Randomized phase III study comparing paclicalcarboplatin with paclitaxelcarboplatin in patients with recurrent platinumsensitive epithelial ovarian cancer

Background: Paclical (Pcal), a CremophorELfree formulation of paclitaxel (Oasmia Pharmaceutical AB) was compared with Paclitaxel (Pxel). Pcal can be administered without antiallergic premedication as an iv infusion over 1 hour. Methods: Primary objective: To show noninferiority between Pcal and Pxel in PFS using CT scans (RECIST) in platinsensitive recurrent ovarian, fallopian tube or peritoneal carcinoma. To obtain 379 events of progression 850 were estimated to be accrued (noninferiority HR = 1.2; α = 0.25 (onesided) ; β = 0.8). Patients were randomized to Pcal 250 mg/m2 iv 1 hr or Pxel 175 mg/m2 iv 3 hrs, both followed by Carboplatin, AUC 56, q 3 wks. Stratification factors: CA 125 value ( < 250 U/L or 250 U/L) and relapse (1st or 2nd). CT scans were done before treatment, after 3 and 6 cycles and at the time of clinical symptoms or CA125 progression. A subset of 243 patients had CTs done every 3rd month until progression. Main inclusion criteria: response to prior platin containing treatment, > 6 months platinfree interval (PFI), and CA 125 > 2 x UNL. Patients with a history of severe allergy to study drugs were excluded. Results: 789 patients were 1:1 randomized in the period 2009 to 2012 in 81 centers. Inclusion was stopped when 437 patients showed progression. Main baseline characteristics were similar (PFI 612 months: 40% vs 43 %, > 12 months 58% vs 57%; second line: 76% vs 76% for Pcal and Pxel, respectively). Noninferiority of PFS for Pcal (10.3 months) compared to Pxel (10.1 months) was observed (HR:0.86 CI:0.72-1.03 p = 0.0938). In the subgroup of patients with CTs performed every 3rd month during followup the PFS was 12.2 versus 10.2 months, respectively (HR:0.76 CI:0.56-1.03 p = 0.0798). Response according to RECIST: 67% vs 65%; according to GCIG CA125 criteria: 86% vs 85%, respectively. AEs were noted in 90% in the Pcal group and 87% in the Pxel group. All grade peripheral neuropathy were 29% vs 32% and myalgia 11% vs 13%, respectively (NS). Severe allergic reactions were seen in 2% vs 1%. Conclusions: Pcaltreatment is as effective and safe as Pxel, without standard use of premedication and a shorter infusion time.