Justin C. Chura

Brain metastasis from cervical carcinoma.

The aim of this study was to describe the features of patients with brain metastasis from cervical cancer. Twelve patients with brain metastasis from cervical cancer were identified. Information regarding symptoms, treatment, and survival was analyzed. The incidence of brain metastasis in our population was 0.77%. Median patient age at initial diagnosis of cervical cancer was 43.5 years (range 29–57 years) compared with 44.5 years (range 31–58 years) at identification of brain metastasis. Six patients had FIGO stage IB disease; three had stage IIB disease; and one each had stage IIIA, IIIB, and IVB disease. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 17.5 months (range 1.1–96.1 months). All but one patient presented with neurologic symptoms. Eight patients received whole-brain irradiation and steroids, three received steroids alone, and one underwent surgery, followed by irradiation. All the patients who received whole-brain irradiation experienced improvement in their symptoms. Median survival from diagnosis of brain metastasis to death was 2.3 months (range 0.3–7.9 months). Five patients who received chemotherapy after brain irradiation had a median survival of 4.4 months compared to 0.9 months for those who received no additional treatment after brain irradiation (P= .016). Most patients with brain metastasis from cervical cancer presented with neurologic sequelae. Brain irradiation improved these symptoms. Survival after diagnosis of brain metastasis was poor; however, patients who received chemotherapy after brain irradiation appeared to have improved survival.

Steroid-converting enzymes in human ovarian carcinomas

Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17beta-HSD activity ratios with estradiol (E(2)) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17beta-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17beta-HSD, 3alpha-HSD/3-KSR, and 3beta-HSD. E(2)/T activity ratios varied widely between samples. A 17beta-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E(2) formation from estrone sulfate (E(1)S) was detected in 98% (47/48) of the samples. 17beta-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17beta-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy.

Estrone sulfatase activity in patients with advanced ovarian cancer.

INTRODUCTION We sought to identify whether the sulfatase pathway was present in ovarian cancer specimens and then to determine whether a clinical correlation existed between sulfatase activity and survival. MATERIALS AND METHODS Enzymatic activity was assessed in advanced ovarian cancer specimens via thin layer chromatography and standardized against total protein. All enzyme activities are reported in pmol/mg protein/30 min. Kaplan Meier curves of progression-free and overall survival were constructed to compare outcomes between patients with low sulfatase activity and high sulfatase activity. Median survival rates were compared using the log-rank test for survival curves. Differences in proportions between patients with low sulfatase activity versus high sulfatase activity were compared with the z-test or chi-square analysis as appropriate. RESULTS 37 specimens from patients with advanced stage ovarian cancer were analyzed. Enzymatic activity was detected in all specimens except one. Median progression-free survival was 23.5 months for patients with low sulfatase activity compared to 6.9 months for patients with high sulfatase activity (p=0.008). Median overall survival favored the low sulfatase group (50.8 vs. 30.6 months respectively), though statistical difference was not detected (p=0.16). No other difference in clinical characteristics between patients with high or low sulfatase activity was detected. CONCLUSIONS Sulfatase activity is widely present in ovarian cancer specimens. Increased sulfatase activity is associated with worse progression-free survival in patients with advanced stage ovarian cancer. The sulfatase pathway is a potential therapeutic target in the treatment of ovarian cancer.

Ifosfamide, paclitaxel, and carboplatin, a novel triplet regimen for advanced, recurrent, or persistent carcinoma of the cervix: A phase II trial ☆

OBJECTIVES (1) To determine the response rate of advanced, recurrent, or persistent carcinoma of the cervix to ifosfamide, paclitaxel, and carboplatin chemotherapy; (2) to determine the progression free interval and survival rate in patients treated with this regimen; (3) to describe the toxicities associated with this regimen; and (4) to evaluate the quality of life of patients while on treatment. METHODS Eligible patients had histologically proven stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. Chemotherapy was given on day 1 of a 28-day cycle: mesna (600 mg/m(2)) prior to ifosfamide (2 g/m(2)), paclitaxel (175 mg/m(2)), carboplatin (AUC 5). Response rates were determined according to RECIST criteria. Toxicity was graded according the National Cancer Institutes common toxicity criteria. Quality of life measurements were obtained using the FACT-Cx. RESULTS Twenty-eight patients participated in this study, with 21 evaluable for response rate. Overall, 7 patients (33%) had a demonstrated objective response (4 complete responses, 3 partial responses). Stable disease was documented in 3 patients. The overall median survival for all patients was 10 months. Median progression free survival for evaluable patients was 5.0 months. Bone marrow suppression was the most common toxicity. There were no negative effects of this treatment regimen on quality of life assessments. CONCLUSION Ifosfamide, paclitaxel, and carboplatin is an effective regimen in treating advanced or recurrent carcinoma of the cervix and has an acceptable toxicity profile.