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Select Excerpts from the Interview
Track 1
DR LOVE: What important data sets in ovarian cancer were presented at
ASCO this year?
DR THIGPEN: The most interesting abstract was the Japanese study evaluating
weekly paclitaxel with every three-week carboplatin versus every
three-week carboplatin/paclitaxel in women with advanced ovarian cancer
(Isonishi 2008). The response rate was essentially equivalent — approximately
55 percent — for both arms, but the median progression-free survival was 28 months versus 17 months in the weekly and every three-week arms, respectively,
which is a dramatic difference. There were not enough events for a
final survival analysis, but two-year survival was 83 percent with weekly paclitaxel
and 77 percent with the every three-week regimen, which was statistically
significant.
These data fly in the face of data reported six years ago from a study that evaluated weekly versus every three-week single-agent paclitaxel as second-line therapy, which revealed no difference between the two schedules (Rosenberg 2002). However, the Japanese data do correspond with the observations in breast cancer that weekly paclitaxel may be the most effective schedule (Sparano 2008).
The Japanese study needs to be repeated before we can routinely introduce the regimen into clinical practice, and the Gynecologic Oncology Group is planning on conducting that study in the near future.
Tracks 3-4
DR LOVE: What are your thoughts about intraperitoneal (IP) therapy for
ovarian cancer?
DR THIGPEN: This is a controversial topic. In January 2006, the National
Cancer Institute declared a combination of IP therapy and intravenous (IV)
therapy to be the standard treatment for small-volume residual advanced ovarian
cancer. However, they couldn’t recommend a specific regimen (NCI 2006).
At our institution, IP therapy remains an experimental technique that is generally not used outside of a clinical trial for several reasons. First, it’s quite toxic and many patients are unable to tolerate it. In the last GOG study of IP therapy, 48 percent of the patients received three or fewer cycles of IP therapy and only 42 percent were able to complete six cycles (Armstrong 2006).
Second, we are not certain whether the addition of IP therapy is superior to IV carboplatin/paclitaxel. In all of the Phase III studies of IP therapy conducted in the United States to date, the control arm has been an IV cisplatin-based regimen. Yet evidence from the last GOG study comparing IV cisplatin/paclitaxel to IV carboplatin/paclitaxel showed that the latter might be superior (Ozols 2003).
To address this question, GOG is planning to begin a trial in the next six to 12 months comparing a control arm of IV carboplatin/paclitaxel to two IP regimens. One IP regimen will utilize cisplatin and the other carboplatin.
Track 7
DR LOVE: What studies have been conducted with bevacizumab for the
treatment of advanced ovarian cancer?
DR THIGPEN: The initial Phase II study, GOG-0170D, evaluated bevacizumab at 15 mg/kg every three weeks in patients who had received one or
two prior chemotherapy regimens. The trial reported an objective response
rate of 21 percent, a complete response rate of three percent and progression-free
survival of at least six months in 40 percent (Burger 2007; [3.1, page 12]).
Two other Phase II studies evaluated bevacizumab in patients with more heavily pretreated disease. Among those patients who had received as many as three to five prior regimens, an increase in the complication rate was observed, specifically bowel complications (Cannistra 2007; Monk 2006). This suggests that if we use bevacizumab in ovarian cancer, it ought to be in the front-line setting or at first relapse.
DR LOVE: What about bevacizumab combined with chemotherapy?
DR THIGPEN: A trial evaluating cyclophosphamide with bevacizumab showed
activity, but it was not a randomized study so we don’t know whether the
combination was better (Garcia 2008; [1.1]). Most of us feel strongly that
administering bevacizumab with chemotherapy will be a better approach
because of the possibility that it will improve the delivery of chemotherapy to
the tumor by stabilizing the vasculature.
Tracks 8-10
DR LOVE: For patients with recurrent ovarian cancer, how do you define
and approach platinum-sensitive versus platinum-resistant disease?
DR THIGPEN: Chemosensitive disease is defined as that which responded to
the previous treatment and did not progress for at least six months. Patients
with chemosensitive disease should be treated with a regimen that is the same
or similar to the initial one because their chances of responding are good.
Disease that does not meet those criteria should be labeled as chemoresistant and should be treated with alternative drugs. For practical purposes, we talk about platinum-resistant or platinum-sensitive disease because all patients initially receive a platinum-based regimen. So patients who initially received paclitaxel/carboplatin and experience relapse more than six months later will fare better with a platinum-based regimen more so than anything else.
DR LOVE: How do you treat platinum-resistant, recurrent ovarian cancer?
DR THIGPEN: I prefer single agents in this setting because we don’t have any
proof that combinations are better. The six drugs that are commercially available,
reimbursable and clearly have activity in platinum-resistant disease are
pegylated liposomal doxorubicin (PLD), topotecan, gemcitabine, oral etoposide,
weekly paclitaxel (if the patient received every three-week paclitaxel up
front) and docetaxel.
All of these agents have response rates in the range of 15 to 20 percent and offer some survival benefit in the second-line setting. I generally start with PLD because it’s administered once every four weeks, which is convenient for our patients. I use topotecan second, gemcitabine third, etoposide fourth, weekly paclitaxel fifth, and docetaxel sixth. Most of our patients will receive five or six different regimens.
There are two other agents that we should consider adding to that list — pemetrexed and bevacizumab. Bevacizumab, however, still has a question mark because of the increased complication rate among patients who have received multiple prior treatments.
| Table of Contents | Top of Page |
EDITOR
Neil Love, MD
INTERVIEWS
Tate Thigpen, MD
- Select publications
Ursula A Matulonis, MD
- Select publications
Robert A Burger, MD
- Select publications
Bradley J Monk, MD
- Select publications
Ovarian Cancer Update:
A CME Audio Series and Activity
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