Platinum-based chemotherapy (PBC) should be not be delayed in favor of non-platinum-based chemotherapy (NPBC) in patients with partially platinum-sensitive ovarian cancer, a new study shows.

The study, “Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study,” was published in the Journal of Clinical Oncology.

Ovarian cancer tends to progress despite surgery and PBC, the latter being the first-line chemotherapy offered to patients.

Upon progression, patients can be re-treated with PBC, but the effectiveness of treating again with PBC is increased if the period of time since initial PBC is longer. So, if recurrence comes within six months of the first PBC treatment (platinum resistant), patients are treated with NPBC; and, if patients progress after 12 months of the first PBC (platinum sensitive), they are treated with PBC. There is, however, uncertainty on what to do when a patient progresses between six and 12 months (partially platinum-sensitive).

In 1999, it was hypothesized that NPBC could be a means of increasing the time since first PBC and enhancing the sensitivity to PBC re-treatment in partially platinum-sensitive patients.

However, in 2006, a study conducted by the Multicenter Italian Trials in Ovarian Cancer (MITO) group suggested that NPBC after initial PBC treatment may not be the best choice.

In 2008, researchers launched MITO-8 (NCT00657878), a Phase 3 trial evaluating whether prolonging the PFI (platimum-free interval) by conducting a NPBC actually would improve the outcome of patients with partially platinum-sensitive ovarian cancer.

Researchers recruited 215 patients with ovarian cancer that experienced disease progression between six and 12 months after the last PBC and then were assigned at a 1:1 ratio to either receive NPBC followed by PBC at subsequent relapse (the experimental arm), or the standard sequence, which involves receiving PBC at current relapse followed by NPBC at the subsequent relapse.

Results from the trial indicated there was no overall survival benefit for patients in the experimental arms compared to patients in the standard arm; the median overall survival was 21.8 months vs. 24.5 months, respectively.

In fact, progression-free survival actually was significantly shorter in the experimental arm at a median of 12.8 months versus in the standard arm, which was 16.4 months. Patients in the experimental arms were 1.41-fold more likely to experience a shorter progression-free survival.

Also, the global quality-of-life change was worse after three cycles in the experimental arm compared to the standard arm.

There were some benefits in the experimental arm with regard to adverse events, as more patients in the standard arm experienced any-grade neutropenia (69.5% vs. 55.1%), musculoskeletal symptoms (3.8% vs. 0%), neuropathy (50.5% vs. 33.6%), and severe nausea (3.8% vs. 0%).

The authors concluded: “MITO-8 strongly supports the recommendation that platinum rechallenge not be delayed in favor of a nonplatinum treatment in patients with partially platinum-sensitive OC. It is also advisable that PBC be used as the control arm in future trials of new drugs in this setting.”