Objective. Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of radiosensitizing agents. However, administration of radiosensitizing chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of radiosensitizing chemotherapeutics to the cervix while limiting systemic toxicities.Methods. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CeiviPrep (TM)). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite 2',2'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods.Results. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/g tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/g tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject.Conclusions. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for radiosensitization. (C) 2012 Elsevier Inc. All rights reserved.

Objective. This is a phase II group-wide study of liposomal doxorubicin chemotherapy in patients with advanced or recurrent uterine leiomyosarcomas. The aim was to evaluate clinical response and toxicity.Methods. Patients with histologically confirmed persistent or recurrent leiomyosarcomas of the uterus with documented disease progression after appropriate local therapy were invited to participate in this study. Bidimensionally measurable disease, GOG performance status of 0, 1, or 2 (Karnofsky 80-100) was required; all patients must have failed local therapeutic measures and be considered incurable. Other eligibility criteria included adequate hepatic, renal, and hematologic function. Patients were ineligible if they had received previous chemotherapy or had other noncutaneous malignancies. Patients received liposomal doxorubicin 50 mg/m(2) IV over 1 h. Courses were repeated every 4 weeks until disease progression or adverse side effects supervened.Results. Thirty-five patients were entered into this study between May 2000 and June 2001. Three patients were determined ineligible because of wrong pathological cell type or inadequate pathology information and one was inevaluable for lack of data. Median age was 52 years (range 36-78 years). GOG performance status was 2 in 1 instance, 1 in 15 cases, and 0 in 15 others. Eleven patients (35.5%) had received radiotherapy. A median of 2.0 courses was given (range 1-8). Five patients (16.1%) experienced grade 3 or 4 neutropenia, and seven (22.6%) had grade 3 or 4 anemia. Two patients developed grade 3 and one patient developed grade 4 cardiovascular adverse events, not necessarily drug related. There were seven cases of grade 3 or 4 gastrointestinal toxicity and two patients developed grade 3 dermatologic toxicity. One complete (3.2%) and four partial (12.9%) responses were reported. Ten patients (32.3%) had stable disease, 15 (48.4%) had increasing disease, and response could not be assessed in 1 (3.2%).Conclusion. The dose and schedule of liposomal doxorubicin employed in this trial showed no advantage over historical results with doxorubicin in the treatment of uterine leiomyosarcoma. (c) 2004 Elsevier Inc. All rights reserved.