Last Modified: May 8, 2009
Dear OncoLink "Ask The Experts,"
I have Stage IIIC ovarian cancer, had optimal debulking and then 9 rounds of IV/IP carbo/Taxol, the first three of which were all IV due to port problems. The oncologist is asking me to consider 24 weekly IV treatments of Taxol, which is said to have few side effects and may increase the disease-free interval. What is your opinion of this? I know it is controversial, but increasing disease-free interval seems valuable to me, and I am wondering if it may increase overall survival.
Christina S. Chu, MD, Assistant Professor of the Division of Gynecologic Oncology at the University of Pennsylvania Health System, responds:
In the large Gynecologic Oncology Group phase III trial of 3 months vs. 12 months of Taxol given every 4 weeks, patients randomized to the 12 month arm experienced a 7 month improvement in time to relapse. However, because the trial met the stopping rules at the interim analysis, the study was terminated early, so no conclusion regarding effect of consolidation therapy on overall survival can be made. The results of this trial remain controversial for this very reason. Patients in the 12 month arm also experienced significantly more side effects, peripheral neuropathy in particular, and on average only tolerated 9 months of therapy before discontinuing treatment altogether. Stated another way, it is unclear if patients who undergo 12 months of consolidation actually derive an overall survival benefit, but they certainly do incur greater side effects at a time when they only have occult disease, and would otherwise be feeling well. If there is truly no survival benefit to consolidation, it may be that those patients who receive treatment at the time of an actual documented recurrence may still respond as well to chemotherapy as those who receive treatment when the disease is occult. Because of these results, the use of consolidation therapy remains a good option, though it cannot yet be considered standard of care.
At this point, the Gynecologic Oncology Group's current randomized phase III consolidation trial for patients achieving complete remission after initial surgery and chemotherapy consists of 3 arms: 1) routine follow up with observation with periodic CA125 and physical exam, 2) monthly Taxol for 12 months, or 3) monthly Xyotax for 12 months. Xyotax links paclitaxel to a polyglutamate polymer, and has been shown to become preferentially trapped in tumor blood vessels allowing localization of the chemotherapeutic moiety in the tumor. Monthly Xyotax may also be an option for consolidation.
There are a few studies using weekly Taxol for this purpose as well. The therapy seems to be well tolerated, but there is yet to be any proven benefit in overall survival, though the therapy may give similar benefits in time it takes for disease to recur.