Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial.

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status

Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial.

PURPOSE: Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. RESULTS: Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. CONCLUSION: Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

Poor outcome of elderly patients with platinum-sensitive recurrent ovarian cancer: results from the SOCRATES retrospective study.

BACKGROUND: Elderly patients with ovarian carcinoma have a poorer prognosis compared with their younger counterpart, and this depends in most cases on undertreatment. The aim of this study was to evaluate, retrospectively, the pattern of care and the prognosis of elderly patients with platinum-sensitive recurrent ovarian cancer. The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. PATIENTS AND METHODS: Patients with recurrent ovarian cancer with >6 months of platinum free interval were considered eligible. Four-hundred-ninety-three patient files were collected and 425 were considered eligible and analyzed. Ninety-four patients with age >or=70 years and 331 patients with age <70 years were analyzed. RESULTS: Recurrence free interval (RFI), PS, and number of disease sites were similar among the two groups. A lower proportion of elderly patients underwent secondary cytoreduction (8.9% compared to 23.9%; p=0.0018). The mean number of chemotherapy lines received for recurrence was 2.7 and 2.5 in young and aged patients, respectively. Elderly patients received more frequently at second line single agent platinum than platinum-combination therapy or other non-platinum chemotherapy. The response rate to the second line chemotherapy was higher in younger patients than in the elderly population (CR+PR, younger: 67.2%; elderly: 46.5%; p=0.0004). Median overall survival from recurrence was 30.7 months in the younger patients and 23.6 months in the elderly group (p=0.0037). At multivariate analysis, number of disease sites (>1 vs. 1), performance status at recurrence (2-3 vs. 0-1), RFI (6-12 months vs. >12 months), age at recurrence, were independently associated with survival. CONCLUSION: Elderly patients with platinum-sensitive recurrent ovarian cancer receive less surgery and chemotherapy. Response to chemotherapy is better in younger patients. Age is an unfavourable factor independently associated to a worst prognosis.