Weekly topotecan in heavily pretreated patients with recurrent epithelial ovarian carcinoma.

OBJECTIVE: To investigate weekly topotecan in heavily pretreated patients with recurrent ovarian cancer. METHODS: The records of patients with recurrent epithelial ovarian cancer who were treated with weekly topotecan after failure of > or =1 prior regimen were reviewed. Patients received topotecan (median starting dose approximately 2.5 mg/m(2)) on days 1, 8, and 15 of a 28-day cycle. Antitumor response was assessed after 2 cycles by serial CA-125 levels. RESULTS: Thirty-five heavily pretreated patients received a mean of 5 cycles of topotecan (range, 1-13 cycles). Thirty-two patients had definable platinum sensitivity (16 sensitive, 8 resistant, 8 refractory). Median age was 56 years. A total of 177 cycles (534 weeks) of topotecan was administered. Hematologic toxicity was generally mild, and no grade 4 toxicities were observed. Grade 3 hematologic toxicity, including leukopenia, neutropenia, thrombocytopenia, and anemia, was observed in 2, 2, 1, and 0 patients, respectively. No patients experienced grade 3 or 4 nonhematologic toxicity. Based on serial CA-125 measurements, there were 1 (3%) complete and 5 (15%) partial responses, with 1 of the partial responses in a patient with platinum-refractory disease. Stable disease was reported in 13 (38%) patients, including 5 patients with platinum-resistant/refractory disease. CONCLUSION: Weekly topotecan demonstrates activity and is well tolerated compared with historical data with the standard 5-day schedule. Higher doses may be warranted because of the high tolerability shown for weekly topotecan. Weekly topotecan may be an appropriate treatment option for patients with recurrent ovarian cancer, especially heavily pretreated patients who might require dosing schedules with improved tolerability.

Fertility preservation options for female patients with malignancies.

PURPOSE OF REVIEW: Preservation of fertility in female patients diagnosed with cancer has recently been an area of intensive investigation. This review summarizes available options and discusses recently published data concerning experimental methods. Specific strategies for fertility preservation in women with gynecologic malignancies are also presented. RECENT FINDINGS: Success with ovarian stimulation protocols using tamoxifen or aromatase inhibitors has recently been reported for women with breast cancer who attempt embryo cryopreservation prior to chemotherapy. The first embryo transfer using oocytes retrieved from cryopreserved ovarian tissue implanted at a heterotopic location, the first pregnancy following orthotopic transplantation of cryopreserved ovarian tissue, and increasing success with oocyte cryopreservation were also reported. SUMMARY: Fertility preservation in female patients with cancer has become an important health issue due to increasing survival rates and delayed childbearing especially in Western countries. Radical vaginal trachelectomy for cervical cancer, conservative surgery for ovarian tumors, and progestin treatment in endometrial cancers may be considered at early stages in order to preserve fertility. Embryo cryopreservation is an established technique that is available for fertility preservation, providing a delay in the initiation of chemotherapy or radiotherapy is acceptable, and a partner or donor sperm is available. Additional techniques that could be offered after counseling the patient about their experimental nature include oocyte cryopreservation, ovarian cryopreservation, and gonadotropin-releasing hormone agonist co-treatment with chemotherapy. Improvement of these techniques as well as better characterization of their success rates and risks await further investigation.

SGK1, a potential regulator of c-fms related breast cancer aggressiveness.

The aggressive behavior of breast cancer cells can at times be modulated by hormonal mechanisms. Exposure to glucocorticoids (GC) has been shown to stimulate the invasiveness, motility and adhesiveness of breast cancer cells containing the glucocorticoid receptor. This is largely explained by GC-associated overexpression of the c-fms proto-oncogene, which encodes the receptor for the colony stimulating factor-1 (CSF-1). Our objective is to investigate additional GC-associated genetic alterations that could modulate c-fms related malignant behavior in breast cancer cells. A microarray technique using an oligonucleotide array representing 16,700 known expressed human genes was used to analyze the gene expression profile of breast cancer cells exposed to dexamethasone (Dex) or vehicle. Results were confirmed by western blot analysis. Six genes were found to be consistently differentially overexpressed in the Dex-exposed cells compared to control. We focused on serum-glucose kinase 1 (SGK1), a serine-threonine kinase known to be involved in intracellular signal transduction pathways and induced by GC and serum. An adhesion assay was performed on extracellular matrix after exposing the breast cancer cells to Dex, CSF-1 or to Dex or CSF-1 plus LY294002, a functional inhibitor of SGK1 action. Exposure to LY294002 significantly decreased both CSF-1 and Dex-induced adhesiveness to the level of control cells. SGK1 may act as a downstream intracellular regulator of c-fms, particularly of c-fms-induced adhesiveness of breast cancer cells after exposure to GC or CSF-1. This finding may have implications for potential therapeutic interventions aimed at decreasing the aggressiveness of breast cancer cells.

Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary.

OBJECTIVE: To analyze the long-term effects on reproductive function of fertility-preserving treatment for malignant germ cell tumors of the ovary. METHODS: A case series analysis was performed on patients with malignant germ cell tumors of the ovary seen or consulted on at our institution between 1975 and 1995. Follow-up information regarding reproductive function was obtained by a mailed or telephone questionnaire. RESULTS: A total of 106 patients with malignant germ cell tumors of the ovary were included in the study. Twenty patients were excluded because of loss of follow-up or death. For the remaining 86 patients, the median follow-up was 122 months (24-384 months). Fertility-preserving surgery was performed in 64 patients. Thirty-eight have attempted conception and 29 have achieved at least one pregnancy (76%). Among the patients who conceived, 20 were International Federation of Gynecology and Obstetrics (FIGO) stage I, one was stage II, and eight were stage III. Sixteen received vincristine, actinomycin D, and cyclophosphamide; three received cisplatin, vinblastine, and bleomycin; three received bleomycin, etoposide, and cisplatin; one received etoposide and cisplatin; four did not receive any chemotherapy; and two were treated with other combinations. Among the nine patients who could not conceive, seven were FIGO stage I and two were stage III. Four of these patients received vincristine, actinomycin D, and cyclophosphamide; three received etoposide and cisplatin; one received cisplatin, vinblastine, and bleomycin; and one patient received no chemotherapy. A total of 38 children were born to these women. Follow-up was available for 16 of these children, who have no evidence of congenital anomalies. CONCLUSION: Fertility-preserving surgery followed by chemotherapy, even in advanced-stage malignant germ cell tumors of the ovary, is effective in conserving the reproductive function of women with malignant germ cell tumors of the ovary.