The overall response rate was 54% with a median survival of 22.5 months. When evaluated according to platinum sensitivity, there was

a response rate of 66.7% among the 29 platinum-sensitive patients and of 28.6% in the 14 platinum-resistant patients. There were 5 (12%) grade 3 or 4 toxicities and only 3 patients (7%) required dose reduction. Neutropenia was the treatment limiting toxicity. Some phase II studies explored Inhibitors,research,lifescience,medical the efficacy of PLD associated with topotecan (TPT) [43], as well as paclitaxel (PTX) [44], vinorelbine (VNR) [45], and ifosfamide (IFO) [46]. Overall, response rates of about 28% to 37% with a median PFS of 5.5 to 7.5 months were found, figures Inhibitors,research,lifescience,medical which are quite comparable to those reported with other nonplatinum combinations. The association with weekly paclitaxel was well selleck products tolerated, as was the PLD/VNR combination [45]. In contrast, PLD/TPT, even if tested at different doses of the two drugs, was characterized by an unacceptable rate of severe anemia (48%), leukopenia (70%), and thrombocytopenia (44%) [43]. 3.2. PLD Single-Agent Phase III Randomized Trials Table 2 summarizes the results from randomized

trials using PLD alone or in combination in phase III studies [47–52]. Table 2 Phase-III studies with pegylated Inhibitors,research,lifescience,medical liposomal doxorubicin (PLD) as a single agent or in combination regimens. In the first trial [48], Gordon randomized 474 ovarian cancer patients at first recurrence (stratified by PFI) to PLD (50mg/m2 every 4 weeks) or topotecan (1.5mg/m2/day for 5 consecutive days every 3 weeks). In platinum-resistant Inhibitors,research,lifescience,medical disease (n = 255) no significant difference was seen in response rate, PFS, or OS between the two treatment arms, while in platinum-sensitive patients (n = 219), median PFS and OS were significantly prolonged in PLD-treated Inhibitors,research,lifescience,medical patients compared to TPT-treated patients (P value = 0.037 and P value = 0.008, resp.). More mature survival selleck 17-AAG analysis confirmed the long-term advantage for platinum-sensitive patients receiving PLD versus TPT (median OS = 27 months versus

17.5 months, hazard ratio (HR) = 1.432, P value = 0.017) [49]. Moreover, for partially platinum-sensitive disease (n = 122), the HR favored PLD versus TPT (HR = 1.58, P value = 0.021). About the tolerability profile, grade 3/4 haematological toxicity occurred more frequently Drug_discovery and more severely in TPT compared to PLD; in particular, severe neutropenia was documented in 77% of TPT–treated patients versus 12% of PLD-treated patients (P < 0.001), and thrombocytopenia was found in 34% of TPT versus 1% of PLD cases (P < 0.001). No case of severe HFS was documented in the TPT arm while it was registered in 23% of PLD-treated patients (P < 0.001) with no difference in quality of life perceived by the patient. In a second randomized trial conducted by O’Byrne et al.