ABSTRACT
BACKGROUND: BK-UM (CRM197) is a mutant form of diphtheria toxin and a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF). We assessed the safety, pharmacokinetics, recommended dose, and efficacy of BK-UM in patients with recurrent ovarian cancer (OC) or peritoneal cancer (PC), and measured HB-EGF levels in serum and abdominal fluid after BK-UM administration. METHODS: Eleven patients with advanced or recurrent OC or PC were enrolled and treated with BK-UM via the intraperitoneal route. The dose was escalated (1.0, 2.0, 3.3, and 5.0 mg/m2) using a 3 + 3 design. RESULTS: Eight of 11 patients completed treatment. No dose-limiting toxicity (DLT) was experienced at dose levels 1 (1.0 mg/m2) and 2 (2.0 mg/m2). Grade 3 transient hypotension as an adverse event (defined as a DLT in the present study) was observed in two of four patients at dose level 3 (3.3 mg/m2). Treatment with BK-UM was associated with decreases in HB-EGF levels in serum and abdominal fluid in seven of 11 patients and five of eight patients, respectively. Clinical outcomes included a partial response in one patient, stable disease in five patients, and progressive disease in five patients. CONCLUSIONS: BK-UM was well tolerated at doses of 1.0 and 2.0 mg/m2, with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m2 BK-UM is recommended for subsequent clinical trials. TRIAL REGISTRATION: This trial was prospectively performed as an investigator-initiated clinical trial. The trial numbers are UMIN000001002 and UMIN000001001, with registration dates of 1/30/2008 and 2/4/2008, respectively. UMIN000001001 was registered as a trial for the continuous administration of BK-UM after UMIN000001002 .
Subject(s)
Bacterial Proteins/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Aged , Bacterial Proteins/pharmacokinetics , Dose-Response Relationship, Drug , Female , Heparin-binding EGF-like Growth Factor/metabolism , Humans , Middle Aged , Neoplasm Recurrence, Local/metabolism , Ovarian Neoplasms/metabolism , Peritoneal Neoplasms/metabolismABSTRACT
OBJECTIVE: This study aimed to evaluate the efficacy of paclitaxel and carboplatin in patients with completely or optimally resected uterine carcinosarcoma. MATERIALS AND METHODS: We conducted a single-arm multicenter prospective phase II trial at 20 Japanese medical facilities. Eligible patients had histologically confirmed uterine carcinosarcoma without prior chemotherapy or radiotherapy. Patients received 6 courses of 175 mg/m (2)paclitaxel over 3 hours, followed by a 30-minute intravenous administration of carboplatin at an area under the serum concentration-time curve of 6. RESULTS: A total of 51 patients were enrolled in this study, 48 of whom underwent complete resection and 3 of whom underwent optimal resection. At 2 years, the progression-free survival and overall survival rates were 78.2% (95% confidence interval [CI], 64.1%-87.3%) and 87.9% (95% CI, 75.1%-94.4%), respectively. At 4 years, these rates were 67.9% (95% CI, 53.0%-79.0%) and 76.0% (95% CI, 60.5%-86.1%), respectively. Although 15 patients showed disease recurrence during the follow-up period (median, 47.8 months; range, 2.1-72.8 months), a total of 40 (78.4%) patients completed the 6 courses of treatment that had been planned. CONCLUSIONS: The combination of paclitaxel and carboplatin was a feasible and effective postoperative adjuvant therapy for patients with completely or optimally resected uterine carcinosarcoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinosarcoma/drug therapy , Uterine Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinosarcoma/mortality , Carcinosarcoma/pathology , Carcinosarcoma/surgery , Combined Modality Therapy , Feasibility Studies , Female , Follow-Up Studies , Humans , Hysterectomy , Lymph Node Excision , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Prognosis , Prospective Studies , Survival Rate , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology , Uterine Neoplasms/surgeryABSTRACT
BACKGROUND: Endometrial cancer (EC) has a poor prognosis due to drug resistance. PATIENTS AND METHODS: We evaluated the safety and efficacy of adjuvant combination chemotherapy with docetaxel plus cisplatin ((DP) docetaxel, 70 mg/m(2); cisplatin, 60 mg/m(2); every 28 days) in EC patients at intermediate-risk (IR) or high-risk (HR) for recurrence. RESULTS: Sixty-four patients diagnosed with EC were enrolled. Stage-I, -II, -III and -IV disease was noted in 23, 7, 28 and 6 patients, respectively. Histopathological analyses revealed that 56, 3, 1 and 4 patients had endometrioid, serous, clear-cell or "other" types of carcinoma. Grade-3/4 hematologic toxicities were found at 80% and 95% in patients in IR and HR groups, respectively. In IR and HR groups, mean progression-free (PFS) survival was 69.5 and 29.5, while overall survival (OS) was 59.6 and 47.5 months, respectively. CONCLUSION: DP may be clinically safe and useful treatment for EC.