James B. Hall

The phosphoprotein Op18/stathmin is differentially expressed in ovarian cancer.

Abstract To identify potential prognostic indicators of ovarian cancer and identify targets for therapeutic strategies, mRNA differential display was used to analyze gene expression differences in normal, benign, and cancerous ovarian tissue. One cDNA isolated by this technique, Op18/stathmin, is a highly conserved gene that is reported to have many different functions within a cell, including signal transduction, control of the cell cycle, and the regulation of microtubules. Quantitative Northern blot analysis of 12 malignant ovarian samples, 8 benign ovarian tumors, and 10 normal ovarian tissue samples demonstrated overexpresaion of Op18/stathmin mRNA in the malignant cancers. Immunohistochemistry showed an apparent overex-pression of Op18/stathmin protein level and an association with proliferating cells

Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer.

Objective: To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC). Methods: Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m2 and PLD at 50 mg/m2 intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis. Results: The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitis was lower on canfosfamide + PLD (23%, 31%, respectively) versus (39%, 49%, respectively) on PLD. Conclusions: Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned. This study was registered at www.clinicaltrials.gov: NCT00350948.

Concurrent carboplatin with pelvic radiation therapy in the primary treatment of cervix cancer

OBJECTIVES The objectives were to determine the acute toxicities of concurrent carboplatin and radiation therapy in the primary treatment of cervix cancer and to ascertain the antitumor activity of this regimen. METHODS Patients with stage IB-1 to IVA untreated primary cervix cancers were eligible for enrollment into this study. Carboplatin was administered on a weekly basis with external radiation therapy (ERT). Low-dose brachytherapy was given after completion of ERT. Acute toxicities and response to treatment were assessed. RESULTS Thirty-one evaluable patients were enrolled. The majority of patients had early stage disease. Carboplatin was successfully administered in 175 out of 186 (94%) planned treatments. All patients completed the prescribed course of radiation therapy. The mean treatment time was 50 days (36-73). There were no treatment delays for neutropenia or gastrointestinal toxicity. No patient was hospitalized for treatment related toxicities. Gastrointestinal toxicity equivalent to grade 3 or 4 was not reported. The objective tumor response based on physical exam findings and computed tomography measurements was 90%. CONCLUSION Patients with cervix cancer can be treated on schedule with concurrent carboplatin and pelvic radiation therapy. This regimen is well tolerated and produces excellent response rates.

Unbalanced estrogen metabolism in ovarian cancer

Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age‐matched controls. Thirty‐eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen–DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p < 0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen‐metabolizing enzymes. Women with two low‐activity alleles of catechol‐O‐methyltransferase plus one or two high‐activity alleles of cytochrome P450 1B1 had higher levels of estrogen–DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen–DNA adducts plays a critical role in the initiation of ovarian cancer.

Primary care by obstetricians and gynecologists: Attitudes of the members of The South Atlantic Association of Obstetricians and Gynecologists

OBJECTIVE Our purpose was to determine the extent of primary care delivered by obstetrician-gynecologists and compare practice patterns with published primary care and preventive service guidelines. STUDY DESIGN All 277 active fellows of The South Atlantic Association of Obstetricians and Gynecologists were mailed a self-administered questionnaire. The type of primary care offered by these physicians and their attitudes about the training of residents in obstetrics and gynecology were surveyed. Physicians were categorized as generalists or specialists on the basis of the completion of a fellowship program. Descriptive statistics and chi 2 analysis were used for statistical analysis. RESULTS Completed surveys were returned by 82% of the fellows. The majority of the respondents perceived their practice as specialty care for women. Generalists offered recommended screening services to women of all ages with greater frequency than the specialists did (p = 0.05). Both groups did not provide care for the chronic medical illnesses most commonly seen in a primary care practice. The respondents favored more residency training in those common acute illnesses frequently encountered in a primary care setting. CONCLUSIONS Obstetrician-gynecologists in The South Atlantic Association of Obstetricians and Gynecologists selectively practice primary care. These physicians did not support caring for chronic medical problems frequently treated in an ambulatory care practice.