For many years I have been interested in the ovarian cancer literature.
After all, it was our group that originally developed the platinum plus gemcitabine doublet (two drug combo) and tested it through a Phase II trial conducted by the Gynecologic Oncology Group (GOG). The study’s results were reported in Gynecologic Oncology in 2006.
I then watched with interest as the GOG 182 five-arm clinical trial unfolded.
This international study of over 4,000 patients randomly mixed and matched drug combinations but provided no evidence of superiority of one arm over another.
The final conclusion of the manuscript that reported these results (Bookman, MA., Brady, MF, McGuire, WP, et al. J Clin Oncol 27: 1419-1425, 2009), stipulated that carboplatin plus taxol remained the “gold standard” for advanced epithelial ovarian carcinoma.
A study of over 900 patients that compared carboplatin plus gemcitabine to carboplatin plus paclitaxel induction (Gordon A, Teneriello M, Lim, P, et al Clinical Ovarian Cancer, 2, 2:99-105, 2009) again provided comparable outcomes between arms yet carboplatin plus taxol remains the “gold standard.”
To this collection of published experiences, we now add the report by Sandro Pignata and co-investigators from the MITO-2 Phase III trial (Pignata, S., Scambia, G., Ferrandina, G., et al. J Clin Oncol 29: 3628-3635, 2011).
This clinical trial conducted by Italian investigators compared carboplatin plus taxol to carboplatin plus pegylated liposomal doxorubicin (PLD) known in the U.S. as Doxil. Four hundred and ten patients were randomized to each arm of the trial.
The results revealed numerical superiority for the carboplatin plus PLD arm in terms of median progression-free survival (19 months vs. 16.8 months) and numerical superiority for overall survival for the carboplatin plus PLD over the carboplatin plus taxol arm (61.6 vs. 53.2 months).
However, these results did not achieve statistical significance.
Therefore, the authors conclude that carboplatin plus taxol “remains the standard first-line chemotherapy for ovarian cancer.” While they do grant that, based on toxicity, carboplatin plus PLD could be considered as an alternative therapy.
Questions to Ponder
With the GOG 182 study, the Gordon study (comparing carboplatin plus gemcitabine) and the most recent Pignata study comparing carboplatin plus PLD all establishing activity for several first-line regimens, why is it that the gynecologic oncologists continually return to carboplatin plus taxol as the “gold standard?”
Is there not ample evidence that several regimens provide similar results and survivals? Is there not evidence that the toxicities differ?
Why can’t the gynecologic oncologists get off the dime?
Why can’t they admit that several treatment regimens are appropriate and indicated for the malignancy? Why can’t they admit that some patients may, in fact, do better with one treatment over another?
And, finally, why can’t they admit that using laboratory analyses to determine a patient's functional profile has the potential to select amongst these regimes to provide the best outcomes for the majority of patients?
As always, I appreciate your thoughts and comments.