Tuesday, February 14, 2006

Sequential High-Dose Chemotherapy with Stem Cell Support Promising for Recurrent or Refractory Ovarian Cancer

http://patient.cancerconsultants.com/news.aspx?id=36251

Morphotek Announces FDA Acceptance of the IND for MORAb-009, a Monoclonal Antibody for the Treatment of Mesothelin-Expressing Cancers

http://www.docguide.com/news/content.nsf/news/852571020057CCF68525711400734F59

Monday, February 13, 2006

LI OCEANS Links

Surgeon's Area of Specialty Affects Ovarian Cancer Results

http://www.medicinenet.com/script/main/art.asp?articlekey=57654

NCI-Genetics of Breast and Ovarian Cancer

http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page2

WEBCASTS

  1. Can Ovarian Cancer Be Detected Early?

Remember Me as a Writer, Not a Survivor-By Donna Trussell

http://msnbc.msn.com/id/11298625/site/newsweek/

Maze of cystic fibrosis is getting a little clearer- Inflammation & Cancer

http://www.usatoday.com/news/health/2006-02-12-cystic-fibrosis_x.htm

Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16198399&dopt=Abstract

Two NIH Initiatives Launch Intensive Efforts to Determine Genetic and Environmental Roots of Common Diseases

http://www.nih.gov/news/pr/feb2006/nhgri-08.htm

Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16152587&query_hl=19&itool=pubmed_DocSum

Insulin-like Growth Factor Binding Protein-2 Stimulates Proliferation and Activates Multiple Cascades of the Mitogen-Activated Protein Kinase Pathways

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16357519&query_hl=19&itool=pubmed_DocSum

Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16298526&query_hl=19&itool=pubmed_DocSum

Comparison of efficacy and toxicity profile between intraperitoneal and intravenous topotecan in human ovarian cancer xenografts.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16415975&query_hl=19&itool=pubmed_DocSum

Transcriptomic analysis of an in vitro murine model of ovarian carcinoma: Functional similarity to the human disease and identification of prospective

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16245302&query_hl=19&itool=pubmed_DocSum

Cyclin-dependant kinase inhibitors CIP1 (p21) and KIP1 (p27) in ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16328436&query_hl=19&itool=pubmed_DocSum

Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16152612&query_hl=19&itool=pubmed_DocSum

Ligands to FGF receptor 2-IIIb induce proliferation, motility, protection from cell death and cytoskeletal rearrangements in epithelial ovarian cancer

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16393693&query_hl=19&itool=pubmed_DocSum

Palliative care treatment patterns and associated costs of healthcare resource use for specific advanced cancer patients in the UK.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16441679&query_hl=19&itool=pubmed_DocSum

Dietary risk factors for ovarian cancer: the adventist health study (United States).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16425091&query_hl=19&itool=pubmed_DocSum

Studies of interaction of trichloro{eta(2)-cis-N,N-dimethyl-1-[6-(N',N'-dimethyl-ammoniummethyl)-cyclohex-3-ene-1-yl]-methylammonium}platinum(II) chlo

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16256352&query_hl=19&itool=pubmed_DocSum

Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16437378&query_hl=19&itool=pubmed_DocSum

Promoter Hypermethylation of FANCF Plays an Important Role in the Occurrence of Ovarian Cancer through Disrupting Fanconi Anemia-BRCA Pathway.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16418574&query_hl=19&itool=pubmed_DocSum

Comparison of strategies targeting Raf-1 mRNA in ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16184551&query_hl=19&itool=pubmed_DocSum

From gene profiling to diagnostic markers: IL-18 and FGF-2 complement CA125 as serum-based markers in epithelial ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16217764&query_hl=19&itool=pubmed_DocSum

Regional activation of chromosomal arm 7q with and without gene amplification in taxane-selected human ovarian cancer cell lines.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16382445&query_hl=19&itool=pubmed_DocSum

Characterizations of irofulven cytotoxicity in combination with cisplatin and oxaliplatin in human colon, breast, and ovarian cancer cells.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16075278&query_hl=19&itool=pubmed_DocSum

The prognostic role of pre-chemotherapy hemoglobin level in patients with ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16368539&query_hl=19&itool=pubmed_DocSum

Prognostic significance of E-cadherin-catenin complex in epithelial ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16461565&query_hl=1&itool=pubmed_DocSum

Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lin

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16466850&query_hl=1&itool=pubmed_DocSum

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16462769&query_hl=1&itool=pubmed_DocSum

Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15975613&query_hl=1&itool=pubmed_DocSum

MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16139892&query_hl=1&itool=pubmed_DocSum

Transcriptomic analysis of an in vitro murine model of ovarian carcinoma: Functional similarity to the human disease and identification of prospective

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16245302&query_hl=1&itool=pubmed_DocSum

Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16152612&query_hl=1&itool=pubmed_DocSum

Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16161048&query_hl=1&itool=pubmed_DocSum

Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16437378&query_hl=1&itool=pubmed_DocSum

The prognostic role of pre-chemotherapy hemoglobin level in patients with ovarian cancer.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16368539&query_hl=1&itool=pubmed_DocSum

Colon Cancer Condition Linked to Other Cancers

http://www.cancerwise.org/February_2006/display.cfm?id=28864619-222B-4D0D-9C597C437E35C202&method=displayFull&color=red

Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14576434

Ovarian Cancer - New York State Department of Health

http://www.health.state.ny.us/diseases/cancer/ovarian/index.htm

Gain Reported in Combating Ovary Cancer

http://www.nytimes.com/2006/01/05/health/05cancer.html?ei=5070&en=5c4e41494639a8f3&ex=1140066000&pagewanted=all
Gain Reported in Combating Ovary Cancer -NY TIMES
By
DENISE GRADY

A rarely used treatment that pumps cancer drugs directly into the abdominal cavity can add 16 months or more to the lives of many women with advanced cases of ovarian cancer, doctors are reporting.
Medical practice should change immediately to reflect the findings from the study, being published today, as well as those from several earlier studies, cancer experts say.


In the United States there are more than 22,000 new cases each year, and 16,000 deaths. Currently, most women receive
chemotherapy intravenously. They should still do so, but many should get the drugs abdominally as well.

The combined treatment should be offered to every woman who meets the medical criteria for it, the cancer experts say, and doctors who cannot provide it should refer women to clinics that can. They advise that patients ask their doctors about the treatment.

The technique employs two generic drugs already in wide use for ovarian cancer, paclitaxel and cisplatin, and involves high doses that can have severe side effects.

The National Cancer Institute is taking the unusual step of issuing a clinical announcement to encourage doctors to use the abdominal treatment. Such alerts are uncommon. The last one was in 1999, to publicize a major advance in cervical cancer.

"We want to use the bully pulpit of the National Cancer Institute to say that patients and doctors need to be aware of this information," said Dr. Edward Trimble of the cancer institute. He and other cancer experts said that a survival increase of more than a year was extraordinary for any type of cancer, and that new drugs were often approved on the basis of much smaller gains.

The institute is posting information at
http://ctep.cancer.gov/highlights/ovarian.html, along with a list of medical centers that can provide the abdominal treatment. Information can also be obtained from the institute's Cancer Information Service by telephone: (800) 4-CANCER.

"It's really the best news we've had in some time" about ovarian cancer, said Dr. Richard Barakat, chief of gynecologic oncology at Memorial Sloan-Kettering Cancer Center in New York. He predicted that the cancer institute's action would lead to widespread changes in treatment.

"Advanced ovarian cancer is a bad disease," Dr. Barakat said. "Many patients don't do well. When you have a study that shows a 16-month prolongation of median survival, that's a big deal."

Dr. Maurie Markman, vice president for clinical research at the M. D. Anderson Cancer Center in Houston, and a spokesman for the American Society for Clinical Oncology, said that giving abdominal chemotherapy, known as intraperitoneal or IP treatment, was not that demanding technically but would require some training. Medical groups that do not treat many women with ovarian cancer might be better off sending patients to experts in the therapy.

Ovarian cancer is far less common than breast, colon or prostate cancer, but it has a much higher death rate. From 1995 to 2000, 44 percent of patients with ovarian cancer survived five years, as opposed to 87.7 percent with
breast cancer.

The disease is so deadly because it has hardly any symptoms and so is often advanced by the time it is diagnosed. It usually kills by spreading through the abdomen and attacking the intestines, kidneys and other organs. Bloating, weight gain, bowel problems and other vague abdominal symptoms may occur early on, but they are often mistakenly attributed to other ailments, especially in older women. There is no reliable means of early detection.

The new recommendations are based in part on a study being published today in The New England Journal of Medicine. But that study is the third major one in a decade to show benefits from abdominal chemotherapy. The new study had the clearest and most definitive results, researchers said. The cancer institute said five other smaller studies had also supported IP treatment.

The new study, led by Dr. Deborah K. Armstrong of the Johns Hopkins Kimmel Cancer Center, included 415 patients treated at 40 hospitals in the United States. Most were 41 to 70 years old, and all had had surgery to remove the cancer.

About half the women, 210, were chosen at random to get intravenous therapy, and 205 received both intravenous and IP treatment. Patients getting IP treatment had devices and tubing implanted in the abdomen to pipe in the chemotherapy. They received a total of six treatments with both intravenous and IP drugs, given once every three weeks. Basically, the procedure soaks the
tumors in the powerful cancer-killing drugs.

In the intravenous group, the median survival was 49.7 months, but it was 65.6 months in the IP group - a difference of 15.9 months.

Median survival is the time at which half the patients are still alive. Conversely, in this study it means that in the intravenous group, half had died by 49.7 months, but it took 15.9 months longer for half to die in the IP group.

"This is the longest reported survival to date in a randomized trial in ovarian cancer," Dr. Armstrong said. Patients are still alive in both groups: 78 of 210 in the intravenous group, with 5 lost to follow-up, and 93 of 205 in the IP group, with 11 lost to follow-up. The longest survival so far is about 7 years, Dr. Armstrong said.
But the abdominal treatment uses higher drug doses than intravenous therapy and is more likely to cause severe side effects, including fever, infection, nerve problems, fatigue and pain. The implanted tubing can cause problems as well. The side effects are temporary, but even so, because of them, only 42 percent of the patients were able to finish the full course of IP treatment, as opposed to 83 percent in the intravenous group. Women in each group died from complications of treatment, mainly infection: four in the intravenous group and five in the IP group.

Doctors say it is remarkable that the IP group fared so much better even though so few finished the course. The result suggests that even an incomplete course of IP therapy can help women live longer, and that even bigger gains may be possible if the treatment can somehow be made more tolerable.

Dr. Trimble said the cancer institute was taking special pains to publicize the treatment and to encourage patients to push for it because doctors had resisted adopting it despite mounting evidence in its favor. It is more difficult and time-consuming than standard intravenous chemotherapy, Dr. Trimble said. Also, IP was tried for decades in various forms before a successful method was found, and doctors may have given up on it in favor of newer drugs.

"There are no big pharmaceutical companies knocking on people's doors to tell them about" abdominal treatment, Dr. Trimble said.

IP chemotherapy is not a standard treatment for any other kind of cancer, but it is being studied in some other types, including breast and colon cancers that have spread inside the abdomen. The procedure has also been studied for ovarian cancer in Europe, but it is not yet a standard treatment there.

Not every woman with advanced ovarian cancer can have the abdominal treatment. In some, not enough of the cancer can be surgically removed. Or it may not be possible to implant the tubing.

Dr. Armstrong said that extensive and meticulous surgery to remove the cancer was absolutely essential if either the abdominal treatment or standard chemotherapy was to succeed. Such surgery, known as debulking, is more important for this disease than for other types of cancer, because studies have shown it has more of impact on survival. It may require removing parts of the intestine, spleen and other organs.
Ideally, the operation should leave behind no tumors bigger than a centimeter in diameter, or 0.39 inches. The drugs work best when they have fewer cancer cells to kill, and when the tumor masses are small enough for the medicine to penetrate.

This kind of complex operation should be done by a surgeon who is a specialist in gynecologic oncology, said Dr. Armstrong, adding that she is not a surgeon. But she said only about half of women had their operations done by these specialists. General surgeons and gynecologists are not as well trained to perform these cancer operations, or to install the ports needed for IP treatment.

Too often, Dr. Armstrong said, women with ovarian cancer wind up having "peek and shriek" operations in which surgeons who are not gynecologic oncologists open them up, find extensive cancer and close them up again without properly finishing the job.

At some major cancer centers, IP treatment for ovarian cancer is already standard procedure. Memorial Sloan-Kettering Cancer Center is one of them, said Dr. Carol Aghajanian, chief of the gynecologic medical oncology service.

One of her patients, Ann Henriques, 49, of Nyack, N.Y., is most of the way through the therapy now. Ms. Henriques said she had lost much but not all of her hair, and felt some fatigue, soreness and swelling from the treatment, which requires pumping about two quarts of fluid into the abdomen.

"I can't say it's the worst thing in the world, but you do get a little cranky," she said.
But, she added: "It's a lucky thing for me this treatment was available. It's such a bad diagnosis, people look at you like you're going to die, because so many women do. I've just done really well on this treatment. It's an incredible hope."

Gina Kolata contributed reporting for this article.

Recruitment Temporarily Suspended in an International Phase III Trial (AVANT) in Early-Stage Colon Cancer

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/02-13-2006/0004280018&EDATE=

Sequential High-Dose Chemotherapy with Stem Cell Support Promising for Recurrent or Refractory Ovarian Cancer

http://patient.cancerconsultants.com/news.aspx?id=36251

IP Chemotherapy Encouraged for Ovarian Cancer

http://www.cancerwise.org/February_2006/display.cfm?id=C0BB3284-68AD-445A-9255C6D825AFBF8F&method=displayFull&color=green

Still, a Cruel Diagnosis

http://www.washingtonpost.com/wp-dyn/content/article/2006/02/13/AR2006021301531.html