WASHINGTONNew diagnostic tests and effective second-line
chemotherapeutic agents may transform ovarian cancer from a certain
killer into a chronic disease capable of being managed with
medications that are easy to administer, provide good quality of
life, and reliably quash recurrences of disease, said Patricia
Goldman and Agustin Garcia, MD.
Ms. Goldman, president of the Ovarian Cancer National Alliance, and
Dr. Garcia, a medical oncologist at the Kenneth Norris, Jr.,
Comprehensive Cancer Center, University of Southern California, Los
Angeles, spoke during a telephone briefing preceding the annual
conference of the Ovarian Cancer National Alliance.
Because of the development of tests that catch ovarian
cancer earlier and new drugs for treating recurrences, women with
ovarian cancer will be surviving beyond the time that was
anticipated, and they will be able to lead full and active
lives, Ms. Goldman said.
Dr. Garcia added, There are many new drugs that are being
developed as pills; so in the future a woman may not even have to go
to her doctors office or into the hospital for chemotherapy to
treat disease recurrences. She may be able to pick up a prescription
for two or three chemotherapeutic drugs, take some pills once a day,
and thats it.
Standard chemotherapy for ovarian cancer, which involves paclitaxel
(Taxol) and cisplatin (Platinol) or carboplatin (Paraplatin), can
shrink tumors in about 80% of women. The life expectancy following
treatment, nevertheless, is only about 3 years, because the disease
most commonly is diagnosed at an advanced stage.
Ovarian tumors, particularly those that arise between the vagina and
rectum, frequently escape detection with routine pelvic or rectal
examination. Blood testing for CA 125 signals the presence of ovarian
cancer in as many as 80% of women with stage III or IV disease, but
only about 50% of women with stage I disease.
Two promising new diagnostic tests are being evaluated in an ongoing
multicenter clinical trial that will enroll 5,000 women at high risk
for ovarian cancer and 1,000 women with newly diagnosed disease.
The first is a blood test that screens for the presence of
lysophospholipic acid (LPA), a recently discovered marker for ovarian
cancer that may be related to the process of angiogenesis in
malignant tumors. An initial clinical trial conducted by the
Cleveland Clinic involved 48 women with ovarian cancer and
approximately 100 controls (healthy women or women with other kinds
of tumors). The results indicated that LPA might detect early ovarian
cancer, Dr. Garcia said.
LPA appears to be elevated in women with early ovarian cancer,
so the hope is that LPA will be like PSA for prostate cancer in men.
It will be elevated in women with an early form of the disease that
can be cured with current therapy in 90% of cases, he said.
The second diagnostic strategy involves Pap smear
sampling of the ovaries to obtain cells for pathologic analysis. This
is done by ultrasound-guided, needle-directed brushing of the surface
of the ovary. If the Pap smear for the ovaries proves to
be able to detect ovarian tumors as well as its counterpart detects
cervical cancer, it might be done as a screening measure in every
woman every 4 or 5 years, Dr. Garcia suggested.
The Pap smear strategy is being assessed in a study headed by David
A. Fishman, MD, of the Robert H. Lurie Cancer Center, Northwestern
University. Dr. Fishman is also involved in the development of LPA,
in collaboration with Atairgin Technologies, Irvine, Ca.
Newer chemotherapeutic drugs, such as topotecan (Hycamtin) and
liposomal doxorubicin (Doxil), have been effective in the treatment
of women after the first recurrence of ovarian cancer. In a European
trial conducted about 5 years ago, topotecan was as effective as
paclitaxel in treating women whose cancer recurred after a course of
platinum-based therapy, he said.
Liposomal doxorubicin elicited one complete and eight partial
clinical responses in 35 women who failed to respond to platinum and
paclitaxel. Seven of the responses were durable; they were confirmed
in two consecutive CT scans, he said.
Liposomal doxorubicin also produced a median disease-free survival of
5.7 months, and an overall median survival of 11 months with minimal
side effects (J Clin Oncol 15:987-993, 1997).
A trial comparing the liposomal form of doxorubicin and topotecan
indicated that the two drugs had nearly identical efficacy, although
liposomal doxorubicin produced fewer serious side effects, Dr. Garcia said.
Some of the chemotherapeutic drugs that are being developed for the
treatment of ovarian cancer, such as liposomal doxorubicin, have
fewer side effects than paclitaxel and the platinums. Because
liposomal doxorubicin is encased in microscopic packets of fat, the
drug does not exert its effect until it passes into malignant tumors
from the blood vessels that feed them. As a result, the liposomal
form of doxorubicin causes little or no hair loss, nausea, or
vomiting and only slight myelosuppression.
He noted that these newer anticancer drugs will not immediately
replace conventional platinum-based therapy for ovarian cancer.
It will take some time before we can disregard platinum because
platinum is a very effective drug, he said. So in the
next few years, we will be adding new drugs to the treatment of
ovarian cancer. We may add gemcitabine [Gemzar], which has very few
side effects, to current paclitaxel and platinum regimens.
Newer treatment regimens may be given sequentially, he said. A
patient may receive four cycles of topotecan and cisplatin, then four
cycles of paclitaxel and carboplatin. So the patient will get
multiple drugs as initial therapy but with manageable side
effects, he said.
An international clinical study will be assessing whether some of
todays second-line chemotherapeutic drugs can move to the front
lines of ovarian cancer treatment, Dr. Garcia said. The study will be
randomizing between 5,000 and 6,000 women to several treatment arms:
conventional carboplatin/paclitaxel vs gemcitabine;
carboplatin/paclitaxel vs liposomal doxorubicin; four cycles of
carboplatin/topotecan followed by four cycles of
carboplatin/paclitaxel; four cycles of carboplatin/gemcitabine
followed by four cycles of carboplatin/paclitaxel.
Other Treatment Approaches
Ovarian cancer also may be amenable to other treatment approaches,
such as gene therapy and antiangiogenesis drugs. Gene therapy for the
treatment of some malignancies has been hampered because the immune
system destroys intravenously administered gene vectors.
Ovarian cancer tends to be limited to the abdominal cavity. It
may respond to gene therapy that is administered directly to the
abdominal cavity through a catheter because the gene therapy would
not need to get into the bloodstream to arrive at a tumor, Dr.
Garcia pointed out.
Antiangiogenesis drugs may prevent further growth of tumors in women
who still have ovarian cancer after surgery to decrease tumor volume
and chemotherapy. Antiangiogenesis drugs might not destroy
ovarian cancer or completely cure a patient, but they could be one of
the ways of making ovarian cancer a chronic disease, Dr. Garcia
said. For example, in diseases such as hypertension, patients take a
nontoxic medication to prevent spikes of high blood pressure. In
the future, antiangiogenesis drugs may be given to women who are in
remission from ovarian cancer to prevent the cancer from coming
back, he said.
At present, women who have achieved complete remission of ovarian
cancer are being randomized to receive either gene therapy or no
treatment in phase III clinical trials. Antiangiogenesis drugs are
currently in phase I/II trials of ovarian cancer, and some will enter
phase III trials in the near future, Dr. Garcia said.