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In a review of adjuvant therapy for high-risk adenocarcinoma of the uterus, presenters included highlights of the previously reported Postoperative Radiation Therapy for Endometrial Carcinoma (PORTEC)-1 trial (Lancet 2000; 355:1404) and the Gynecologic Oncology Group (GOG) 99 trial (Gynecol Oncol 2004; 92:744). In both randomized studies, investigators compared postoperative pelvic radiotherapy with observation and showed that radiotherapy decreased the likelihood of pelvic recurrences but did not affect survival. To update these results, presenters described the results of the multicenter, phase III PORTEC-2 trial, in which postoperative external beam radiotherapy (EBRT) was compared with vaginal brachytherapy (VBT) in women with high-risk or intermediate-risk endometrial cancer (J Clin Oncol 2008; 26:suppl:abstract LBA5503). Results showed that 3-year actuarial rates of vaginal relapse were lower, but not significantly so, in the VBT arm than in the EBRT arm. Pelvic recurrence rates were also lower in the VBT arm than in the EBRT arm (0.7% vs. 3.6%; P=0.03). Three-year rates of vaginal, pelvic, and distant relapse as first failure were 0%, 1.3%, and 6.4%, respectively, in the VBT arm and 1.6%, 0.7%, and 6.0% in the EBRT arm. Three-year overall survival did not differ between the two study arms. Given the similar rates of distant metastases, overall survival, and relapse-free survival, and the improved quality of life after VBT versus EBRT, the authors concluded that VBT should be the preferred treatment for patients with high-risk endometrial cancer. PORTEC-3 trial investigators currently are enrolling patients with high-risk, early-stage endometrial cancer for randomization to either pelvic RT alone or pelvic RT with concurrent cisplatin followed by carboplatin and paclitaxel.
Investigators reported the results of a phase III trial of four cisplatin-containing doublet combinations in stage IVB recurrent or persistent cervical cancer (J Clin Oncol 2008; 26:suppl:abstract LBA5504). The trial involved 513 patients randomized to cisplatin plus paclitaxel, cisplatin plus topotecan (Hycamtin), cisplatin plus vinorelbine, or cisplatin plus gemcitabine. The three experimental combinations demonstrated no significant survival benefit over cisplatin and paclitaxel. Other current trials in this patient population include GOG 76DD, a study examining the efficacy of cisplatin plus cetuximab (Erbitux).
Novel therapies for the management of ovarian cancer were reviewed by several investigators. One group evaluated AZD2281, a PARP (poly ADP-ribose polymerase) inhibitor with single-agent activity in ovarian cancer patients without BRCA mutations (J Clin Oncol 2008; 26:suppl:abstract 5510). Of 32 evaluable patients, 14 achieved partial response; 13 met Gynecologic Cancer Intergroup (GCIG) CA125 criteria, and 10 met Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The authors concluded that AZD2281 was well tolerated and demonstrated compelling activity in patients with BRCA mutations.
Another group described an exploratory phase II study of MORAb-003, a monoclonal antibody for folate receptor alpha, in patients with platinum-sensitive ovarian cancer in first relapse (J Clin Oncol 2008; 26:suppl:abstract 5500). MORAb-003 plus platinum and taxane was associated with significantly higher overall response rate (compared with historic data for platinum and taxane alone) and with longer duration of the second remission compared with the first remission.
Other investigators described the activity of cediranib (Recentin), an oral tyrosine kinase inhibitor, in recurrent epithelial ovarian cancer (J Clin Oncol 2008; 26:suppl:abstract 5501). Cediranib was active against both platinum-resistant and platinum-sensitive ovarian cancer (overall response rate, 31%) and is being tested in ICON6, a phase III trial designed to evaluate platinum-based chemotherapy alone or in combination with cediranib. The ICON6 investigators are also assessing cediranib in terms of overall survival, progression-free survival, and quality of life in women with platinum-sensitive relapsed ovarian cancer who are receiving maintenance cediranib therapy compared with no maintenance therapy.