Phase II Study Evaluating PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecologic Sarcomas and Mixed Epithelial-Mesenchymal Tumors A Phase II Protocol of the Arbeitsgemeinschaft Gynaekologische Onkologie Study Group (AGO-GYN 7).

BACKGROUND: Gynecologic sarcomas are rare diseases with still undefined optimal treatment. Platinum and anthracyclines were reported as active agents in gynecologic sarcoma and carcinosarcoma. So far, data regarding the combination of carboplatin and pegylated liposomal doxorubicin for this patient population are missing. METHODS: This prospective single-arm multicenter phase II trial evaluated the efficacy of carboplatin AUC 6 in combination with pegylated liposomal doxorubicin 40 mg/m q28 in 40 patients with newly diagnosed or recurrent gynecologic sarcoma or carcinosarcoma. RESULTS: Twenty patients with carcinosarcoma and 20 patients with leiomyosarcoma or endometrial stromal sarcoma were included. The percentage of patients with grade 3/4 neutropenia was 50%, but we did not observe any febrile neutropenia. The rates of grade 1 and 2 palmo-plantar erythema were moderate with 25% and 10%, respectively. Response rate was 33.3%. The 12-month progression-free and overall survival times were 32.5% and 77.0%, respectively. CONCLUSIONS: The combination of carboplatin and pegylated liposomal doxorubicin is feasible and has activity within the investigated study cohort.

Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13).

BACKGROUND: PLD is a standard treatment in patients with recurrent platinum-resistant or refractory ovarian cancer. Vandetanib is an oral once daily administered inhibitor of VEGFR-, EGFR- and RET-signaling with activity in combination with chemotherapy in some solid tumours. We aimed to establish a feasible combination therapy of PLD and vandetanib in ovarian cancer. METHODS: Eligible patients were treated with PLD 50 mg/m(2) q28 and vandetanib 100 mg/d po. It was planned to recruit at least 10 patients evaluable for toxicity over 2 treatment cycles. Primary endpoints were tolerability and safety; secondary endpoint was efficacy. RESULTS: Fourteen of 15 registered patients started treatment and were evaluable for toxicity. Three patients (21%) stopped after first cycle (PD, withdrawal of consent, nausea/vomiting). The remaining 11 patients were treated for at least 2 cycles. Dose reductions of PLD and vandetanib were indicated in 4 (29%) and 5 patients (36%), respectively. The following G3/4 toxicities occurred per patient: 2 (14%) elevated liver enzymes G3, 2 (14%) neutropenia G3/4, 5 (36%) PPE G3/4, 2 (14%) mucositis G3. Tyrosine kinase inhibitor attributed side effects like hypertension or bowel perforations were not reported. Toxicity led to cessation of treatment in 4 patients (29%). Ten patients were evaluable for response: PR 1, SD 4. The median PFS was 6.7 months and median OS was 11.1 months. CONCLUSIONS: The combination of PLD 50 mg/m(2)q28 and vandetanib 100 mg/d is feasible, but may be intolerable due to reported toxicity.

Spontaneous delivery following tension-free vaginal tape procedure.

There has been no report in the international literature concerning vaginal delivery following tension-free vaginal tape (TVT) procedure. Most gynecologists recommend cesarean section after TVT procedure. We present the case of a 37-year-old (gravida 2, para 2) woman who had spontaneous delivery at 40 weeks' gestation after TVT procedure performed 10 months prior because of stress urinary incontinence. Five months after spontaneous delivery, the patient was shown to be continent, with no urinary leakage occurring following stress maneuver. Urodynamic evaluation showed normal urethral pressure profile and sufficient maximum urethral closure pressure. Introital ultrasound demonstrated the correct position of the Prolene tape. In cases of pregnancy following TVT procedure, a general recommendation of delivery by cesarean section may be questioned, since the function and correct suburethral position of the Prolene tape can also remain intact following vaginal delivery.