Randomized Phase II Trial of Carboplatin and Paclitaxel with or without Lonafarnib in First-Line Treatment of Epithelial Ovarian Cancer Stage IIB-IV

Randomized Phase II Trial of Carboplatin and Paclitaxel with or without Lonafarnib in First-Line Treatment of Epithelial Ovarian Cancer Stage IIB-IV: Publication year: 2012

Source: Gynecologic Oncology


Objectives This study evaluates whether a molecular targeted therapy with the farnesyl transferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).

Patients and Methods We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175mg/m2) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.

Results 105 patients were recruited( 53 patients were randomised to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm:.....

Conclusion The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.