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Paraneoplastic thrombocytosis in ovarian cancer. Paraneoplastic thrombocytosis in ovarian cancer. February 18, 2012

Posted by patoconnor in cancer, gynecological cancer, ovarian cancer, tubal cancer, Uncategorized, uterine cancer, vaginal cancer.
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Paraneoplastic thrombocytosis in ovarian cancer.

Feb 2012

Stone RLNick AMMcNeish IABalkwill FHan HDBottsford-Miller JRupaimoole RArmaiz-Pena GNPecot CV,Coward JDeavers MTVasquez HGUrbauer DLanden CNHu WGershenson HMatsuo KShahzad MMKing ER,Tekedereli IOzpolat BAhn EHBond VKWang RDrew AFGushiken FCollins KDeGeest KLutgendorf SKChiu W,Lopez-Berestein GAfshar-Kharghan VSood AK.


Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA.



The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.


We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.


Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.


These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).


Body Weight Makes No Difference in Ovarian Cancer Survival May 25, 2009

Posted by patoconnor in cancer, gynecological cancer, ovarian cancer, tubal cancer, uterine cancer, vaginal cancer.
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Body Weight Makes No Difference in Ovarian Cancer Survival

By Todd Neale, Staff Writer, MedPage Today
Published: December 30, 2008
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

BIRMINGHAM, Ala., Dec. 30 — Obese patients with epithelial ovarian cancer do not appear to have worse survival than their slimmer counterparts, a retrospective chart review showed.

Obese and non-obese patients had similar progression-free survival (17 versus 11 months, P=0.14) and overall survival (48 versus 40 months, P=0.37) following primary cytoreductive surgery that resulted in similar rates of optimal debulking, Kellie Matthews, M.D., of the University Alabama at Birmingham, and colleagues reported online in Gynecologic Oncology.

All patients received chemotherapy administered according to their actual body weight. Often, chemotherapy is administered based on ideal weight, which may lead to insufficient doses for obese patients, according to the researchers.

Some past studies have suggested that obesity is an independent predictor of lower survival in patients with epithelial ovarian cancer, but others have not. Few have included information on differences in rates of optimal debulking between obese and non-obese patients, the researchers said.

To explore the issue, they reviewed charts for 304 patients with FIGO stages II to IV epithelial ovarian cancer from a gynecologic oncology database from 1996 to 2005.

All patients underwent primary cytoreductive surgery followed by IV taxane and platinum-based chemotherapy dosed according to actual body weight.

Nearly a quarter (23.4%) were obese and the rest had a body mass index of less than 30 kg/m2.

Obese and non-obese patients had similar disease stage, grade, and histology, rates of platinum sensitivity, and administration of chemotherapy.

Obese patients were significantly more likely to be younger than 65 (P=0.02) and to be black (P=0.01).

There were no significant differences between the groups in estimated blood loss, time spent in the operating room, or operative complications. Only wound complications were more common in the obese group (11% versus 2%, P<0.001).

Rates of optimal debulking — defined as a lack of residual tumors greater than 1 cm in diameter — were similar in obese and non-obese patients (52% versus 51%, P=0.88), in spite of potential challenges to the surgical treatment of obese patients.

Such potential difficulties include comorbid chronic illnesses, administration of anesthesia, operative complications, and technical challenges, the researchers said.

“This demonstrates that any disadvantage obesity affords in the treatment of ovarian cancer is likely not related to the surgeon’s ability to achieve optimal cytoreduction,” the researchers said.

Although obese patients had a lower recurrence rate (68% versus 79%, P=0.04), there were no significant differences in progression-free and overall survival between the two groups.

The authors acknowledged that the study had several limitations, including the retrospective design, a trend toward poorer outcomes in underweight women that could not be compared with outcomes in obese women because of small patient numbers, potential selection bias, and optimal debulking rates that were lower than those found in other studies.

MedPage Today

Thalidomide For Ovarian Treatment November 23, 2008

Posted by patoconnor in cancer, gynecological cancer, ovarian cancer, tubal cancer, uterine cancer, vaginal cancer.
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Thalidomide For Ovarian Treatment

Nov. 22, 2008

Washington: Thalidomide, a drug banned in the 1950s for causing birth defects, is showing promise as a safe and effective treatment for women with recurrent ovarian cancer, according to a new study.

In the study, led by Levi Downs, Jr., M.D., assistant professor and a researcher of gynecologic oncology at the University of Minnesota Medical School and Cancer Center, Phase II clinical trial was randomized.

“For some women, ovarian cancer has become a chronic disease. The standard chemotherapy regimens can put recurrent cancer in remission, often more than once. However, when the cancer resists the standard treatments, we need new options for treatment,” Downs said.

The study compared the effectiveness and safety of the combination of thalidomide and topotecan, a chemotherapy often used for ovarian cancer, versus topotecan alone for treatment of recurrent epithelial ovarian cancer in patients who had received prior treatment.

Epithelial ovarian cancer is a disease in which cancer cells form in the tissue that covers the ovary.

In the study, 75 women were evaluated who were randomly assigned to receive either the combination of thalidomide and topotecan or only topotecan.

“We found that patients who received topotecan plus thalidomide showed an overall response rate of 47 percent compared to 21 percent response in patients who received only topotecan. In patients receiving topotecan plus thalidomide, 30 percent achieved a complete response, meaning the cancer went away, compared to 18 percent for patients only getting topotecan,” Downs said.

“Furthermore, patients getting topotecan plus thalidomide had a longer cancer-free period after treatment than those receiving topotecan alone. What all of this means is that while thalidomide may not cure ovarian cancer, it may broaden the treatment options available to physicians and provide more hope to women diagnosed with the cancer,” Downs added.

The study has been published in the journal Cancer.