Anticancer agent – farletuzumab
Ovarian cancer has often reached an advanced stage by the time it is diagnosed
Ovarian cancer is difficult to treat, as recurrence is common when it is advanced, and the cancer has often reached an advanced stage by the time it is diagnosed. One potential target is human folate receptor alpha, which has limited distribution in normal tissue but is highly expressed in some tumours, including recurrent and metastatic ovarian tumours. Eisai subsidiary Morphotek has created a humanised monoclonal antibody with a high affinity for FR-a,1 which is now in clinical trials in patients with ovarian cancer.
In a Phase I dose escalation study designed to determine safety and find the maximum tolerated dose, 25 heavily pretreated patients with epithelial ovarian cancer that was refractory or resistant to platinum therapy were given 12.5–400mg/m2 on days 1, 8, 15 and 22 of a five-week cycle.2 No dose limiting toxicities or maximum tolerated dose were seen, and dose escalation was continued to 400mg/m2. Tumour targeting was confirmed using nuclear imaging. There were no objective responses, but nine patients achieved stable disease, with three patients receiving continued therapy up to three cycles.
A Phase II trial has also been carried out.3 Here, 54 subjects with platinum-sensitive epithelial ovarian cancer in the first relapse were given weekly doses of the antibody either as a single agent or in combination with carboplatin and taxane for six cycles, followed by farletuzumab maintenance. Of these, 28 subjects with asymptomatic relapse were given the antibody as a single agent, and 21 moved on to the combination arm after having the single agent therapy; the remaining 26 patients were started immediately on combination.
It was well tolerated both as a single agent, and gave no additive toxicity to carboplatin and taxane. The duration of each subject’s second response was compared with the duration of their own first response. In nine of 44 evaluable subjects, the second remission was at least as long as the first; it thus appears to increase significantly the objective response rate compared with carboplatin/taxane alone in platinum-sensitive first relapsed ovarian cancer patients. Trials are continuing.
reference
1. W. Ebel et al. Cancer Immun. 2007, 7, 6
2. J.A. Konner, Clin. Cancer Res. 2010, 16, 5288
3. A.J. White et al. J. Clin. Oncol. 28 (15, Suppl.), Abst. 5001