New Therapies Could Make Ovarian Cancer a ‘Chronic’ Disease

NEW YORK—Ovarian cancer is on its way to becoming a chronic disease, William P. McGuire III, MD, said at a press conference of the advocacy group, Ovarian Cancer National Alliance.

“I think the important aspect of ovarian cancer that is different now than it was even 10 years ago is that we are really beginning to think of this as a chronic disease rather than as a rapidly fatal one, and this is due to the number of drugs that are now available,” said Dr. McGuire, section chief, Therapeutics and Research, Gynecologic Oncology Center, Mercy Medical Center, Baltimore.

The standard primary treatment, he said, remains a platinum and a taxane, usually carboplatin (Paraplatin) and paclitaxel (Taxol). But over the last 5 years, at least seven new drugs have come to market that have proved effective against the disease, though not all are marketed for ovarian cancer per se.

Topotecan (Hycamtin) and most recently Doxil (liposomal doxorubicin) are two newer agents indicated specifically for ovarian cancer, he said. Others that have proved effective are gemcitabine (Gemzar), which is approved for use in pancreatic cancer, and oral etoposide, typically used in the treatment of lung cancer and testes cancer.

“What we would really like is to take these other drugs and move them into initial treatment, in combination with the standard treatment,” Dr. McGuire said. But that is easier said than done, he hastened to add. “When you begin to use three drugs together, you run into overlapping toxicities that often make it difficult, if not impossible, to get in adequate doses of any of the three drugs.”

One approach that is being evaluated, he said, is “sequential doublets” in which the patient is treated with two drugs and later with two different drugs. Also under study is how to utilize angiogenesis inhibitors and other inhibitory agents.

“Most ovarian cancer patients are wedded to the CA-125,” Dr. McGuire said. “When the level goes up on a regular basis, they know, for all intents and purposes, they are destined to develop recurrent ovarian cancer. It may be in a few months, but it also could be 3 years.”

Many of those patients, appropriately so, do not want to sit and just watch the CA-125 go up, he continued. “They want to do something about it, even though the tumor itself may not be visible or palpable and may not, in fact, even be causing them symptoms,” he said.

The cytostatic agents, agents that prevent cells from growing, he said, are best evaluated in a situation “where we know that a few tumor cells are beginning to reactivate.” He envisions a scenario “in the not too distant future of taking the best cytotoxic agents we have, treating the patient into a complete clinical remission with the full knowledge that a large percentage will not stay in that complete remission, and then utilizing some of the cytostatic agents that are just coming to the fore to try to maintain that complete response.”

Ultimately, he said, this strategy could lead to cure in a larger percentage of patients. “Unfortunately,” he continued, “when treating a patient with recurrent ovarian cancer, we know the disease will eventually take the patient’s life. It may be 5 years. It may be 10 years. Still, I have a large number of patients whom I’ve been treating for 15 years, which gets me back to the point that needs to be made, that this is becoming a chronic disease.”

Just as a combination of agents may provide the best treatment for recurrent disease, a combination of markers may be the best way to detect early disease, Gordon Mills, MD, chairman of molecular therapeutics, M.D. Anderson Cancer Center, said at the briefing.

“We predict that a combination of the known marker for ovarian cancer, CA-125 and the newly emerging markers—LPA (lysophosphatidic acid), HERB2, TAg(t antigen), MCSF, and OCSF1—may, together, have sufficient sensitivity to identify patients who have early ovarian cancer or a greatly increased chance of having it. They will need a follow-up test, just as mammography is followed up with biopsy, or a Pap smear is followed up with colposcopy.”

Transvaginal ultrasound, the current follow-up test for ovarian cancer, does not have adequate sensitivity, he said. However, he added, a new possible follow-up test, involving a microinvasive technique to remove cells from the surface of the ovary, is under development.