Remission of refractory gestational trophoblastic disease in the brain with ifosfamide, carboplatin, and etoposide (ICE): first report and review of literature.

Gestational trophoblastic disease (GTD) metastatic to the brain has a very poor prognosis with a survival rate of less than 25%, especially for patients in whom brain metastases develop while on or after chemotherapy. Cure can be achieved by chemotherapy alone. The regimen of etoposide, methotrexate, actinomycin-D, vincristine, and cyclophosphamide has shown encouraging results and is considered to be standard first-line treatment for high risk patients. For patients in whom this regimen fails, a salvage chemotherapy regimen is used. The combination of ifosfamide, carboplatin, and etoposide (ICE) has synergistic activity in preclinical studies. This regimen has shown activity in metastatic breast cancer and non-small-cell lung cancer as well as platinum-resistant germ-cell tumors and metastatic GTD. This is the first report of a patient with a highly refractory GTD in whom brain metastasis developed while on chemotherapy, and whose brain metastasis went into remission with a low dose ICE regimen. Accordingly, ICE may be considered for patients with chemotherapy refractory GTD metastatic to the brain.

Prolonged oral etoposide for advanced uterine leiomyosarcoma with pulmonary metastases: case report.

A patient who had a high grade uterine leiomyosarcoma with intraabdominal and pulmonary metastases at the time of diagnosis underwent supracervical hysterectomy, bilateral salpingo-oophorectomy and tumor reductive surgery. Induction chemotherapy achieved a partial response with small amount of residual disease. On achieving a plateau in the response to her induction chemotherapy, she was switched to prolonged oral etoposide at a dose of 50 mg/m2/day 21 days with a 7-day rest period between cycles. Follow up imaging revealed stable disease with a slight decrease in the size of the paraaortic lymphnodes. Prolonged oral etoposide may be considered in patients with advanced high grade leiomyosarcoma of the uterus.

A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix.

A Phase I study of the novel angiogenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP-470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.

Recurrent and metastatic cervical carcinoma has very poor prognosis, mainly because there is no effective systemic therapy which would increase the duration of survival. Biologic agents have recently been found to have activity in cervical carcinoma. The combination of interferon (IFN)-alpha and 13-cis-retinoic acid had additive and synergistic antitumor activity. Both have antiviral, immunoregulatory and antiangiogenic properties, and are known to modulate malignant cell differentiation and proliferation. We report two patients with recurrent squamous cell carcinoma (SCC) of the cervix who had small-volume progressive metastatic disease, and were treated with a combination of IFN-alpha and 13-cis-retinoic acid. The first patient had pelvic lymph node metastases and the other had lung metastases. The previously progressive diseases remained stable for a prolonged period of time, 3 and 4 years, with a good quality of life. These cases suggest the possibility of using IFN-alpha and 13-cis-retinoic acid as a treatment for small-volume residual disease or as postinduction therapy in patients at high risk for disease recurrence.

Remission of refractory gestational trophoblastic disease with high-dose paclitaxel.

High-risk metastatic gestational trophoblastic disease (GTD) in patients who have failed primary chemotherapy has a very poor prognosis. About 25% of women with high-risk metastatic disease become refractory to EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide and vincristine) and fall to achieve a complete remission. Currently, there is no standard salvage chemotherapeutic regime for EMA-CO failure. Paclitaxel, a taxane analog extracted from the bark of the western yew (Taxus brevlfolla), has shown antitumor activity in a variety of cancer cell lines. High in vivo efficacy was confirmed in phase II trials, especially for breast and epithelial ovarian cancer patients. Recently, two in vitro studies have shown that paclitaxel is a highly effective antineoplastic agent in choriocarcinoma cell lines. We present the first clinical report of a serologic remission with high-dose paclitaxel (250 mg/m2 i.v. infusion over 24 h every 3 weeks) of a highly refractory GTD in a patient who developed brain metastasis after multiple combined chemotherapeutic regimens. The patient tolerated paclitaxel with granulocyte colony stimulating factor support very well. The remission with paclitaxel in this patient confirms its preclinical activity in high-risk, refractory GTD.

Remission of recurrent cervical cancer with paclitaxel and carboplatin: a case report and review of literature.

We report the case of a patient with recurrent squamous cell carcinoma of the cervix, that metastasized to the paraaortic and supraclavicular lymph nodes and the lungs after primary radiotherapy for stage IIB. The tumor was refractory to multiple drug regimens. A combination of paclitaxel (135 mg/m2 intravenous infusion over 24) hours and carboplatin with a target area under the curve of 7.5 mg-min/mL were then administered and repeated every 4 weeks. The patient tolerated the chemotherapy well with myeloprotection from granulocyte colony-stimulating factor and the disease went into remission. Thus, the combination of paclitaxel and carboplatin may have antitumor activity in advanced or recurrent squamous cell carcinoma of the cervix.