A phase II study of two topotecan regimens evaluated in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer: a Gynecologic Oncology Group Study (GOG 146Q).

OBJECTIVE: To evaluate the efficacy and safety of topotecan in patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinomas. METHODS: A randomized phase II analysis of platinum-sensitive patients with measurable disease was performed independently assessing intravenous topotecan 1.25 mg/m2 daily×5 every 21 days (regimen I) and topotecan 4.0 mg/m2/day on days 1, 8, and 15 of a 28-day cycle (regimen II). All patients were treated until disease progression, unmanageable toxicity, or patient refusal. Insufficient accrual related to regimen I resulted in a redesign of the study as a single arm phase II trial assessing only regimen II. More complete efficacy data is presented for regimen II as enrollment on regimen I was insufficient for some analyses. RESULTS: A total of 81 patients were enrolled. One patient was ineligible. Fifteen patients received regimen I, while 65 patients were treated with regimen II. The response rate on regimen I (daily×5) was 27% (90% CI: 10-51%) and 12% (90% CI: 6-21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8 months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with daily×5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in both groups. CONCLUSION: The weekly regimen of topotecan appeared less active but resulted in less toxicity than the daily regimen in platinum-sensitive recurrent ovarian cancer patients.

The impact of age on long-term outcome in patients with endometrial cancer treated with postoperative radiation.

PURPOSE: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Age has been associated with worse outcome in univariate analysis. However, the patterns of failure and associated risk factors in older patients remain unclear. We reviewed our institution's experience to assess the effect of age in a population of endometrial cancer patients treated with surgery and adjuvant radiation therapy. METHODS: From 1992-2002, 243 endometrial cancer patients underwent a total abdominal hysterectomy and adjuvant radiation. Forty-nine patients with stage I-II (occult) endometrial adenocarcinoma (no clear cell or serous papillary) were treated postoperatively with vaginal intracavitary high-dose rate (HDR) brachytherapy alone using Iridium-192 (median dose 30 Gy) to a median length of 4 cm. Forty-eight patients with stage I-III endometrial adenocarcinoma (no clear cell or papillary serous) were treated with postoperative pelvic RT (median dose 45 Gy) and intracavitary HDR brachytherapy (median dose 20 Gy). One hundred forty-six patients underwent postoperative whole abdomino-pelvic irradiation (WAPI) secondary to unfavorable histology (clear cell or serous papillary) or two of the following: deep myometrial invasion, grade 3, or FIGO stage III. Age was analyzed as a continuous and a categorical variable. The age of 63 year split the age group using various statistical analyses. RESULTS: Median follow-up of all patients was 4.2 years. Patients grouped by age of < or =63 years or older had similar FIGO stage (P = 0.5), grade (P = 0.09), treatment modality (P = 0.7), and lymphovascular space invasion (LVSI) (P = 0.6). Twenty-five percent (60/243) of patients developed recurrence. Of these failures, 15% (15/102) were age < or =63 years and 32% (45/141) were age >63 years at diagnosis (P = 0.02). For all patients, the 5-year event-free survival (EFS), cause specific survival (CSS), and overall survival (OS) were 64%, 82%, and 72%, respectively. Five-year EFS for patients age < or =63 years and >63 years was 76% vs. 55% (P < 0.001). Five-year OS for age < or =63 years and >63 years was 85% vs. 63% (P < 0.001). Five-year CSS for age < or =63 years and >63 years was 91% vs. 75% (P = 0.003). Various factors were analyzed to determine an association with age. Older patients with stage III-IVA had significantly more failures than patients less than age 63 (P = 0.002). Older patients (>63 years) were found to have serous papillary histology (28%) more often than younger patients (15%) (P = 0.02). Greater depth of invasion was associated with older age (P = 0.01). On univariate analysis, older age (P = 0.003), LVSI (P = 0.002), FIGO stage (P < 0.001), grade (P < 0.001), and depth of invasion (P = 0.03) predicted for failure. On Cox multivariate analysis, older age (P = 0.006, HR 2.83), higher FIGO stage (P = 0.001, HR 1.96), and higher grade (P = 0.002, HR 2.66) were significant prognostic factors for recurrence. No difference was seen between the two age groups from date of surgery and start of radiation. The duration of therapy was not different between the two groups. CONCLUSIONS: Older endometrial cancer (age >63 years) patients have a significantly decreased overall survival, cause-specific survival, and greater risk of recurrence following postoperative RT independent of other prognostic factors and/or treatment technique. The impact of treatment-related variables did not alter the age-related outcome.