Abstract
A combination chemotherapy regimen including both intraperitoneal and intravenous administration has been shown to increase overall survival by 32% in women with advanced ovarian cancer.
The results of a Phase III clinical trial published recently in the New England Journal of Medicine have led the US National Cancer Institute (NCI) to recommend simultaneous intraperitoneal and intravenous chemotherapy in stage III ovarian cancer patients following successful debulking surgery.
“It's very good news,” enthused chief investigator Deborah Armstrong. “A lot of larger institutions have already adopted this approach. At least for today, this is the best thing we can offer our patients.”
A total of 415 women with optimally debulked stage III ovarian cancer were randomized to one of two groups. Half of the women were treated with intravenous paclitaxel followed by intravenous cisplatin, while half were given intravenous paclitaxel followed by intraperitoneal cisplatin and subsequent intraperitoneal paclitaxel. Both regimens were administered every 3 weeks for six cycles.
Patients receiving combined intravenous and intraperitoneal therapy had a mean survival of 66 months, 16 months longer than those receiving intravenous treatment only. There was a 5.5 month increase in mean progression-free survival.
This is the eighth trial of intraperitoneal chemotherapy, in which the drugs are flushed through the peritoneal cavity with water, in ovarian cancer. It is thought to be more effective as it delivers greater concentrations of the drug to the peritoneal cavity, where ovarian cancer is most likely to recur.
“Intraperitoneal therapy is not a new treatment approach, but it has not been widely accepted as the gold standard for women with ovarian cancer,” explained Dr Armstrong. “There has been a prejudice against intraperitoneal therapy in ovarian cancer because it's an old idea, it requires skill and experience for the surgery and for the chemotherapy, and it's more complicated than intravenous chemotherapy. But now we have firm data showing that we should use a combination of intraperitoneal and intravenous chemotherapy in most women with advanced ovarian cancer who have had successful surgery to remove the bulk of their tumor.”
Intraperitoneal chemotherapy was associated with significantly greater side effects, including fatigue, pain, hematological, gastrointestinal and neurological symptoms. These side effects, along with complications related to the abdominal catheter used, meant that only 48% of patients in the intraperitoneal group completed all six cycles of chemotherapy. The drop-out rate in the intravenous group was only 17%. In a related editorial, Stephen Cannistra commented that “it is remarkable that such a clinically meaningful survival advantage was observed, despite the high attrition rate.”
The NCI has issued a clinical announcement to recommend this treatment modality as the optimum for these patients. Andrew C von Eschenbach, Director of the NCI, stated that “the NCI wants to make certain that the results of clinical research are rapidly disseminated to both healthcare providers and patients, in order to ensure that life-enhancing cancer treatments are widely available.” Source: Armstrong DK, Bundy B, Wenzel L et al.: Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N. Engl. J. Med. 354(1), 34–43 (2006).
GnRH agonist increases chances of conception in endometriosis patients undergoing fertility treatment
Women with endometriosis undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are over four-times as likely to become pregnant if they are pretreated with a gonadotropin-releasing hormone (GnRH) agonist, according to a recent review of randomized trials. Furthermore, one of the trials suggested a ninefold increase in live births.
There was, however, insufficient evidence to assess the effect of GnRH treatment on rates of miscarriage, ectopic pregnancies, fetal abnormalities or other maternal or fetal complications.
The analysis, conducted by Hassan Sallam of Alexandria University (Egypt) and colleagues, included three randomized trials with a total of 165 patients. They stated that the conclusion “from these three trials is that the administration of GnRH agonists for a period of 3–6 months prior to IVF or ICSI in women with endometriosis increases the odds of pregnancy by more than fourfold.”
Source: Sallam H, Garcia-Velasco J, Dias S, Arici A: Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst. Rev. (1), CD004635 (2006).
in brief…
Pignol JP, Keller B, Rakovitch E, Sankreacha R, Easton H, Que W: Int. J. Radiat. Oncol. Biol. Phys. 64(1),176–181 (2006).
Demonstrates the feasibility of palladium brachytherapy for adjuvant treatment of early breast cancer. The technique involves the implantation of 103Pd permanent breast seed implants (PBSI) in a 1-h operation under local anesthesia. The procedure was carried out in 16 women after surgery for infiltrating ductal carcinoma of less than 3 cm in diameter. It was well tolerated, with minimal adverse effects, and generated acceptable levels of radiation, leading the authors to recommend further trials.
Buchsbaum GM, Duecy EE, Kerr LA, Huang LS, Guzick DS: Obstet. Gynecol.106(6), 1253–1258 (2005).
Suggests that vaginal delivery does not increase the incidence of urinary incontinence. The investigators compared 101 postmenopausal nulliparous women with their parous postmenopausal sisters. Urinary incontinence was reported in 47.6% of nulliparous women compared with 49.7% of parous women and there was no difference in severity or type of urinary symptoms. There was, however, a strong link in continence status between sisters, suggesting a genetic predisposition towards urinary incontinence.
Kendall A, Dowsett M, Folkerd E, Smith I: Ann. Oncol. (2006) (Epub ahead of print).
Raises the possibility that vaginal estradiol may raise serum levels of estrogen in women receiving aromatase inhibitors to suppress estrogen and prevent breast cancer recurrence. This small study examined seven women receiving aromatase inhibitors before and several weeks after initiating vaginal estradiol therapy. Vaginal estradiol is often prescribed to alleviate atrophic vaginitis caused by aromatase inhibitor therapy. Six of the seven women showed significant increases in serum estrogen after 2 weeks and this increase persisted after 12 weeks in two patients.
Prophylactic hysterectomy may help some women with Lynch syndrome
Women with Lynch syndrome, a genetic mutation that causes an increased risk of colorectal cancer, are also at a high risk for endometrial and ovarian cancer. A study published recently in the New England Journal of Medicine has suggested that prophylactic hysterectomy with bilateral salpingo-oophorectomy effectively prevents these cancers. “Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) have a 40–60% lifetime risk of endometrial cancer and a 10–12% lifetime risk of ovarian cancer,” noted Kathleen M Schmeler and colleagues.
A review of the data on prophylactic hysterectomy in these patients in 1997 found that the evidence was not strong enough to recommend the procedure. “The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain,” commented Dr Schmeler.
The investigators, from the MD Anderson Cancer Center (TX, USA), identified 315 women with the mutation. A total of 61 women who chose to undergo prophylactic hysterectomy and 47 who underwent prophylactic bilateral salpingo-oophorectomy were compared with Lynch-syndrome patients who did not have this surgery. Of the women who underwent prophylactic surgery, none developed endometrial, ovarian or peritoneal cancer. However, of those women with the mutation who did not have surgery, 33% developed endometrial cancer and 5% developed ovarian cancer.
In a related editorial, Kenneth Offit and Noah D Kauff emphasize that “the final judgment regarding the most appropriate methods for gynecologic risk reduction in HNPCC will await the completion of prospective cohort studies assessing the effect of risk-reducing surgery on both cancer incidence and mortality, as compared with gynecologic screening alone. Such a study is currently in development through the Gynecologic Oncology Group.” Source: Schmeler KM, Lynch HT, Chen LM et al.: Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N. Engl. J. Med. 354(3), 261–269 (2006).
Liquid-based cervical cancer tests may be no more effective than conventional tests
A review of published studies, reported in a recent issue of the Lancet, suggests that the newer, liquid-based cytology offers little or no improvement over conventional cytology.
The researchers analyzed the results of 56 studies and found that the number of unsatisfactory slides appeared to be similar with both methods, with a median difference of only 0.17%, and that there was no difference in the number of high-grade cervical lesions.
The authors commented on the lack of high-quality clinical trials on this subject. Only one of the 56 studies was a randomized, controlled trial and only four had enough data to examine the sensitivity and specificity of the two methods of testing.
In a related editorial, Jorg Obwegeser and Volker Schneider commented that “the two messages that come to mind first after reading this paper are that peer review does not automatically indicate high quality, and enthusiasm for new technology should not replace proper study design.”
Source: Davey E, Barratt A, Irwig L et al.: Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review. Lancet 367(9505), 122–132 (2006).
Bone density lower in premenopausal women with Type 1 diabetes
Previous studies have shown a greater risk of fractures in older women with Type 1 diabetes, and the authors of the current study hypothesized that this might be due to a lower bone mineral density (BMD) in younger diabetic women. “Additionally,” added lead author Elsa Strotmeyer, “there is some suggestion from elderly populations that cardiovascular disease may be related to lower BMD, and cardiovascular disease is a common complication of Type 1 diabetes.”
The researchers compared the BMD and fracture histories of 67 women aged 35–55 years with Type 1 diabetes versus 237 nondiabetic controls matched for age, race and socioeconomic status. The diabetic women had 3–8% lower BMD values at the hip, femoral neck, calcaneal bone and whole body.
Women with Type 1 diabetes should consider early screening for osteoporosis, according to a report by investigators at the University of Pittsburgh (PA, USA).
“The difference in BMD for diabetic versus nondiabetic women is between 0.5 and 1 standard deviations for the different sites,” noted Dr Strotmeyer. In addition, over a third of the diabetic women reported a fracture after the age of 20 years compared with less than a quarter of the nondiabetic controls.
The reasons that diabetes affects bone remain unclear, commented Dr Strotmeyer, but “there are many possible theories.” Dr Strotmeyer suggested that poor glycemic control and increased bone turnover are possible mechanisms. She added “our data suggest that clinically diagnosed complications may affect BMD. Though our study did not assess early or subclinical stages of these diabetes complications, this is a future area for research.” Also, she suggests, “it is likely that even subclinical changes in the cardiovascular system, kidney or nervous system in Type 1 diabetes, which are often associated with a longer duration of disease, are influencing bone.”
The authors concluded that “Type 1 diabetic women should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause.”
Source: Strotmeyer ES, Cauley JA, Orchard TJ, Steenkiste AR, Dorman JS: Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women. Diabetes Care 29(2), 306–311 (2006).
New drug for mastalgia
Researchers have demonstrated that toremifen citrate, a derivative of tamoxifen, is effective in relieving the pain of mastalgia. A total of 195 premenopausal women with moderate-to-severe cyclical or noncyclical mastalgia were randomized to receive toremifen or placebo for three menstrual cycles.
Of the women receiving toremifen, 69% achieved a reduction in pain scores of over 50%, compared with 32% receiving placebo. The response to toremifen appeared greater among women with cyclical versus noncyclical mastalgia, with reductions in pain scores of over 50% in 77 versus 48% of patients, respectively, although these differences were not significant. These rates are similar to the responses seen with other mastalgia drugs.
The authors emphasized the lack of adverse events with toremifen, with no significant increase in the incidence of adverse events between toremifen and placebo.
Source: Gong C, Song E, Jia W et al.: A double-blind randomized controlled trial of toremifen therapy for mastalgia. Arch. Surg. 141(1), 43–47 (2006).
Pregnancy does not protect women from relapse of depression
“Pregnancy has historically been described as a time of emotional wellbeing, providing ‘protection’ against psychiatric disorder,” noted Lee S Cohen and colleagues in an article published recently in the Journal of the American Medical Association. “However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.”
The researchers aimed to assess the risk of relapse of major depression in 201 women with a history of major depression, who were receiving antidepressants until they became pregnant. Of these women, 82 continued and 65 discontinued antidepressant treatment, 34 decreased their dose and 20 increased their dose.
In total, 43% of the women experienced a relapse of major depression, and the risk was increased fivefold in women who discontinued their medication, suggesting that pregnancy is not protective against relapse.
“Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation,” suggest the authors.
Source: Cohen LS, Altshuler LL, Harlow BL et al.: Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 295(5), 499–507 (2006).
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