A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers.

OBJECTIVES: A phase II trial designed to evaluate the safety and efficacy of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine or epithelial ovarian cancers. METHODS: Eligible patients with recurrent epithelial ovarian or uterine cancers were treated with weekly topotecan 3.5 mg/m(2) and docetaxel 30 mg/m(2) for 3 consecutive weeks. Cycles were repeated every 4 weeks for 6 cycles or until evidence of disease progression, unacceptable toxicity, or death. Response was assessed as per RECIST or Rustin's criteria. Time to best response and overall survival were calculated using Kaplan-Meier statistical methods. RESULTS: Twenty-seven patients registered, of which 24 were evaluable for response. The majority of patients had received 2 prior chemotherapy regimens. Of the total 86 cycles of chemotherapy that were administered, there were three grade 4 (all neutropenia) and ten grade 3 toxicities. Six of the grade 3 non-hematologic toxicities were unrelated to treatment. There were 8 dose delays and 4 dose reductions. The overall response rate was 25% (95% CI: 7.7%-42.3%, 8% CR, 17% PR), and 38% of the patients had clinical benefit (95% CI: 18.1%-56.9%; CR+PR+13% SD). The median duration of response was 8.5 months (range 3-19 months). The median overall survival was 18.5 months (range 1.8-50.7 months). CONCLUSION: The combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated patient population. Patients with platinum-resistant tumors had clinical benefit and should be considered for further study with this regimen.

Malignant struma ovarii--a case report and review of the literature.

BACKGROUND: Struma ovarii is a rare monodermal ovarian teratoma composed predominantly of mature thyroid tissue. Of these cases, 5-8% are clinically hyperthyroid and 5-10% of these tumors are malignant. CASE REPORT: A 53-year-old female presented with a 19 x 5 x 5 cm pelvic mass that was treated with bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node sampling, omentectomy and appendectomy and staging for an ovarian tumor. There was no evidence of distant metastases or lymph node invasion. Re-evaluation of the patient after surgery revealed that she was clinically euthyroid and there was no thyroid malignancy. Histopathology revealed papillary thyroid carcinoma arising in struma ovarii (malignant struma ovarii). CONCLUSION: Malignant struma ovarii is a very rare malignant ovarian teratoma. In young patients unilateral oophorectomy and complete surgical staging should be considered when the tumor is confined to the one ovary (stage Ia). Long-term follow-up for the detection of metastases or tumor recurrence by serial serum thyroglobulin and (131)I scan or positron emission tomography/computed tomography may be required in selected patients with this rare tumor.

Prospective evaluation of platelet B2 bradykinin and thrombopoietin receptor levels from preeclamptic compared to non-preeclamptic pregnancy patients.

Our recent study determined a difference between preeclamptic and non-preeclamptic patients in platelet potentiation by thrombopoietin (TPO) of reactivity to collagen. The main conclusion was that non-preeclamptic, but not preeclamptic, pregnancy patients' platelets showed significant TPO potentiation at first and third trimesters. Since TPO or B2 Bradykinin platelet receptor levels might influence TPO potentiation, we obtained platelet samples from 187 first trimester pregnant patients prospectively followed through pregnancy. Patients were additionally sampled at third trimester, delivery, and 4 to 6 weeks postpartum. A total of 43 patients, including 11 diagnosed as preeclamptic at third trimester, were sampled at least three different times. We used Western blotting normalized with glyceraldehyde 3 phosphate dehydrogenase as a loading and staining control. There were no significant differences in relative receptor levels between groups or sampling times using repeated measures ANOVA with the mixed model allowing for missing samples. While the mechanism for differences in thrombopoietin potentiation of platelet activation by collagen remains unknown, it may be a first trimester indicator of developing preeclampsia.

Lack of thrombopoietin potentiation of platelet collagen activation in the first trimester is associated with preeclampsia.

To determine whether a difference exists in platelet reactivity to collagen and potentiation by thrombopoietin (TPO) between preeclamptic and non-preeclamptic patients, 187 first trimester pregnant patients were prospectively followed through pregnancy. Citrated blood, drawn at first (<14 weeks estimated gestational age) and third trimesters (>28 weeks), when patients were admitted for delivery, and 4-6 weeks postpartum, was assayed by a Whole Blood Impedance Aggregometer measuring platelet activation by 0.4 mug/ml collagen, +/-10 ng/ml TPO. There was no significant difference in 1st trimester platelet collagen activation by unpaired t-test between groups. Significant TPO potentiation of collagen activation (P<0.05, paired t-test) was observed in non-preeclamptic patients at the first and third trimesters. In contrast, preeclamptic patients' platelets show no significant (P>0.8, paired t-test) TPO potentiation at any time. While the mechanism for this difference in thrombopoietin potentiation of platelet activation by collagen as early as the first trimester is unknown, it may be one of the initiating events in this syndrome.