lowers the red blood cell count. Thus, it is better usedas a second or third treatment than as a fourth or fifth treatment, she said.Liposomal doxorubicin, on the other hand, does not lower the red blood count, soit is safe to use as the fourth or fifth treatment.

Similarly, the use of platinum-based drugs and taxanes as second-line therapymust be timed properly for optimum efficacy. "If it’s a very short time—3to 6 months from the completion of the initial therapy—the disease doesn’thave a very high chance of responding to retreatment with those agents,"Dr. Armstrong said. "If you can defer those therapies until down the line,the chance of responding is actually going to go up." Cancer cells thatremain after initial treatment tend to be resistant to the platinum drugs andthe taxanes, but that resistance diminishes with time.

If cancer cells are not exposed to platinum drugs or taxanes for 12 to 18months, the chance that they will respond to these agents increases. In theinterim, another drug can be administered, Dr. Armstrong said. Patients may havedifficulty understanding this strategy. "Sometimes the knee-jerk reactionis to say, ‘I did real well, I had a nice response to paclitaxel and platinumup-front, let’s use that again.’ But what you’re treating now isdifferent. It’s disease that has survived through paclitaxel andplatinum."

Older drugs, such as tamoxifen, ifosfamide (Ifex), altretamine (Hexalen), andvinorelbine (Navelbine) may also be useful in recurrent disease, but the dataregarding their efficacy are older and predate the availability of newer drugs.For this reason, Dr. Armstrong said, "I don’t know how to comparethem."

Cumulative Risk

Without a carefully considered plan, the patient is at risk of cumulativetoxicity. "We have to appreciate that overtreatment can be as dangerous andinappropriate as undertreatment," Dr. Armstrong said. She added that shehas seen patients who had few symptoms from their recurrent cancer but who were"really suffering" from their treatment. Patients with cumulativetoxicities also face increased time between treatments or dose reductions. Boththese measures diminish the effectiveness of chemotherapy.

The nature of chronic disease makes it essential that patients be involved intheir own care. "Patients need to be able to participate in thedecision-making process," Dr. Armstrong said. "For any chronicdisease, this is essential; for ovarian cancer, I think it’s particularlyimportant. Patients need to be able to set goals for their therapy and to haverealistic expectations. As physicians, it’s our job to educate patients withregard to treatment options."

New Agents

Targeted, or biological, agents are among the most promising new drugscurrently in clinical trials, Dr. Armstrong said. Unlike chemotherapies, thesedrugs are enzyme inhibitors that block growth-factor pathways. Trastuzumab(Herceptin), approved for breast cancer, and imatinib mesylate (Gleevec),approved for chronic myelogenous leukemia (CML), are examples of targetedtherapies.

Trastuzumab may also play a role in the treatment of recurrent ovarian cancerfor the 10% to 15% of patients who overexpress the growth factor HER2. Theusefulness of this antibody therapy is better understood in breast cancer thanovarian cancer, Dr. Armstrong noted. Breast cancer data show that whentrastuzumab is combined with paclitaxel, docetaxel, gemcitabine, or vinorelbine,the drugs work more effectively. When combined with doxorubicin, however, itcauses unacceptable toxicity. Trastuzumab has not been approved by the US Foodand Drug Administration for the treatment of ovarian cancer, and therefore, someinsurance companies will not reimburse its use, she cautioned.

For More Information

The free teleconference was cosponsored by Cancer Care, Inc, and the OvarianCancer National Alliance, with an educational grant from Glaxo SmithKlineOncology. Cancer Care can be reached at 800-813-HOPE and www.cancercare.org. TheOvarian Cancer National Alliance can be reached at 202-331-1332 and www.ovariancancer.org. Participation in the teleconference was offered to womenliving with ovarian cancer, their families, and friends, as well as tohealth-care professionals.