Monday, April 12, 2010
commentary/Japanese study - Carbo/Taxol - Dose-Dense Chemotherapy for Ovarian Cancer - National Cancer Institute
"...Women with advanced ovarian cancer lived longer and without their tumors growing after receiving a modified regimen of a standard chemotherapy drug combination, Japanese researchers have reported. In a large phase III clinical trial, the researchers randomly assigned women to receive six cycles of carboplatin and paclitaxel (Taxol) every 3 weeks (standard regimen) or six cycles of carboplatin every 3 weeks and a lower dose of paclitaxel (Taxol) once a week (dose-dense regimen). Women in the dose-dense group had a 29 percent reduction in the risk of progression and a 25 percent reduction in the risk of death after 3 years of follow-up. The results were published online September 18, 2009, in The Lancet (see the journal abstract).
Although the dose-dense regimen had more toxic effects than the standard regimen, survival benefits of this magnitude "have been rare in women with advanced ovarian cancer," wrote. Noriyuki Katsumata, M.D., and colleagues from the Japanese Gynecologic Oncology Group (JGOG).
The results, explained Ted Trimble, M.D., M.P.H., from NCI's Division of Cancer Treatment and Diagnosis, are consistent with what has been seen in breast cancer using a dose-dense chemotherapy regimen. The idea, he continued, is "to balance efficacy and toxicity by using a weekly schedule rather than every 3 weeks."...."
Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material.
Authors’ conclusions There is little evidence from randomised controlled trials of the effects of consumer involvement in healthcare decisions at the population level. The trials included in this review demonstrate that randomised controlled trials are feasible for providing evidence about the effects of involving consumers in these decisions.
Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands.
CONCLUSIONS: Lynch syndrome mutation carriers have a substantial risk for gastric cancer, in particular patients with an MLH1 or MSH2 mutation. Family history for gastric cancer is a poor indicator for individual risk. Surveillance gastroscopy for Lynch syndrome patients carrying an MLH1 or MSH2 mutation should therefore be considered.
CONCLUSION: The majority of the uterine cornua had a tubal remnant which suggests that RRSO may leave behind residual tubal epithelium. The clinical significance of this tubal remnant is unclear given the current understanding of tubal carcinogenesis
Referral and ascertainment bias in patients with synchronous and metachronous endometrial malignancy.
The purpose of this study was to evaluate the frequency in patients with endometrial cancer of other malignancies and the influence of referral and ascertainment biases on these associations.
Analysis of 1,028 local and referred patients who had a hysterectomy for endometrial cancer was based on residence at the time of diagnosis.
Altogether, 208 patients had a history of another malignancy, most frequently breast, colon, and ovary. At the time of surgery for endometrial cancer, the prevalence of lymphoma and breast and ovarian cancers was greater than expected although the higher prevalence of lymphoma was limited to referred patients. During follow-up after hysterectomy, the incidence of lung cancer was lower than expected, whereas the incidence of lymphoma was higher. Breast, colorectal, and bladder cancers were more common than expected although this finding was limited to local patients.
We concluded that results of epidemiologic studies from tertiary care centers may be misleading if they do not account for referral and ascertainment biases.
"As the preclinical results of mAb's therapeutic effects on ovarian cancer have been encouraging, further investigations are needed to establish a more effective, specific, and less toxic treatment strategy for this malignancy."
Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with re
dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
"CONCLUSIONS: Imaging markers have a potential role in early prediction of disease progression in patients with residual ovarian cancer and may supplement current measures of progression. The correlation of DCE-MRI and serological biomarkers suggests that tumour angiogenesis affects these markers through common biological means and warrants further investigation."
Low malignant potential tumors with micropapillary features are molecularly similar to low-grade serous carcinoma of the ovary.
CONCLUSION: The gene expression profile of LMP-MP is similar to LGSC and distinct from LMP, reflecting their more aggressive clinical behavior. *Low-grade serous carcinoma (LGSC) *LMP with micropapillary features (LMP-MP)
Cancer Causes Control. 2010 Mar 23
"We performed case-control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC).
Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women....Although many case-control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were >/=35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk.
We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers.
A larger study to determine risk factors for invasive serous PPC is warranted."
CONCLUSIONS:: Lynch syndrome is under-recognized, even when patients have clear criteria unrelated to family history. Multifaceted strategies focused on reducing providers' cognitive errors and harnessing EHR (electronic health record) capabilities to improve recognition of Lynch syndrome are needed "Among 244 patients with uncertainty, a suspicion for Lynch syndrome was documented in the EHR of 6 patients (2.5%); 3 received counseling."
Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms
"Endometrial and ovarian carcinomas with undifferentiated components have a broad histologic differential diagnosis, but they show specific histologic features that should enable accurate diagnosis. These tumors can occur in young women, may be associated with microsatellite instability and behave in a clinically aggressive manner." Modern Pathology
Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer.
Low-dose metronomic chemotherapy has shown promising activity in many preclinical and some phase II clinical studies involving various tumor types. To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic chemotherapy regimens alone or in concurrent combination with an antiangiogenic drug, pazopanib. Clones of the SKOV-3 human ovarian carcinoma cell line expressing a secretable beta-subunit of human choriogonadotropic (beta-hCG) protein and firefly luciferase were generated and evaluated for growth after orthotopic (i.p.) injection into severe combined immunodeficient mice; a highly aggressive clone, SKOV-3-13, was selected for further study. Mice were treated beginning 10 to 14 days after injection of cells when evidence of carcinomatosis-like disease in the peritoneum was established as assessed by imaging analysis. Chemotherapy drugs tested for initial experiments included oral cyclophosphamide, injected irinotecan or paclitaxel alone or in doublet combinations with cyclophosphamide; the results indicated that metronomic cyclophosphamide had no antitumor activity whereas metronomic irinotecan had potent activity. We therefore tested an oral topoisomerase-1 inhibitor, oral topotecan, at optimal biological dose of 1 mg/kg/d. Metronomic oral topotecan showed excellent antitumor activity, the extent of which was significantly enhanced by concurrent pazopanib, which itself had only modest activity, with 100% survival values of the drug combination after six months of continuous therapy. In conclusion, oral topotecan may be an ideal agent to consider for clinical trial assessment of metronomic chemotherapy for ovarian cancer, especially when combined with an antiangiogenic drug targeting the vascular endothelial growth factor pathway, such as pazopanib. Mol Cancer Ther; 9(4); 996-1006. (c)2010 AACR.
CA 125 and the detection of recurrent ovarian cancer. Robert C. Bast Jr. 2010; Cancer - Wiley InterScience
CA 125 and the detection of recurrent ovarian cancer
A reasonably accurate biomarker for a difficult disease
|Robert C. Bast Jr, MD|
|Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas|
|Rising cancer antigen 125 (CA125) levels have been used to detect recurrence of ovarian cancer. A recent study questions the value of this practice, but the clinical trial has significant limitations and discounts the value of early detection to permit treatment of recurrence with novel and conventional agents.|
British Journal of Cancer -Age of mother and grandmother in relation to a subject's breast cancer risk
Background: On theoretical grounds, the age of the grandmother and the age of the mother at delivery of her daughter may affect the breast cancer risk of the granddaughter.
Conclusion: This study does not suggest a major role of maternal age at delivery or grandmaternal age at delivery of the mother for the (grand)daughters' breast cancer risk.
FDA & Digital Mammography: Why Has FDA Required Full Field Digital Mammography Systems to Be Regulated as Potentially Dangerous Devices for More Than 10 Years?
author: Bioptics Inc.
(Promestriene) Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy; Gynecological Endocrinology
"Given the absence of systemic activity, promestriene may be a good choice in women requiring purely locally oestrogen, and those who have survived, or who are at risk of breast cancer and who have severe vulvo-vaginal symptoms."
Strength in Numbers
Project plans to unite support services for women with breast and reproductive cancers
By Jane Shulman
Cancer support networks in different parts of the country are looking at grouping women’s gynaecological cancers with breast cancer for the purpose of offering more support to women who have had a cervical, ovarian or uterine cancer diagnosis. Manitoba has been working on this for some time, explains Barbara Clow, director of the Atlantic Centre of Excellence for Women’s Health, and now New Brunswick and Newfoundland and Labrador are looking at their own models for delivering programming under the same umbrella.
In a 2008 report for Canadian Partnership Against Cancer, called “Where Do We Go From Here? Support services for women with breast, cervical, ovarian and uterine cancer in Atlantic Canada,” Clow and co-authors looked at the idea of merging services to meet the needs of the underserved gynaecological cancer population.
The idea is not without its detractors. Some have expressed concern that breast cancer groups might jeopardize their funding or lose their identity if they expand their mandate, or stretch their already overextended resources.
But the focus on breast cancer over the past several years, with fundraisers and awareness campaigns popping up all over the country, means that the disease has a lot of attention, and Clow notes that it’s the kind of attention that gynaecological cancers desperately need. While she says that fewer women are diagnosed with cervical, ovarian and uterine cancers combined than breast cancer in Canada each year, with the exception of cervical cancer, their prognosis is not as good. And the psychosocial support specific to their kind of cancer just does not exist.
Clow cites the work of volunteer-based Ovarian Cancer Canada as the only national gynaecologically-based cancer group. There are no national groups for people with cervical or uterine cancer. The needs are different, but there’s overlap, which is why a program that pools resources for cancers that affect women is so appealing.
The report recommendations included:
Foster new research on the needs of women from vulnerable and disadvantaged communities who are faced with a diagnosis of cancer;
Explore the possibility of adopting and adapting the processes and products developed by breast cancer support networks in Atlantic Canada to meet the needs of those with other women’s cancers;
Promote the creation of publicly funded cancer patient navigator programs throughout Atlantic Canada.
Clow says the next step is to look at how feasible this idea is, and where the desire lies. So far, nurses and service providers involved with the planning and delivering of programming are most passionate about it because they see the possibilities that lie in making the most of the services they can offer.
Jane Shulman is a the Director of Knowledge Exchange at the Canadian Women’s Health Network and a former staff member of Breast Cancer Action Montreal
Emerging drugs for the management of cancer treatment induced bone loss; Expert Opinion on Emerging Drugs
Take home message: The very high rate of bone loss and the high incidence of fractures indicate that cancer patients at risk of CTIBL (cancer treatment induced bone loss) need to be carefully monitored and stratified for fracture risk. Although there is a strong evidence of efficacy in prevention of bone loss and reduction of fracture risk for many drugs approved for postmenopausal osteoporosis (PMO) and male osteoporosis, for CTIBL there are actually no drugs approved for this indication.
The Lancet Oncology, Early Online Publication, 1 April 2010
Targeted therapies for rare gynaecological cancers
All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings.
Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options.