Tolerability of PLD/oxaliplatin regimen in recurrent ovarian cancer patients with previous fragility to carboplatin/paclitaxel treatment.

OBJECTIVES: This retrospective analysis aims at describing the safety profile of treatment with pegylated liposomal doxorubicin (PLD) and oxaliplatin in recurrent ovarian cancer patients who experienced myelotoxicity (principally neutropenia) during first line chemotherapy with carboplatin and paclitaxel. METHODS: We reviewed the medical records of patients with relapsed ovarian cancer treated with PLD/Oxaliplatin at the Istituto Oncologico Veneto (IOV)/IRCCS, Padua University between 2002 and 2008. RESULTS: A cohort of 16 patients who developed myelodepression and other toxicities of grade 3 to grade 4 during first line chemotherapy with carboplatin/paclitaxel, were selected for this retrospective study. Patients had developed predominantly grade 3 to grade 4 neutropenia and grade 1 to grade 3 thrombocytopenia as major toxicities during primary chemotherapy with carboplatin and paclitaxel. Following relapse or disease progression, PLD/oxaliplatin chemotherapy was administered at 30 to 35 and 70 mg/m(2), respectively, over 2 day, every 4 weeks. CONCLUSIONS: Complete regression and stabilization of bone marrow suppression and no allergic reactions were seen with PLD/oxaliplatin treatment. The estimated median overall survival was 51.2 months. PLD/oxaliplatin chemotherapy did not show hematological toxicity and was feasible and active in this group of pretreated frail patients.

Positive experience of intraperitoneal chemotherapy followed by intravenous chemotherapy in heavily pretreated patients with suboptimal residual ovarian cancer and primary peritoneal cancer.

AIMS AND BACKGROUND: To assess feasibility and toxicity of intraperitoneal administration of cisplatin and paclitaxel, followed by intravenous chemotherapy in pretreated patients with suboptimal ovarian cancer (residuum >1 cm) or primary peritoneal tumor, and suffering from ascites and/or intestinal obstruction. METHODS: Fourteen relapsed ovarian cancer patients, 5 of whom were platinum sensitive (platinum-free interval >6 mo), 7 platinum-resistant (platinum-free interval <6 mo), and 2 platinum-refractory, received one cycle of intraperitoneal cisplatin, 100 mg/m2 on day 1, and two cycles of intraperitoneal paclitaxel, 120 mg/m2 on days 8 and 14. Intravenous chemotherapy was administrated 4 weeks following the last intraperitoneal paclitaxel instillation. Blood and peritoneal fluid samples were harvested at 0, 1, 4 and 24 h after ending paclitaxel delivery to guarantee proper tumor exposure and patient safety. RESULTS: Intraperitoneal cisplatin determined 6 cases of vomiting grade 1-2 (40% of the morbidity). Intraperitoneal paclitaxel was associated with 6 events of grade 1-2 abdominal pain; the only grade 4 toxicity was one case of neutropenia and one of mucositis. Ascites decreased in 11 patients: the median time to first need for paracentesis was 5 months, compared to a median baseline paracentesis of 4 weeks. Three intestinal normalizations were obtained. The median overall survival was 10 months for our cohort of patients. Intraperitoneal paclitaxel clearance was significantly higher in patients with suboptimal tumor and symptomatic disease than in patients with smaller residual masses and without ascites (P = 0.004). CONCLUSIONS: Intraperitoneal treatment was feasible, and enhanced response to the following intravenous chemotherapy was seen in these patients.

Family history of cancer rather than p53 status predicts efficacy of pegylated liposomal doxorubicin and oxaliplatin in relapsed ovarian cancer.

BACKGROUND: The aim of the study was to assess the efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin in patients affected by relapsed epithelial ovarian cancer with a family history of BRCA and p53 mutations. METHODS: Seventy-two women received a median of 7.5 courses of PLD at 30 to 35 mg/m2 plus oxaliplatin at 70 mg/m2, and associations between BRCA1/2 and TP53 status and overall survival (OS) were determined. Thirty-eight had a short platinum-free interval (PFI; <12 months), and 34 had a long PFI (> or =12 months). RESULTS: Nine patients had BRCA1 mutations, and 1 had a BRCA2 mutation. Platinum sensitivity was associated with OS (P = 0.0001). At a median follow-up of 9.3 months, objective response rate, median time to progression, and OS were 47.3%, 5.8 months, and 12.9 months, respectively, in short PFI compared with the 76.5%, 11.5 months, and 47.7 months in long PFI. p53 status did not correlate to these parameters. The median time to progression was 11.5 months for high-risk patients versus 6.5 months for patients with sporadic cancer (P = 0.0188), and the median OS from the start of treatment was 48.7 and 16.2 months (P = 0.0032), respectively. Toxicity was mostly grade 1 or 2. CONCLUSIONS: High response rates in the long-PFI patients indicate that this treatment is beneficial and well tolerated. Platinum sensitivity and positive family history and/or a BRCA1/BRCA2 mutation are a useful predictor of response.