Dawn L. Hershman

Treatment of hot flushes in breast and prostate cancer

Hot flushes, the most common health problem reported by menopausal-age women, can lead to significant morbidity and affect the social life, ability to work and sleep pattern of the sufferer. Women treated for breast cancer and men receiving androgen ablation for prostate cancer experience hot flushes that are more frequent, severe and longer lasting than those experienced by the general menopausal population. In women with breast cancer, hot flushes can result from chemotherapy-induced menopause, hormonal therapy, or ovarian suppression. In men with prostate cancer, hot flushes occur after surgical or medical castration. Hormone replacement therapy with oestrogen-based compounds has been a mainstay of treatment for hot flushes during the perimenopausal period. However, recent studies have shown that, in healthy menopausal women, hormone replacement therapy is associated with an increased risk of breast cancer, myocardial infarction, thrombo-embolic events and stroke. Thus, identifying nonhormonal agents that can control hot-flush symptoms is essential to the quality of life of a growing population of cancer survivors. The most promising agents act on the CNS and include selective serotonin reuptake inhibitors, as well as venlafaxine and gabapentin.

Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer: a New York Cancer Consortium Study.

OBJECTIVE Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer. METHODS Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simons two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods. RESULTS Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% CI: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% CI: 14.7, 27.2) and mean overall survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths. CONCLUSIONS The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted.

Reply to L. Gianni et al

We thank Gianni et al for their interest in our recent report “Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor–Induced Musculoskeletal Pain: SWOG S0927.” Many of the points raised were addressed in the discussion section of our article. In all trials, difficult choices must be made with regard to the design of the study that may influence the results, such as the choice of outcome measure, the duration of therapy, the dose of drug, the formulation of the drug, the inclusion criteria, and the choice of placebo. In addition, overall negative findings do not preclude the fact that some subsets may achieve more of a benefit than others. In our trial, ongoing analyses will explore factors that may differentiate patients who did and did not achieve an improvement in symptoms over time, both in the active arm as well as the placebo arm, which may inform future studies. But importantly, the patients in the randomized arms of this large multicenter trial were well balanced across multiple domains of potential confounding factors, and overall, the trial did not find a benefit of omega-3 fatty acids compared with placebo. Although it is possible that another rigorous trial could observe a benefit, we do not feel there is sufficient evidence to suggest there is a role for omega-3 fatty acids for treating aromatase inhibitor–induced arthralgias.