PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma

Abstract

Dysregulated signaling on the PI3-kinase/Akt cascade is reportedly associated with early stage and favorable prognosis in some kinds of malignancies including breast cancer, endometrial cancer, and colorectal cancer. PIK3CA, a catalytic subunit of PI3-kinase, is known to be activated in ovarian clear cell carcinoma (CCC), which is categorized as type I ovarian cancer. The aim of this study was to investigate the clinical significance of PIK3CA overexpression in the disease. We performed immunohistochemical analyses of PIK3CA, PTEN, p-Akt, p27 and p53 expressions in primary ovarian clear cell carcinomas from 62 Japanese patients. Genetic analyses of PIK3CA mutation and amplification were further conducted. PIK3CA was overexpressed in 45 tumors (73%), PTEN expression was negative in 3 (5%), and p53 was positive in 8 (13%). Overexpressed PIK3CA was found to be associated with p-Akt overexpression (P = .007). PIK3CA overexpression tended to be observed in more of stage I disease (73% versus 47%, P = .07) and was associated with absence of residual tumor at the initial surgery (96% versus 71%, P = .01). Furthermore, survival analyses revealed that PIK3CA overexpression correlated with improved overall survival (P = .03). Subsequent genetic analyses demonstrated that PIK3CA overexpression correlated with the presence of mutation or amplification of the PIK3CA gene in tumors (P = .009). Our observations suggest that the subgroup of ovarian clear cell carcinomas harboring activated PIK3CA seems to have better prognosis possibly due to more indolent biological property compared to tumors without PIK3CA activation. PIK3CA may serve as a biomarker for good prognosis and a possible therapeutic target in this lethal subtype of ovarian cancer.

TIME's "How To Cure Cancer" cover - worst of the year?

TIME's "How To Cure Cancer" cover -

Posted by Gary Schwitzer in Cancer, Health care journalism

1 Comment

That’s what journalist Seth Mnookin writes on Slate, stating, further, that it is “is wrong, grandiose, and cruel.”
He writes, “I haven’t found a single cancer researcher who believes this means we’re on the verge of curing cancer.”.....

(things you don't know) Robotic surgery tied to temporary nerve injuries | Reuters

Reuters

NEW YORK | Fri Mar 29, 2013 2:03pm EDT

(Reuters Health) - One in 15 people undergoing robot-assisted prostate, kidney or bladder surgery develops a nerve injury related to pressure from positioning on the operating table, a new study suggests.
Patients on the table getting those types of robotic surgery need to be tilted steeply - with their head by the floor and their feet in the air - to give the surgeon better traction, researchers explained.

 

"When somebody is in that position, there's a chance they could slide down - it's like a big ramp," said lead author Dr. Tracey Krupski, from the University of Virginia School of Medicine in Charlottesville.....

Author of new breast cancer study (WHI/HRT) comments on its findings of increased risk

media

LA Biomed researcher studied the effects of combined hormone therapy

Dr. Rowan Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute lead researcher and author of a study released March 29 by the Journal of the National Cancer Institute, issued the following statement regarding the latest findings from the Women's Health Initiative, the largest-ever study of hormonal therapy in post-menopausal women.
The study Dr. Chlebowski authored reported that estrogen plus progestin use is linked with increased breast cancer incidence. In addition, it said the prognosis is similar for both users and nonusers of combined hormone therapy, suggesting that mortality from breast cancer may be higher for hormone therapy users as well.
"This study shows that women who begin the hormonal therapy of estrogen plus progestin closer to menopause are at greater risk of breast cancer than those who started the therapy earlier. Because menopause usually is the reason for women to undergo hormonal therapy, this is a very significant finding.
"The study also showed that all categories of breast cancer are increased - not just those with favorable prognosis - among women using estrogen plus progestin. This finding suggests higher mortality from breast cancer among women who use this combined hormonal therapy. As always, women should consult with their physicians and consider the potential risks of any hormonal therapy to help relieve the symptoms of menopause."

###

About LA BioMed
Founded in 1952, LA BioMed is one of the country's leading nonprofit independent biomedical research institutes. It has approximately 100 principal researchers conducting studies into improved treatments and cures for cancer, inherited diseases, infectious diseases, illnesses caused by environmental factors and more. It also educates young scientists and provides community services, including prenatal counseling and childhood nutrition programs. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA and located on the campus of Harbor-UCLA Medical Center. For more information, please visit http://www.LABioMed.org

---

Sorrento Therapeutics, Inc. and IGDRASOL Announce Three Presentations on Cynviloq™ (IG-001; paclitaxel polymeric micelle) at the (AACR) Meeting

press release

".....Sorrento Therapeutics, Inc. ("STI"; SRNE) and IGDRASOL announced today that IGDRASOL will be presenting updates of its development of Cynviloq™ (IG-001) at the annual meeting of the American Association for Cancer Research (AACR) in Washington, DC (April 6^th to 10^th).  IGDRASOL is a privately-held company for which STI was granted an irrevocable option right to acquire.  The two companies' combined pipeline features an oncology franchise of potential products with Phase 2 data for multiple solid tumor indications as well as two synergistic drug discovery and development platforms, namely the G-MAB® human antibody library and MABiT™, a proprietary technology to generate antibody formulated drug conjugates (AfDC).Cynviloq™ (or IG-001) is a next-generation, branded, micellar diblock copolymeric paclitaxel formulation currently approved and marketed in several countries as Genexol-PM®. Cynviloq™ has completed Phase 1 or 2 trials in MBC, NSCLC, pancreatic cancer, ovarian cancer and bladder cancer in the U.S. and/or non-U.S. IGDRASOL is preparing for an "End of Phase 2" meeting with the U.S. Food & Drug Administration (FDA) targeted for the first half of 2013 regarding Cynviloq™.  As an injectable nanoparticle formulation of paclitaxel, Cynviloq™ is potentially eligible for approval via FDA's 505(b)(2) bioequivalence regulatory pathway versus albumin-bound paclitaxel (nab-paclitaxel; Abraxane®) in its currently approved MBC and NSCLC indications..... 

(Italy)Clinical governance network for clinical audit to improve quality in epithelial ovarian cancer management

open access

Background
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Worldwide, there are 224,747 new cases yearly and an estimated 140,163 disease-related deaths [1]. In Europe, approximately 66,700 new ovarian cancer cases are diagnosed yearly, with the highest incidence in the Northern European countries and the United Kingdom [2,3]. The lifetime risk varies from 1.1 to 1.6 in Europe and the United States (US) [4]. The majority of women (about 65%) are diagnosed at advanced International Federation of Obstetricians and Gynecologists (FIGO) III-IV, 5-year survival is only 48.8% of all the patients, and the
median overall survival is 24 months. However, the 5-year-survival rate varies widely among European countries, from 25.6% to 51.4% [5,6].

Conclusions

The differences in terms of treatments provided led the multidisciplinary group to identify reference centers, to promote centralization, to ensure uniform and adequate treatment to patients treated in regional centers and to promote a new audit involving all regional hospitals to a complete review of the all the EOC patients. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. 

 ages/treatments of patients included in this study:

 Table 3  (age/treatments - including none) Characteristics of the 2163 EOC patients treated between 2007-2010

"Over the last decade, several studies have reported the importance of centralizing care of ovarian cancer patients to guarantee the assistance of specialized gynecologists, thereby improving prognosis/ survival [7-11]."

 

Screening Guidelines: Ovarian Cancer | Memorial Sloan-Kettering Cancer Center

Memorial Sloan-Kettering Cancer Center

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

Further information regarding screening and risk-reduction recommendations for women who are members of known hereditary cancer families are summarized in our Hereditary Cancer & Genetics section.

Patient Quality of Life Endpoints in Oncology Trials, Part I - Cancer Network

 Cancer Network

Hypersensitivity of the hippocampal CA3 region to stress-induced neurodegeneration and amyloidogenesis in a rat model of surgical menopause

Abstract

"Females who enter menopause prematurely via bilateral ovariectomy (surgical menopause) have a significantly increased risk for cognitive decline and dementia. To help elucidate the mechanisms underlying this phenomenon, we used an animal model of surgical menopause, long-term (10-week) bilateral ovariectomy in female rats. Herein, we demonstrate that long-term oestrogen deprivation dramatically increases sensitivity of the normally resistant hippocampal CA3 region to ischaemic stress, an effect that was gender-specific, as it was not observed in long-term orchiectomized males. Furthermore, the enhanced damage to the CA3 region correlated with a worse cognitive outcome after ischaemic stress. Long-term ovariectomized rats also displayed a robust hyperinduction of Alzheimer’s disease-related proteins in the CA3 region and a switch in amyloid precursor protein processing from non-amyloidogenic to amyloidogenic following ischaemic stress CA3 hypersensitivity also extended to an Alzheimer’s disease-relevant insult, as the CA3 region of long-term ovariectomized rats was profoundly hypersensitive to the neurotoxic effects of amyloid-β1–42, the most amyloidogenic form of the amyloid-β peptide. Additional studies revealed that CA3 region hypersensitivity, Alzheimer’s disease-related protein induction, and amyloidogenesis are mediated by a NADPH oxidase/superoxide/c-Jun N-terminal kinase/c-Jun signalling pathway, involving both transcriptional and post-translational mechanisms. In addition, while 17β-oestradiol replacement at the end of the long-term oestrogen deprivation period could not prevent CA3 hypersensitivity and amyloidogenesis, if 17β-oestradiol was initiated at the time of ovariectomy and maintained throughout the 10-week oestrogen deprivation period, it completely prevented these events, providing support for the ‘critical window’ hypothesis for oestrogen replacement therapy benefit. Collectively, these findings may help explain the increased risk of cognitive decline and dementia observed in women following surgical menopause, and they provide increased support that early 17β-oestradiol replacement is critical in preventing the negative neural effects associated with bilateral ovariectomy.

Surgical menopause may prime brain for stroke, Alzheimer's

press release

Women who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.

"This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up," said Brann, corresponding author of the study in the journal Brain. "We wanted to find out why that is occurring. We suspect it's due to the premature loss of estrogen."
In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.
When the researchers caused a stroke-like event in the brain's hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.
To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer's disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer's.
Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.
Interestingly the brain's increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn't affect stroke size or damage.
Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.
Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.
The surprising results of the much-publicized Women's Health Initiative – a 12-year study of 161,808 women ages 50-79 – found hormone therapy generally increased rather than decreased stroke risk as well as other health problems. Critics said one problem with the study was that many of the women, like Brann's aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.

###

The research was supported by the National Institute of Neurological Disorders and Stroke, an American Heart Association Scientist Development grant and a National Natural Science Foundation grant.

join the discussion: Greatest Challenge for Patient Empowerment | LinkedIn

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Join LinkedIn for free to participate in the conversation. When you join, you can comment and post your own discussions.

A. Maria

Greatest Challenge for Patient Empowerment

I would like to hear your thoughts on why patients have never been truly empowered to be their own best advocates. Is the issue a failure of the healthcare system to engage them in a manner that appeals to them or is it the lack of motivation to play an active role. Or, is it a little bit of both?

Sulforaphane Induces Cell Cycle Arrest, Migration, Invasion, and Apoptosis in Epithelial Ovarian Cancer Cells | Chuang | American Journal of Cancer Review

open access | American Journal of Cancer Review


Objectives: Isothiocyanates (ITC) has long been shown to demonstrate chemopreventive properties. Sulforaphane (SFN) is a major ITC present in broccoli and other cruciferous vegetables. We reviewed the current literatures of SFN on ovarian carcinoma cell lines.....

open access: The novel cancer-testis antigen A-kinase anchor protein 4 (AKAP4) is a potential target for immunotherapy of ovarian serous carcinoma

open access

"...The presence of circulating anti-AKAP4 antibodies suggests the AKAP4 is highly immunogenic in ovarian serous carcinoma patients. Our study lays the foundations for exploring AKAP4 as a potential target for the immunotherapy of ovarian cancer."

open access: Retroviral Interferon- α Gene Transfer Potentiates Paclitaxel against Ovarian Cancer Cells

open access/pdf

Abstract

Objective: To analyze the cytotoxic effects of paclitaxel following introduction of the retroviral interferon- α (IFN-
α) gene into epithelial ovarian cancer cells.

Design: Experimental molecular study.

Setting: University hospital research center. Sample: Epithelial ovarian cancer cell lines OV-2774 and SKOV3.
Empty vector was used as control.

Methods: The cytotoxic effects of paclitaxel on ovarian cancer cells were studied prior to and after transfection with the retrovirus-mediated inteferon- α gene. RT/PCR of the interferon gene, cell survival and cell death were analyzed to assess retroviral interferon- α gene expression after transfection.

Results: Paclitaxel inhibited cell growth in a dose dependent manner with half maximal inhibitory concentration
(IC50) of 7.5 ng/ml. Retroviral inteferon- α gene transfer-transduced cells potentiated paclitaxel response against both ovarian cancer cell lines by 68%.

Conclusion: Retrovirus-mediated IFN- α gene transfer enhanced paclitaxel cytotoxicity on ovarian cancer cells.
Retroviral IFN- α gene transfer in combination with paclitaxel may have significant clinical utility for the treatment of epithelial ovarian cancers.

Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients

Abstract

Purchase $31.50

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Highlights

•

Ovarian cancer (OvCa) is the most lethal gynecological malignancy.

•

No adequate screening or diagnostic tools exist for early stage OvCa diagnosis.

•

FOLR1 appears to be a promising novel (new) serological biomarker for ovarian cancer.

---

Objectives

Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women.

Design and methods

FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate.

Results

FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P < 0.0001) and patients with benign gynecological conditions (P < 0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125.

Conclusions

FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.

Diagnostics | Free Full-Text | MicroRNAs as Biomarkers in Cancer

Blogger's Note: discusses ovarian cancer/CA125....

Free Full-Text

open access: case reports: Pathology - Ovarian Serous Carcinoma Associated With a Distinct “Corded and Hyalinized” Pattern

Archives of Pathology & Laboratory Medicine Online

article/editorial/press: paywalled: Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

requires subscription

Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

1. Rowan T. Chlebowski,
2. JoAnn E. Manson,
3. Garnet L. Anderson,
4. Jane A. Cauley,
5. Aaron K. Aragaki,
6. Marcia L. Stefanick,
7. Dorothy S. Lane,
8. Karen C. Johnson,
9. Jean Wactawski-Wende,
10. Chu Chen,
11. Lihong Qi,
12. Shagufta Yasmeen,
13. Polly A. Newcomb and
14. Ross L. Prentice

+ Author Affiliations

1. Affiliation of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, CC, AKA, PAN); University of Pittsburgh, Pittsburgh, PA (JAC); Stanford University, Stanford, CA (MLS); State University of New York, Stony Brook, NY (DSL); University of Tennessee Health Science Center, Memphis, TN (KCJ); University at Buffalo, Buffalo, NY (JWW); University of California at Davis, Sacramento, CA (LQ, SY).

1. Correspondence to: Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson St, Torrance, CA, 90502 (e-mail: rowanchlebowski@gmail.com).

• Received August 27, 2012.
• Revision received January 20, 2013.
• Accepted February 13, 2013.

Abstract

Background In the Women’s Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.

Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.

Results After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.

Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.

• © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Related articles

Solicited Editorial:
• Catherine Schairer and
• Louise A. Brinton
The Effect of Estrogen Plus Progestin Hormone Therapy on Breast Cancer Mortality: Still Unresolved JNCI J Natl Cancer Inst first published online March 29, 2013 doi:10.1093/jnci/djt058
• Extract
• Full Text (HTML)
• Full Text (PDF)
Memo to the Media: Estrogen Plus Progestin Use Linked With Increased Breast Cancer Incidence and Mortality JNCI J Natl Cancer Inst first published online March 29, 2013 doi:10.1093/jnci/djt092
• Extract
• Full Text (HTML)
• Full Text (PDF)

The Effect of Estrogen Plus Progestin Hormone Therapy on Breast Cancer Mortality: Still Unresolved

extract 

+ Author Affiliations

1. Affiliation of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (CS, LAB).

1. Correspondence to: Catherine Schairer, PhD, National Cancer Institute, 6210 Executive Blvd, Room 8026, Rockville, MD 20852 (e-mail: schairec@exchange.nih.gov).

The article by Chlebowski et al. in this issue of the Journal (1) follows upon eight articles that have described the relationship between estrogen/progestin therapy and invasive breast cancer risk/mortality in studies from the Women’s Health Initiative (WHI) (2–9). Although a previous analysis addressed relationships between estrogen plus progestin use and breast cancer incidence among participants in the WHI Observational Study (WHIOS) (5), a cohort noted to have characteristics similar to participants in the WHI Randomized Trial (WHIRT), this is the first presentation of data from the WHIOS related to mortality outcomes. A major goal of the Chlebowski et al. study was to explore discrepancies between the randomized trial, which noted increased breast cancer mortality and adverse tumor characteristics associated with estrogen plus progestin therapy, and previous observational studies, which have mainly found usage to be associated with favorable prognosis breast cancers.

Findings about increased breast cancer incidence associated with estrogen plus progestin therapy from the WHIRT were first published in 2002 after a mean follow-up of 5.2 years (2). Tumor characteristics were reported after a mean follow-up of 5.6 years; with 199 observed breast cancers in the estrogen plus progestin group (3), the invasive breast cancers were larger, more likely …

[Full Text of this Article] ($$$)

Related articles

Article:
• Rowan T. Chlebowski,
• JoAnn E. Manson,
• Garnet L. Anderson,
• Jane A. Cauley,
• Aaron K. Aragaki,
• Marcia L. Stefanick,
• Dorothy S. Lane,
• Karen C. Johnson,
• Jean Wactawski-Wende,
• Chu Chen,
• Lihong Qi,
• Shagufta Yasmeen,
• Polly A. Newcomb,
• and Ross L. Prentice
Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study JNCI J Natl Cancer Inst first published online March 29, 2013 doi:10.1093/jnci/djt043
• Abstract
• Full Text (HTML)
• Full Text (PDF)
• Supplementary Data

Shortage of Cancer Drugs Pose Survival Risks to Patients

Medscape
The drugs most frequently reported to be in short supply are fluorouracil, leucovorin, liposomal doxorubicin, and paclitaxel. These shortages have the greatest effect on patients battling ovarian, breast, and colorectal cancers.....

Long Hours and Compassion Fatigue Stress Oncologists

Medscape

Measuring psychosocial outcomes: is the consumer or the professional the best judge?

open access

 Abstract

In this review, we explore professionally-driven and consumer-driven paradigms in measuring psychosocial outcomes for cancer care. Early measures of psychosocial well-being focussed on clinically-derived concepts of dysfunction. Recent literature reflects a paradigm shift toward a consumer-driven approach to the conceptualisation and measurement of psychosocial well-being. The key distinction between the two approaches rests on whether the professional or consumer retains judgement authority and raises the question of whether it is necessary to include both perspectives in research and practice. Research is proposed to clarify our interpretation of these approaches with a view to devising novel interventions to benefit patient well-being.......

" The impact of the problem
The biomedical model assumes that disease is an ‘undesirable deviation or discontinuity’ that ‘gives rise to the need for corrective actions’ (Engel 1977). This facilitates standardisation of diagnoses and therefore, choice of appropriate treatment regimes (Widiger & Samuel 2005). A professionally-driven approach to psychosocial measurement will as a result, focus on describing and quantifying recognised symptoms. For example, QoL measures such as the Functional Living Index for Cancer (FLIC) quantify the degree or frequency of a symptom without reference to whether that experience is of importance or value to the patient.......

Long-term results of weekly paclitaxel carboplatin induction therapy: An effective and well-tolerated treatment in patients with platinum-resistant ovarian cancer

Abstract

Abstract 

Background

Weekly paclitaxel/cisplatin is effective in platinum-resistant epithelial ovarian cancer (EOC). To reduce toxicity, paclitaxel/cisplatin was replaced by paclitaxel/carboplatin.

Patients and methods

Patients with progressive EOC after prior 3-weekly paclitaxel/carboplatin were treated with six cycles weekly paclitaxel 90mg/m² and carboplatin area under the curve (AUC) 4mg/ml/min, followed by six cycles 3-weekly paclitaxel/carboplatin. End-points were progression free survival (PFS), overall survival (OS), response rate (RR) and toxicity.

Results

Median progression free interval after last platinum was 9 (0–81) months in 108 patients; 43 were platinum-resistant, of whom 13 started weekly paclitaxel/carboplatin <6months after progression. During 633 weekly cycles grade 3/4 toxicity included; thrombocytopenia 8%, neutropenia 30%, febrile neutropenia 0.5%. Non-haematologic toxicity was low. Treatment was delayed in 16%, and dose reduced in 2% of cycles. RR was 58% for platinum-resistant and 76% for platinum-sensitive patients, median PFS were 8 (range 1–21) and 13 (1–46) months, median OS 15 (1–69) and 26 (4–93) months, respectively. The 13 platinum-resistant patients with a platinum-therapy free interval <6months had a significant shorter PFS (4 versus 10months, p=0.035) and OS (9 versus 15months, p=0.002).

Conclusion

Six cycles weekly paclitaxel/carboplatin followed by six 3-weekly cycles is well-tolerated and highly active in platinum-resistant and platinum-sensitive patients.

Correspondence: Research on Chemotherapy-Induced Nausea: Back to the Past for an Unmet Need?

pdf

New Genetic Findings Should Revolutionize Cancer Screening

Medscape

"....Genetic variants that increase the risk for ovarian cancer were also found, but the magnitude of the increase was much lower — only 4% — compared with 30% for breast cancer and 50% for prostate cancer. "We have much further to go," said coauthor Paul Pharoah, MD, PhD, from the Department of Oncology at Cambridge University in the United Kingdom. "This is probably not sufficient to have clinical relevance," he said.......