A Phase I Study using low-dose fractionated whole abdominal radiotherapy as a chemopotentiator to full-dose cisplatin for optimally debulked stage III/IV carcinoma of the endometrium.

OBJECTIVE: To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma. METHODS: Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit. RESULTS: Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR. CONCLUSION: Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy.

A rat model of preeclampsia.

Preeclampsia/eclampsia is a disorder of human pregnancy that continues to exact significant maternal morbidity and mortality and fetal wastage. Therapy of these disorders has not changed in over 50 years and there are no proven preventive measures. We describe a model of the development of a syndrome in the pregnant rat that resembles preeclampsia, which results from the imposition of excessive volume expansion early in gestation. We administered desoxycorticosterone acetate (DOCA) to pregnant animals whose drinking water had been replaced with saline. We compared the results obtained in these animals with those resulting from the study of control, virgin animals, virgin animals receiving DOCA and saline, and normal pregnant (NP) animals. The virgin animals given DOCA and saline did not become hypertensive. The experimental paradigm in the DOCA plus saline pregnant (PDS) animals provides many of the phenotypic characteristics of the human disorder including the development of hypertension, proteinuria, and intrauterine growth restriction. In addition, the mean blood nitrite/nitrate concentration was reduced in the PDS rats compared with their NP counterparts. We propose that this model may prove to be useful in the study of the human condition.