Using a drug off-label is a little like going off-roading. For an ovarian cancer patient, an off-label drug is one that has been indicated or approved by the FDA, and shown effective for a type of cancer, but not ovarian cancer. For example, the drug pemetrexed (ALIMTAŽ) has been approved to treat certain specific types of lung cancer. Some physicians and scientists think that pemetrexed might also be effective in other cancers, including ovarian because of its action on a basic cell function.
Patients who choose an off-label option are embarking on a treatment course that has not been well established because the well-traveled drug routes have not been effective. This is the time that the patient and treatment team may decide to go off-roading by exploring other treatment options.
Nearly all patients that come to Clearity have already had their cancers recur after one or more of the established treatment options have failed and many of these patients have started to look at clinical trials or off-label treatment options. Although less established, these options are not completely uncharted and several guides can help patients navigate which might be the best path to explore.
A patient's own molecular profile can act as an orienting compass to aid decision-making. When a patient has her tumor profiled and analyzed through Clearity, she learns, which drugs her tumor is most likely to respond to and which it is most likely to resist. Clearity compares each patient's tumor profile to a broad range of scientific information and interprets the individual patient test results in comparison to other ovarian cancer patient profiles that are stored in our privacy-protected
Diane Barton Database
.
For example, if a patient's profile shows low levels of thymidylate synthase (TS), an enzyme that helps make DNA, this is a good sign that the off-label use of pemetrexed may be a good option for her.
Pemetrexed acts by impersonating an important building block of DNA called folate; which is why this drug is called an anti-folate. The anti-folate interacts with the cellular reproduction machinery much the same way that natural folates do, but rather than moving through the machinery to make DNA and other important cellular components, the anti-folate gums up the gears. TS is one of these gears.
Normally, TS performs an important step in the production of DNA. Rapidly dividing cells such as cancer cells need to make more DNA to pass along to their daughter cells.
But when pemetrexed interferes with this rapid DNA production, cancer cells can suffer serious damage and death. Studies of other types of tumors, including colon and lung, suggest that if tumor cells have lots of TS present, then anti-folates such as pemetrexed are not effective. That's because having extra TS around may help cells get around the gummed-up machinery. If it's true in those cancers, it may also be true in ovarian.
Christy is a Clearity patient who is familiar with off-roading on pemetrexed. She was diagnosed with ovarian cancer in 2002 and has been through several combinations of chemotherapy as her cancer became controlled and then recurred. In 2008, on the basis of comparing her genetic profile with the Clearity database, she and her oncologists decided to try pemetrexed and since then, she has received 8 courses of treatment. Her disease has been stable for many months.
Using a drug off-label still carries a degree of uncertainty. Just because it's been proven in one cancer is no guarantee it will work in ovarian cancer. The goal is not to make treatment choices randomly and blindly, but to choose one that makes scientific sense. For ovarian patients with low TS levels, choosing to take pemetrexed off-label may be a good off-road path.
- Cory Bentley, PhD
