Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European–Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin–paclitaxel regimen over cisplatin–cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Background. Studies have suggested that mammographic density and pattern are affected by hormone replacement therapy (HRT) and may influence breast diagnosis. Because 40% of breast cancers diagnosed at our center are mammographically detected while still clinically occult, mammographic sensitivity is crucial. For this reason we studied the effect of HRT on mammographic density. Methods. During a period of 18 months we studied consecutive women older than 54 years attending for breast screening. We recorded HRT use and dosing regimes. A breast density score (BDS) was developed and applied to all mammograms. Results. Mammograms of 148 HRT users were compared with those of 158 nonusers. HRT users had a significantly higher mean density score (4.7 versus 3.4; p < 0.001). Only 11% of non‐HRT users had high scores compare with 37% among HRT users (p < 0.001). The significant difference remained when women were stratified by age. Duration of HRT (longer or shorter than 5 years) did not affect density scores. Conclusion. HRT is associated with a significant increase in breast density. In turn, density and mammographic sensitivity are related. The possibility that increased breast density will hamper mammographic diagnosis of clinically occult cancers is worrisome.

Logically, the choice of any ultimate optimum therapy requires, as well as comparison of the survival outcomes, a comparison of both subjective and objective toxicities in terms of incidence, degree of severity, and duration. Frequently such detail is not collected in large studies. Both cisplatin and paclitaxel are effective but neurotoxic drugs for ovarian cancer. The optimum choice is further complicated in that carboplatin is a possible alternative for cisplatin, being less neurotoxic but having greater hematologic toxicity. Similarly, 3-h and 24-h infusion schedules of paclitaxel have different incidences in opposite directions of hematologic and neurologic toxicities. One hundred fifty two eligible Canadian patients entered in a European-Canadian study that compared paclitaxel-cisplatin (PT, 79) patients with cyclophosphamide-cisplatin (PC, 73 patients) had both subjective and objective neurotoxicity data collected from treatment initiation to disease progression. Incidence, degree, and duration (compared in an analogous way to remission durations) of neurotoxicity were compared in the two arms to quantify the additional paclitaxel toxicity. No significant differences were found for motor toxicity, motor impairment, hearing impairment, or insomnia. For sensory changes during treatment, toxicity (all grades, 91% vs. 49%; grade 3 or higher, 29% vs. 3%) incidence, subjective impairment (a little or more, 89% vs. 40%; lots, 54% vs. 11%) incidence, and toxicity duration (all grades only), and impairment durations (both degrees) were all worse for PT. During follow-up, only the incidence of all-grade sensory toxicity was worse and this was not reflected by any other parameters. We conclude that paclitaxel adds considerably, but only temporarily, to the sensoy neurotoxicity of cisplatin.

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