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Saturday, April 28, 2012

Rivkin Center (Seattle) awards grant for cognitive study (ovarian cancer/chemobrain)



 Blogger's Note: many ovarian cancer survivors who have gone before us would be happy with this news (Shirley Inveen, Sheryl Eisenbarth.....)

Rivkin Center awards grant for cognitive study:

CONGRATULATIONS DR. GRAY!

Heidi Gray, MD

University of Washington


Behavioral and neural indices of cognitive rehabilitation in ovarian cancer
Millions of ovarian cancer survivors live with residual symptoms of impaired thinking and impaired memory severe enough to interfere with basic activities of daily living and work. However, very little is known about how to treat problems in cognition. Pharmacologic interventions have only been modestly helpful, if at all, and not all patients desire or are able to take medications. Dr. Gray will examine the ability of a 7-week cognitive rehabilitation intervention to improve memory and thinking abilities in ovarian cancer survivors. In addition, the project will measure changes in brain activity patterns from the treatment using neuroimaging.

Marsha Rivkin Center for Ovarian Cancer Research | supporting research in honor of our wives, mothers, sisters, and daughters
The Rivkin Center is delighted to announce the recipients of its 2012 Scientific Grants.

press release: Moffitt Cancer Center researchers: Quality of life as important as quantity of life



Moffitt Cancer Center researchers: Quality of life as important as quantity of life

"The question of how well people are surviving cancer is as important as how long they survive cancer," .....


Prolonged fatigue after treatment


In a recent study published in Cancer, researchers from Moffitt found that when patients treated with chemotherapy or chemotherapy and radiation for breast cancer were compared to a control group who had not had cancer, the patients who had experienced chemotherapy and/or radiotherapy had more fatigue. These patients also had fatigue that lasted years after their therapy.
"This finding was contrary to our expectations," Jacobsen said. "Conventional thinking is that patients receiving chemotherapy would, over time, experience less fatigue and would eventually see their fatigue diminish to the levels of controls who had not had cancer, or to the level of fatigue they had prior to their chemotherapy.".......

Reply to W.R. Robinson from Chi: re: “Is the Easier Way Ever the Better Way? (ovarian cancer/neoadjuvant therapy/surgery/references...)



 Blogger's Note: follows to prior posting/correspondence/dialogue; worthwhile reading this discussion/debate, note the common denominator in references
           ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Reply to W.R. Robinson

Reply to W.R. Robinson

  1. Dennis S. Chi
  1. Memorial Sloan-Kettering Cancer Center, New York, NY
  1. Corresponding author: Dennis S. Chi, MD, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: gynbreast@mskcc.org.
  1. Robert E. Bristow
  1. University of California, Irvine Medical Center, Orange, CA
  1. Deborah K. Armstrong
  1. Johns Hopkins Kimmel Cancer Center, Baltimore, MD
  1. Beth Y. Karlan
+ Author Affiliations
  1. Cedars-Sinai Medical Center, Los Angeles, CA
We thank Robinson1 for his comments on our editorial, “Is the Easier Way Ever the Better Way?”2 Robinson disagreed with our article on two points. First, he stated that it is “both disingenuous and unrealistic to… suggest that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer.” Robinson also expressed concern that we were suggesting that neoadjuvant chemotherapy (NACT) “somehow represents a failure on the part of the physicians who are taking ‘the easy way out.'”
To the first point, we did not say that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer. Rather, we wanted to highlight that the number of patients who receive suboptimal debulking could be reduced by collaboration with other surgical colleagues. Many gynecologic oncologists partner with urologists for complex continent urinary conduits after pelvic exenteration and with plastic surgeons for a myocutaneous flap after radical pelvic surgery, for example, and we believe that patients with ovarian cancer should also be offered the potential benefit of subspecialty surgical consultation if it will improve their overall survival. The complexity of preplanning surgical consultations for advanced ovarian cancer debulking surgery should not be any different than for these other surgical collaborations.
It is incumbent on the gynecologic oncologist to ensure that pressures to minimize operating room and intensive care unit usage do not compromise the surgical outcome for our patients.........

The author(s) indicated no potential conflicts of interest.

REFERENCES

Friday, April 27, 2012

Correspondence: Neoadjuvant Chemotherapy (ovarian cancer) Is Rarely the Easy Way Out + references +discussion on gyn specialists/general surgeons



Blogger's Note: worthwhile reading/pondering...
             ~~~~~~~~~~~~~

Neoadjuvant Chemotherapy Is Rarely the Easy Way Out

 To the Editor:
I appreciate the thoughtful analysis by Chi et al1 in the November 1 issue of Journal of Clinical Oncology, in the article entitled, “Is the Easier Way Ever the Better Way?” Chi et al make a very literate argument against using neoadjuvant chemotherapy (NACT) for ovarian cancer, continuing a discussion that has lingered among oncologists for more than 25 years. The argument has heated up recently as a result of several prospective studies, particularly that of Vergote et al,2 which showed no difference in survival in patients treated with either primary surgery or NACT.
I must, however, disagree with Chi et al1 on two points. The first of these is the suggestion by the authors that patients with stage IIIC/IV ovarian cancer should routinely be referred to ultraspecialist centers that are capable of performing advanced upper abdominal surgery. In reality, the great majority of patients with ovarian cancer in the United States have been and will be treated in community settings for the foreseeable future. The professional societies that represent gynecologic oncology have for years strongly recommended that ovarian cancer be handled by fellowship-trained gynecologic oncologists. This effort has met with mixed success; in many communities it is still the norm for women with advanced ovarian cancer to be operated on by physicians with no special oncologic surgical training.......

plus references:

REFERENCES

paywalled: Data for cancer comparative effectiveness research - Meyer - 2012 - Cancer - Wiley Online Library



Data for cancer comparative effectiveness research

Abstract

Comparative effectiveness research (CER) can efficiently and rapidly generate new scientific evidence and address knowledge gaps, reduce clinical uncertainty, and guide health care choices. Much of the potential in CER is driven by the application of novel methods to analyze existing data. Despite its potential, several challenges must be identified and overcome so that CER may be improved, accelerated, and expeditiously implemented into the broad spectrum of cancer care and clinical practice. To identify and characterize the challenges to cancer CER, the authors reviewed the literature and conducted semistructured interviews with 41 cancer CER researchers at the Agency for Healthcare Research and Quality's Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Cancer CER Consortium. Several data sets for cancer CER were identified and differentiated into an ontology of 8 categories and were characterized in terms of strengths, weaknesses, and utility. Several themes emerged during the development of this ontology and discussions with CER researchers. Dominant among them was accelerating cancer CER and promoting the acceptance of findings, which will necessitate transcending disciplinary silos to incorporate diverse perspectives and expertise. Multidisciplinary collaboration is required, including those with expertise in nonexperimental data, statistics, outcomes research, clinical trials, epidemiology, generalist and specialty medicine, survivorship, informatics, data, and methods, among others.

Recommendations highlight the systematic, collaborative identification of critical measures; application of more rigorous study design and sampling methods; policy-level resolution of issues in data ownership, governance, access, and cost; and development and application of consistent standards for data security, privacy, and confidentiality.

Tort Reform Arrives to Healthcare - Sue the Patient - Forbes



Tort Reform Arrives to Healthcare - Sue the Patient - Forbes

paywalled: Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness - European Journal of Cancer Care



Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness  - European Journal of Cancer Care 
 
Developing a useful, user-friendly website for cancer patient follow-up: users' perspectives on ease of access and usefulness
UK cancer survival has improved, leading to an increase in review patients and pressure on clinics......  Acceptability: Final evaluation (n= 103) was positive although many would like to maintain face-to-face hospital contact. User involvement in website design can ensure patient needs are met. A website model for follow-up will suit some patients but others will prefer clinical contact.

paywalled: First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG



 Epirubicin (Brand name: Ellence)

                     ~~~~~~~~~~~~~~~~~~~~~

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel.

Conclusion: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer. 

Thursday, April 26, 2012

paywalled: Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort - Gierach - 2011 - International Journal of Cancer - Wiley Online Library



Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort  - International Journal of Cancer 

"These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis."

UK: Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]



Advanced Solid Tumours Clinical Trial: Phase I Study of AT13148, a Novel AGC Kinase Inhibitor [Conditions: Advanced Solid Tumours; Interventions: AT13148]



The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours...

Brief Summary

Official Title: “A Cancer Research UK Phase I First in Man Study of the Novel AGC Kinase Inhibitor AT13148 Given Orally in Patients With Advanced Solid Tumours.”

The purpose of this first clinical study of the noval multiple AGC kinase inhibitor, AT13148, is to identify the recommended dose for future studies in cancer patients by exploring the safety and maximum tolerated dose and biological effects in patients with advanced solid tumours.
  • Study Type: Interventional
  • Study Design: Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: October 2015

Detailed Clinical Trial Description

AT13148 is a new drug which looks promising in laboratory studies. We now wish to find out if it will be useful in treating patients with cancer. AT13148 is a type of drug called a protein kinase inhibitor. It blocks several different chemical messengers (enzymes) called AGC kinase proteins. These chemical messengers are part of the signaling process within cells which can make cells produce chemicals that trigger and control cell growth and cell death. In some types of cancer these chemical messengers are 'switched on' or 'switched off' permanently due to changes in the genes of cells called "gene mutations" leading to uncontrolled cancer cell growth. AT13148 targets multiple protein kinases from three families of kinases unlike many of the other protein kinase inhibitors currently being tested which target just one or two kinases. This may mean that it will work better and in a wider group of cancer patients. Patients will not be selected to take part based on having these gene mutations for this first trial because we want to learn more about which mutations are most important but this would be the hope for future trials. The patient population anticipated to benefit from this drug includes certain types of breast, prostate and ovarian cancer which more commonly have these gene mutations.

26 APR 2012 - Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians - Wiley Online Library



Nutrition and physical activity guidelines for cancer survivors - CA: A Cancer Journal for Clinicians 

".... After receiving a diagnosis of cancer, survivors soon find there are few clear answers to even the simplest questions, such as: Should I change what I eat? Should I exercise more? Should I gain or lose weight? Should I take dietary supplements? Cancer survivors receive a wide range of advice from many sources about foods they should eat, foods they should avoid, how they should exercise, and what types of supplements they should take, if any. Unfortunately, this advice is often inconsistent and not supported by data...."


Ovarian Cancer

Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States.4 Symptoms tend be nonspecific, making early detection difficult. Consequently, most ovarian cancers are diagnosed at an advanced stage when the prognosis is poor, with an overall 10-year survival rate of 39%.4 The role of lifestyle factors in ovarian cancer prognosis is largely unknown.138, 242 To our knowledge, only 3 studies139, 140, 243 have evaluated the role of dietary factors in ovarian cancer survival. These 3 studies were based on prospective follow-up of the cases participating in case-control studies and evaluated the association between prediagnosis dietary intake and mortality outcomes. One study, conducted in China, focused on the role of green tea and reported that a higher frequency and quantity of green tea intake after diagnosis was associated with better survival.243 The other 2 studies, conducted in Australia140 and the United States,139 suggested that prediagnosis dietary intake may influence the survival experience of patients with ovarian cancer. Both studies tended to support the association of fruit and vegetable consumption with better survival. Dairy food intake was associated with poorer survival in one of the studies,140 while in the other, only milk consumption and not total dairy food consumption was inversely associated with survival.139 Meat consumption was associated with better survival in the Australian study,140 and with lower survival in the study conducted in the United States.139 While these studies controlled for most relevant covariates, they did not include treatment information. In addition, these studies did not evaluate dietary intake after diagnosis. However, they do suggest that dietary intake may influence ovarian cancer survival and warrant further research in this area.
Only one study, also following cases in a case-control study for mortality, has evaluated the role of physical activity in ovarian cancer survival.244 Prediagnosis physical activity was ascertained as hours per week for 3 life periods (childhood, between ages 18-30 years, and in recent years). The study also evaluated the role of changes in physical activity over time. There was not much indication of an association with survival for any of these variables, except for physical activity at aged 18 to 30 years, which seemed to be associated with better survival for women with early stage ovarian cancer and with worse survival for women with an advanced stage of disease at diagnosis.245
The relationship between excess weight and ovarian cancer survival has been evaluated by relatively few studies. Obesity may affect ovarian cancer survival by having a negative impact on optimal surgical and cytotoxic treatment and increasing the likelihood of postoperative complications.246 Overall, the literature evaluating the association between weight/BMI and ovarian cancer survival is limited and inconclusive.76, 242 Cohort studies evaluating the role of prediagnosis obesity obtained at baseline on ovarian cancer mortality have generally found elevated ovarian cancer mortality among obese women.234, 247 Other studies evaluating the role of prediagnosis BMI on ovarian cancer survival by following cases in a case-control study or clinical trial (using baseline data) have offered conflicting results.242 The role of postdiagnosis body size and weight changes on ovarian cancer survival is largely unknown. Only one study has reported on weight changes during chemotherapy and ovarian cancer survival and found that, among patients with advanced ovarian cancer, weight loss during chemotherapy was associated with worse prognosis; however, it is difficult to determine whether this weight loss was involuntary or intentional.248
In summary, while the current evidence is limited and inconclusive, it points to a possible role of dietary factors, physical activity, and body size and weight changes in modulating ovarian cancer survival, and for physical activity in improving the quality of life among ovarian cancer survivors. Further studies are needed before public health recommendations can be made.

paywalled: Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis



Blogger's Note/Opinion: as per abstract, to date and studies over decades, have not found a link between coffee/tea/ovarian cancer risk - so, the question is this: how many more studies will it take to finally put this issue to rest? Unless there are novel (new) findings then we need to move forward.

Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis

Abstract

Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). 

Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. 

Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. 

Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% CI: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. 

Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer.

paywalled: Systematic review of progesterone use by midlife and menopausal women



Systematic review of progesterone use by midlife and menopausal women: Publication year: 2012

Source: Maturitas

 Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception. Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.

Seth's Blog: Don't expect applause



Don't expect applause:

Accept applause, sure, please do.

But when you expect applause, when you do your work in order (and because of) applause, you have sold yourself short. That's because your work is depending on something out of your control. You have given away part of your art. If your work is filled with the hope and longing for applause, it's no longer your work--the dependence on approval has corrupted it, turned it into a process where you are striving for ever more approval.

Who decides if your work is good? When you are at your best, you do. If the work doesn't deliver on its purpose, if the pot you made leaks or the hammer you forged breaks, then you should learn to make a better one. But we don't blame the nail for breaking the hammer or the water for leaking from the pot. They are part of the system, just as the market embracing your product is part of marketing.

"Here, here it is, it's finished."

If it's finished, the applause, the thanks, the gratitude are something else. Something extra and not part of what you created. To play a beautiful song for two people or a thousand is the same song, and the amount of thanks you receive isn't part of that song.

medical news: Study confirms overuse of blood transfusions during surgery



Study confirms overuse of blood transfusions during surgery


"Citing the lack of clear guidelines for ordering blood transfusions during surgery, Johns Hopkins researchers say a new study confirms there is still wide variation in the use of transfusions and frequent use of transfused blood in patients who don't need it.
The resulting overuse of blood is problematic, the researchers say, because blood is a scarce and expensive resource and because recent studies have shown that surgical patients do no better, and may do worse, if given transfusions prematurely or unnecessarily. "Transfusion is not as safe as people think," says Steven M. Frank, M.D., leader of the study described in the journal Anesthesiology.....

Correspondence: Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM



Blogger's Note:  correspondence/author's reply/references; while this is specific to Avastin/breast cancer,  future trial protocols may take note

Bevacizumab in Neoadjuvant Treatment for Breast Cancer — NEJM

PLoS ONE: Effect of Angiogenesis Inhibitor (Avastin) Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature



 Blogger's Note: indicates which cancer patients did/did not show PFS/OS; limited to combo therapies (lack of monotherapy trials); read limitations to the analysis (eg. individual patient data/meta-analysis...); notes serious side effects

PLoS ONE: Effect of Angiogenesis Inhibitor Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature

paywalled: Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.



Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.


Abstract

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.

open access: Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review



Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review

Obstetrics and Gynecology International
Volume 2012 (2012), Article ID 953937, 11 pages
doi:10.1155/2012/953937 Review Article Cancer, Fertility Preservation, and Future Pregnancy: A Comprehensive Review

  • Abstract
  • Introduction
  • Methods and Materials
  • Results and Discussion
  • Options for Fertility Preservation
  • Additional Considerations
  • Pregnancy after Cancer

Conclusions 

Given the relatively high incidence of cancer in reproductive age women and improvements in 5-year survival, an increasing number of women are presenting for discussion of fertility preservation and pregnancy after cancer treatment. The ASCO published recommendations in 2006 on fertility preservation in cancer patients. These guidelines state that oncologists should address the possibility of infertility with cancer patients and be prepared to discuss possible fertility preservation options or refer the patient to a reproductive specialist. Part of the difficulty in counseling patients regarding the risk of infertility and/or subsequent pregnancy complications is that the risks are dependent on several factors. These risks include the dose and duration of treatment, other risk factors for infertility, the age of the patient, and the patient’s baseline ovarian reserve at the time of initiation of treatment.

paywalled: Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.





Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.

Breast Cancer Res Treat. 2012 Apr 18;

Abstract
The genetic component of breast cancer predisposition remains largely unexplained. Candidate gene case-control resequencing has identified predisposition genes characterised by rare, protein truncating mutations that confer moderate risks of disease. In theory, exome sequencing should yield additional genes of this class. Here, we explore the feasibility and design considerations of this approach. We performed exome sequencing in 50 individuals with familial breast cancer, applying frequency and protein function filters to identify variants most likely to be pathogenic. We identified 867,378 variants that passed the call quality filters of which 1,296 variants passed the frequency and protein truncation filters. The median number of validated, rare, protein truncating variants was 10 in individuals with, and without, mutations in known genes. The functional candidacy of mutated genes was similar in both groups. Without prior knowledge, the known genes would not have been recognisable as breast cancer predisposition genes. Everyone carries multiple rare mutations that are plausibly related to disease. Exome sequencing in common conditions will therefore require intelligent sample and variant prioritisation strategies in large case-control studies to deliver robust genetic evidence of disease association.


blogger: Hospitals, Practice Administrators and Clinicians: You Gotta Learn to Love Patient Ratings – Health Affairs Blog



Hospitals, Practice Administrators and Clinicians: You Gotta Learn to Love Patient Ratings – Health Affairs Blog

paywalled: Breast-feeding and risk of epithelial ovarian cancer (clear cell/endometrioid)




Breast-feeding and risk of epithelial ovarian cancer

 Abstract

PURPOSE:

Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail.

METHODS:

Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS:

Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987).

CONCLUSIONS:

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

paywalled: Journal of Cancer Education: Knowledge of Reproductive System Cancers, Their Treatments and Side Effects (Canada)




Knowledge of Reproductive System Cancers, Their Treatments and Side Effects


 Abstract 


We explored, via an online questionnaire, knowledge of breast and reproductive system cancers in patients and non-patients who access the internet for information on these diseases. We compared that knowledge to the attention the diseases have received in medical research and on the Internet. Data were collected from 690 respondents (37 % male, 63 % female) about their knowledge of prevalence, lethality, treatments and side effects of testicular, prostate, breast, uterine, cervical and ovarian cancers. Most males, but only half of the female participants, were patients themselves. Although participants showed better knowledge of cancers specific to their own sex, both sexes felt familiar with breast cancer and less aware of other cancers. Women were as aware as men of side effects of treatments for male reproductive cancers. Sex differences in awareness appear to reflect different attitudes towards illness, bias toward females as caregivers, and the disproportionate media attention given to breast cancer.

Wednesday, April 25, 2012

open access: Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis (ovarian/GI tract cancers)





Cell–cell and cell–matrix dynamics in intraperitonealcancer metastasis

 Abstract/pdf full text:

IntroductionIntraperitoneal dissemination is the primary metastatic route
of ovarian cancers. It is also a common progression for
gastrointestinal malignancies including colorectal, gastric,
and pancreatic cancers.....
                              ~~~~~~~~~~~~~~~~~

The peritoneal metastatic route of cancer dissemination
is shared by cancers of the ovary and gastrointestinal
tract.
Once initiated, peritoneal metastasis typically proceeds
rapidly in a feed-forward manner. Several factors
contribute to this efficient progression. In peritoneal metastasis,
cancer cells exfoliate into the peritoneal fluid and
spread locally, transported by peritoneal fluid. Inflammatory
cytokines released by tumor and immune cells compromise
the protective, anti-adhesive mesothelial cell layer that lines
the peritoneal cavity, exposing the underlying extracellular
matrix to which cancer cells readily attach. The peritoneum
is further rendered receptive to metastatic implantation and
growth by myofibroblastic cell behaviors also stimulated by
inflammatory cytokines. Individual cancer cells suspended
in peritoneal fluid can aggregate to form multicellular spheroids.

paywalled: Emergency department visits for symptoms experienced by oncology patients: a systematic review



Emergency department visits for symptoms... [Support Care Cancer. 2012] - PubMed - NCBI

CONCLUSIONS:

Individuals with cancer present to emergency departments with a myriad of symptoms. Over half of emergency department visits resulted in hospital admissions. Few symptoms were defined adequately to compare data across studies, thereby revealing an important gap in cancer symptom reporting.

paywalled: Cancer Risks for Relatives of Patients With Serrated Polyposis : The American Journal of Gastroenterology + link to Johns Hopkins (further explanation/genetics)



Access : Cancer Risks for Relatives of Patients With Serrated Polyposis : The American Journal of Gastroenterology


CONCLUSIONS:
Our finding that relatives of serrated polyposis patients are at significantly increased risk of colorectal and pancreatic cancer adds to the accumulating evidence that serrated polyposis has an inherited component.

                                ~~~~~~~~~~~~~~~~~
 Johns Hopkins Colon Cancer Center:


Individuals are diagnosed with hyperplastic polyposis when they have multiple hyperplastic polyps, usually greater than 20 polyps.  The number of polyps ranges anywhere from 6 to greater than 100, though most individuals with hyperplastic polyposis have between 40 and 100 polyps.  A diagnosis of Hyperplastic polyposis may also made in individuals who present with fewer than 20 hyperplastic polyps, but whose polyps are larger, often greater than 2 centimeters.  Individuals may also be diagnosed with multiple serrated adenomas or a mix of both serrated adenomas and hyperplastic polyps.  Hyperplastic polyposis is usually diagnosed in individuals in their 40’s to 60’s, though it has been reported in individuals as young as 11 years old.  Individuals with hyperplastic polyposis are at an increased risk for developing colorectal cancer, so routine screening is extremely important.  Although the genetic basis for FAP, HNPCC, Peutz-Jeghers, MYH-Associated Polyposis, and juvenile polyposis has been identified, hyperplastic polyposis has not yet been explained. Hyperplastic polyposis is suspected to have a familial basis and reports have shown that is inheritable in 5% of cases, though the exact mechanism of inheritance has not been identified.   

Supplements and cancer prevention: A cautionary tale - Journal of National Cancer Institute - press release



Supplements and cancer prevention: A cautionary tale

Public release date: 25-Apr-2012
Journal of the National Cancer Institute

Supplements and cancer prevention: A cautionary tale

Government regulators and the scientific community should work to ensure that they give clear guidance to the public about dietary supplements and cancer risk, according to a commentary published April 25 in the Journal of the National Cancer Institute.

Evidence from animal, in vitro and observational studies has suggested that taking dietary supplements may lower cancer risk. However, the small number of randomized controlled studies, the gold standard in evidence-based medicine, has not confirmed this—and some studies have actually shown that supplements may increase cancer risk. Still, the supplement industry is booming, with estimated annual sales at $30 billion in the U.S.

To examine the potential role of dietary supplements and cancer risk, Maria Elena Martinez, Ph.D., of the University of California San Diego Moores Cancer Center and colleagues, looked at observational studies of several supplements, including anti-oxidants, folic acid, vitamin D, and calcium. Several observational studies found that diets high in fruits and vegetables were associated with lower risk of certain cancers, including respiratory and gastrointestinal. Specifically, with respect to anti-oxidant supplements, the authors found that: "The importance of oxidative stress for carcinogenesis does not establish that the administration of supplemental antioxidants will protect against the carcinogenesis that oxidative stress may induce." Furthermore, they write, "Supplementation by exogenous antioxidants may well be a two-edged sword; these compounds could, in vivo, serve as pro-oxidants or interfere with any of a number of protective processes such as apoptosis induction." Indeed, several antioxidant trials the researchers examined reported increased cancer risks with supplementation. They looked at trials with supplements using folic acid, vitamin D and calcium, among other compounds.

The researchers caution against taking dietary supplements for cancer prevention, adding that many expert committees and organizations have concluded that nutritional supplements have little or no benefit in cancer prevention. They say that more randomized control trials—spanning many years instead of just a few—are needed to verify the effect of nutritional supplementation in cancer risk. 

Meanwhile, people continue to take supplements, spurred by manufacturers' suggestions that supplements are healthy at best and harmless at worst. Furthermore, believers in supplements assume that they are well regulated, the authors write. "These beliefs underscore the need for efforts by scientists and government officials to encourage the public to make prudent decisions based on sound evidence with respect to use of dietary supplements for cancer prevention."

Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine



Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine


(from Reuters) "....Dr. Aghajanian and colleagues note that overall survival data from the trial are not yet available; information on clinicaltrials.gov indicates a predicted study completion date of October 2013.
For now, say the researchers, "The data from OCEANS demonstrate that the addition of BV (bevacizumab) to GC (gemcitabine and carboplatin) can improve outcomes, and ongoing studies will assess whether this ability to add benefit is universal to other platinum-based combinations."
OCEANS is supported by Genentech, which markets bevacizumab as Avastin.

Patient-Centered Outcomes Research Institute Amends Draft Research Agenda in Response to Public Comment -- WASHINGTON, April 25, 2012 /PRNewswire-USNewswire/ --



Patient-Centered Outcomes Research Institute Amends Draft Research Agenda in Response to Public Comment -- WASHINGTON, April 25, 2012 /PRNewswire-USNewswire/ --

".....After discussion, the Board voted to make important changes to the Research Agenda. These include clarification of PCORI's focus on patient engagement and transparency; on patients with multiple chronic conditions; on patients with rare diseases; on improving health care systems, including care coordination, access to care, and the role of practice settings and allied health professionals; and on the importance of health literacy.
"The comments we received did not identify major gaps in the National Priorities, and there were no suggestions for additional priorities," said PCORI Executive Director Joe Selby, M.D., MPH. "This indicates that our priorities effectively capture the broad areas where more research is needed. Once the revised National Priorities and Research Agenda are approved, we will issue PCORI's first primary research funding announcements, which will emphasize the inclusion of patients and caregivers at all stages of the research."
PCORI reiterated its commitment to being a learning organization that will continually work with patients and stakeholders to revise its priorities and agenda as needed to address patients' evolving needs....."

open access: What Is the Heart of Health Care? Advocating for and Defining the Clinical Relationship in Patient-Centered Care | Journal of Participatory Medicine



What Is the Heart of Health Care? Advocating for and Defining the Clinical Relationship in Patient-Centered Care | Journal of Participatory Medicine

open access: Oxaliplatin-related thrombocytopenia



Oxaliplatin-related thrombocytopenia

Abstract/Full Text:

Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70 % of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia. 

conclusions

Oxaliplatin-related thrombocytopenia can prevent the administration of the optimal dose and schedule of this important chemotherapy agent and limit its benefits in the adjuvant or metastatic setting. Mild to moderate bone marrow suppression is the main cause of thrombocytopenia during and after treatment with oxaliplatin. In this setting, patients present thrombocytopenia concomitant to anemia and neutropenia usually 1–2 weeks after treatment. Therapeutic approaches will include dose delays or reduction and consideration of platelet-stimulating agents. However, novel mechanisms of oxaliplatin-related thrombocytopenia should promptly be recognized by physicians and include an immune-dependent mechanism, as well as portal hypertension related to sinusoidal injury yielding splenic sequestration of platelets.
OIIT usually presents a sudden and isolated drop in platelet counts minutes to hours after oxaliplatin administration, leading to acute hemorrhagic events. Female patients with advanced CRC and prior oxaliplatin exposure are more likely to develop this consequence. Prompt immunological testing documenting oxaliplatin-mediated platelet destruction leads to definitive diagnosis. Platelets counts will improve after discontinuation of treatment and transfusions may be necessary during the acute phase. Other measures such as corticoid or immunoglobulin administration are controversial and patients with documented OIIT should not be rechallenged with oxaliplatin.
Hepatic sinusoidal injury is a well-known complication of oxaliplatin treatment and can lead to portal hypertension and hypersplenism. Thrombocytopenia in this setting demonstrates a different natural history, with moderate but prolonged reductions in platelet counts. Splenomegaly and other complications of portal hypertension are recognized in these patients. Platelet recovery is slow and usually takes 2–3 years to be complete after treatment discontinuation. When a fast platelet recovery is wanted, splenic embolization might be considered as a therapeutic measure.
An improvement in the recognition of these mechanisms of oxaliplatin-related thrombocytopenia will permit a better documentation of them and help to understand possible risk factors associated with this complication in different settings. This information may help the development of new preventive and therapeutic approaches and allow for a more rational management of cancer patients treated with oxaliplatin that present thrombocytopenia.


paywalled: Japanese Journal of Clinical Oncology- LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis



LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis:

Objective
Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is an important novel gene associated with the proliferation and differentiation of cells. Recent studies have shown that it was overexpressed in many cancer tissues. This study investigated the association between different LAPTM4B polymorphisms and the susceptibility and prognosis of ovarian cancer.

Methods
A case–control study was performed in 282 patients with ovarian cancer and 365 control subjects. Genomic DNA was extracted from peripheral blood lymphocytes in all participants. LAPTM4B genotypes were determined using polymerase chain reaction.

Results
There was a significantly higher LAPTM4B*2 allele frequency in ovarian cancer cases than controls (P < 0.05). Using the LAPTM4B*1/1 genotype as the reference, we found that the LAPTM4B*1/2 and LAPTM4B*2/2 genotypes were positively associated with ovarian cancer.

Current Drug Shortages: Paclitaxel Injection (updated)



Current Drug Shortages: Paclitaxel Injection (updated):

APP is currently back-ordered on 100 mg/16.7 mL vial (NDC 63323-0763-16) and 300 mg/50 mL vial (NDC 63323-0763-50). 30 mg/5 mL vial (NDC 63323-0763-05) is currently available.

Current Drug Shortages: Ondansetron Injection 2 mg/mL (updated)



Current Drug Shortages: Ondansetron Injection 2 mg/mL (updated):

APP has Ondansetron 2 mg/mL 2 mL vials on back order with an estimated release date of early May 2012. Check wholesalers for inventory. The 40 mg, 20mL vials are on back-order until late May.

paywalled: Jpn. J. Clin. Oncol. (2012) - Oncology Information on the Internet



Oncology Information on the Internet

Abstract:

Owing to new developments in Internet technologies, the amount of available oncology information is growing. Both patients and caregivers are increasingly using the Internet to obtain medical information. However, while it is easy to provide information, ensuring its quality is always a concern. Thus, many instruments for evaluating the quality of health information have been created, each with its own advantages and disadvantages. The increasing importance of online search engines such as Google warrants the examination of the correlation between their rankings and medical quality. The Internet also mediates the exchange of information from one individual to another. Mailing lists of advocate groups and social networking sites help spread information to patients and caregivers. While text messages are still the main medium of communication, audio and video messages are also increasing rapidly, accelerating the communication on the Internet. Future health information developments on the Internet include merging patients' personal information on the Internet with their traditional health records and facilitating the interaction among patients, caregivers and health-care providers. Through these developments, the Internet is expected to strengthen the mutually beneficial relationships among all stakeholders in the field of medicine.

paywalled: Clinical development of new formulations of cytotoxics in so... : Current Opinion in Oncology



Clinical development of new formulations of cytotoxics in so... : Current Opinion in Oncology

Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 325–331
doi: 10.1097/CCO.0b013e328351fb29
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada

Clinical development of new formulations of cytotoxics in solid tumors


Abstract

Purpose of review: 
To discuss the clinical development of new formulations of old cytotoxic agents and highlight the value of adopting this strategy.

Recent findings: 
Several drugs are currently in clinical development with high potential in improving clinical outcomes compared with their older counterparts. We emphasize on the results of four of these agents, each belonging to a known group of cytotoxics namely amrubicin, EndoTAG-1, pralatrexate and NKTR-102. Each has shown promising results that have the potential in addressing some limitations that have been observed with the ‘earlier generation’ agents.

Summary:  
Improvement in drug development strategies and the appreciation of the mechanisms of action and resistance of the cytotoxic agents currently available in the clinic open the door for developing agents that have the potential of improving clinical outcomes with better safety profiles. It is important to adopt innovative clinical trials designs integrating molecular markers in early clinical development in order to identify the subgroups of patients who would derive the maximal benefit of these novel agents.

paywalled: Targeting the DNA damage response in oncology: past, presen... : Current Opinion in Oncology



Targeting the DNA damage response in oncology: past, presen... : Current Opinion in Oncology

Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 316–324
doi: 10.1097/CCO.0b013e32835280c6
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada

Targeting the DNA damage response in oncology: past, present and future perspectives

Abstract

Purpose of review: 
The success of poly(ADP-ribose) polymerase inhibition in BRCA1 or BRCA2 deficient tumors as an anticancer strategy provided proof-of-concept for a synthetic lethality approach in oncology. There is therefore now active interest in expanding this approach to include other agents targeting the DNA damage response (DDR). We review lessons learnt from the development of inhibitors against DNA damage response mechanisms and envision the future of DNA repair inhibition in oncology.

paywalled: Vascular disrupting agents: a delicate balance between efficacy and side (safety) effects



Vascular disrupting agents: a delicate balance between effi... : Current Opinion in Oncology

Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 305–315
doi: 10.1097/CCO.0b013e32835249de
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada

Abstract

Purpose of review: 
Targeting the tumor vasculature is an attractive approach for cancer therapy. Vascular disrupting agents (VDAs) are compounds that directly target tumor blood vessels and create central tumor necrosis. The current review aims to summarize the clinical development (i.e. safety and efficacy) of this class of compounds.

Recent findings: 
VDAs have demonstrated signs of clinical activity in different tumor types [e.g. anaplastic thyroid carcinoma (ATC), nonsmall cell lung carcinoma (NSCLC), ovarian cancer, sarcoma]. However, the lack of predictive biomarkers to identify patients with a high probability of response to VDAs, places this class of compounds at a high risk of failure. This has recently been exemplified by several negative phase II/III trials in NSCLC, ATC, and castration-refractory metastatic prostate cancer.

Summary: 
VDAs represent a unique class of anticancer compounds. Their clinical development is hampered by cardiovascular, neurological toxicities as single agent and by hematological toxicity in combination with chemotherapy. Molecular predictors of their efficacy are crucial for further development. As single agent, only few objective responses have been observed in a variety of solid tumors. However, VDAs have failed to demonstrate a survival advantage in several phase II/III trials especially in combination with chemotherapy.

7 steps to managing angry (hostile) patients - Staff members are central to this proven technique - ModernMedicine



7 steps to managing angry patients - Staff members are central to this proven technique - ModernMedicine

paywalled: ncreased risk of neoplasm in appendicitis treated w... [Am Surg. 2012] - PubMed - NCBI



Increased risk of neoplasm in appendicitis treated w... [Am Surg. 2012] - PubMed - NCBI

Am Surg. 2012 Mar;78(3):339-43.

Increased risk of neoplasm in appendicitis treated with interval appendectomy: single-institution experience and literature

Abstract

Appendicitis is a common diagnosis encountered by the acute care surgeon. Management of complicated appendicitis is controversial and often involves initial nonoperative therapy with interval appendectomy. This study reviews single-institutional experience with management of complicated appendicitis with interval appendectomy and addresses an unusually high occurrence of incidental appendiceal malignancies observed with a review of relevant literature. A retrospective review of all diagnoses of appendicitis was performed over 5 years at a tertiary care center. Patient demographics, time to surgery, operative technique, pathologic diagnosis, and clinical outcomes were examined. Three hundred fifteen patients were diagnosed with acute appendicitis. Of these, 24 (7.6%) were deemed complicated and did not undergo immediate appendectomy, and 18 ultimately underwent appendectomy at our institution and were included in analysis. There were no statistical demographic or symptomatic differences between the immediate and interval appendectomy patients. Ninety-nine per cent of the immediate appendectomy patients were treated laparoscopically; 78 per cent of the interval group underwent attempted laparoscopic treatment with 56 per cent completed without conversion to open (P < 0.01). Neoplasms were discovered in 1 per cent of the acute appendectomy group and 28 per cent of the interval appendectomy group (P < 0.0001). Two of the three neoplasms in the acute group were carcinoid, whereas three of the five neoplasms in the interval group were adenocarcinoma. Surgeons should consider appendiceal or colonic neoplasms in cases of complicated appendicitis when nonoperative management is considered. This is most important in patients older than 40 years, in those who forego interval appendectomy, or in those who could be lost to follow-up.

2012 ASCO Annual Meeting | Abstracts to be released online May 16th



2012 ASCO Annual Meeting | Abstracts

 May 16 at 6:00 PM (EDT) Abstracts released on ASCO.org*

paywalled: Breast cancer metastasising to the pelvis and abdomen: what the gynaecologist needs to know - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library



Breast cancer metastasising to the pelvis and abdomen: what the gynaecologist needs to know - Moore - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library


A small proportion of breast cancers metastasize within the peritoneal cavity. With increasing breast cancer incidence rates, gynaecologists and oncologists will encounter such women more frequently. Most women with intraperitoneal breast cancer are premenopausal. Although data are limited and are likely to be subject to selection bias, the median survival of women undergoing resection appears superior to those not undergoing surgery. Furthermore, survival is broadly similar to that for women undergoing advanced ovarian cancer surgery, particularly when tumour debulking is optimal. Obtaining data via randomised trials is unlikely to be feasible and therefore we recommend prospective data collection via the establishment of an international intraperitoneal breast cancer patient registry. For individual women where survival is anticipated to be more than a few months, we suggest considering referral to a gynaecological oncology team for discussion of surgical options.

future postings - term 'subscription required' replaced by 'paywalled'



Blogger's Note: wording/term change - 'paywalled' (new) = subscription required ($$$) (old), plain english - blog postings of the future which indicate the term 'paywalled' means that access to the article requires a paid subscription

abstract: Topoisomerase 1 Inhibitors and Cancer Therapy



 Blogger's Note: to view full paper, subscription ($$$) required

Topoisomerase 1 Inhibitors and Cancer Therapy

 Abstract: "Topoisomerase 1 inhibitors cure human cancer xenografts in animal models, more so than most other chemotherapy agents. However, their activity in patients with cancer is modest. Ongoing research is studying the optimal analogues that could reproduce animal data in the cancer population. This article analyzes the clinical research with topoisomerase 1 inhibitors in ovarian cancer."

Harvard Libraries join the fight for open access - science blog



Harvard Libraries join the fight for open access

financial: Amgen - Media - Press Release (Product Sales Performance eg. Neupogen/Etanercept/Darbepoetin/Aranesp/Epogen...)



Amgen - Media - Press Release

Product Sales Performance
 

XGEVA® (denosumab) sales were $153 million in the first quarter of 2012, an increase of 14 percent over the fourth quarter of 2011, reflecting increased segment share as well as overall segment growth.

Prolia® (denosumab) sales were $88 million in the first quarter of 2012, an increase of 9 percent over the fourth quarter of 2011, reflecting continued global growth.

Combined Neulasta® (pegfilgrastim) and NEUPOGEN® (Filgrastim) sales increased 9 percent to $1,344 million in the first quarter of 2012 versus $1,232 million in the first quarter of 2011. Combined U.S. Neulasta and NEUPOGEN sales increased 13 percent to $1,053 million in the first quarter of 2012 versus $930 million in the first quarter of 2011, driven primarily by an increase in the average net sales price and, to a lesser extent, an increase in Neulasta unit demand. Combined Neulasta and NEUPOGEN international sales decreased 4 percent to $291 million in the first quarter of 2012 versus $302 million in the first quarter of 2011, due primarily to a decrease in the average net sales price. A mid single-digit percentage point increase in Neulasta unit demand was offset by a decline in NEUPOGEN units due primarily to biosimilar competition.

Enbrel® (etanercept) sales increased 7 percent to $938 million in the first quarter of 2012 versus $875 million in the first quarter 2011, driven primarily by an increase in the average net sales price. ENBREL remains the segment share leader in both the rheumatology and dermatology segments.

Aranesp® (darbepoetin alfa) sales decreased 11 percent to $518 million in the first quarter of 2012 versus $580 million in the first quarter of 2011. U.S. Aranesp sales decreased 19 percent to $202 million in the first quarter of 2012 versus $250 million in the first quarter of 2011, due primarily to a decline in unit demand, offset partially by a mid single-digit percentage point increase in the average net sales price. The unit decline reflects segment contraction resulting from changes to the product label and reimbursement environment that occurred during 2011. International Aranesp sales decreased 4 percent to $316 million in the first quarter of 2012 versus $330 million in the first quarter of 2011, due primarily to a decrease in the average net sales price.

EPOGEN® (epoetin alfa) sales decreased 17 percent to $446 million in the first quarter of 2012 versus $535 million in the first quarter of 2011, reflecting the impact of changes to the label and reimbursement. The decline was comprised of an approximately 30 percent decrease in unit demand driven by a reduction in dose utilization, offset partially by reductions in customer discounts as part of new provider contracts that became effective Jan. 1, 2012.

On a sequential basis, EPOGEN sales decreased 8 percent, comprised of an approximately 20 percent decrease in unit demand driven by the timing of end-user purchases at the end of 2011 and a reduction in dose utilization. These decreases were offset partially by reductions in customer discounts as part of new provider contracts.
Sales of our other, growth-phase products increased 22 percent to $399 million in the first quarter 2012 versus $327 million in the first quarter of 2011. Sales of Sensipar®/Mimpara® (cinacalcet) increased 17 percent to $219 million in the first quarter of 2012 versus $187 million in the first quarter of 2011. Sales of Vectibix® (panitumumab) increased 20 percent to $90 million in the first quarter of 2012 versus $75 million in the first quarter of 2011. Sales of Nplate® (romiplostim) increased 38 percent to $90 million in the first quarter of 2012 versus $65 million in the first quarter of 2011. These increases were driven primarily by global unit growth.