by Kristin Jenkins 
Contributing Writer, MedPage Today

The first randomized phase III clinical trial to compare irinotecan (Camptosar, Camptothecin-11, CPT-11) and cisplatin (Platinol, Platinol-AQ, CDDP) with standard of care -- paclitaxel (Taxol, Onxal) plus carboplatin (Paraplatin) -- in patients with clear cell carcinoma (CCC) of the ovary found no significant survival benefit between the groups.

With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the irinotecan-plus-cisplatin (CPT-P) group and 77.6% in the paclitaxel-plus-carboplatin (TC) group (HR 1.17; 95% CI 0.87 to 1.58). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (HR 1.13; 95% CI 0.80 to 1.61).

Both regimens were well tolerated, although the toxicity profiles differed significantly, Aikou Okamoto, MD, of Jikei University School of Medicine in Tokyo and colleagues in the Japanese Gynecologic Oncology Group reported online in theJournal of Clinical Oncology.

"The previous randomized phase II study[JGOG3014] showed a tendency of progression-free survival superiority of the CPT-P arm in a subset analysis of patients without residual disease or with residual disease of less than 2 cm," the researchers wrote. "However, we could not identify the survival advantage of CPT-P in any subgroup analyses by region, stage, and size of the residual disease in the current phase III randomized trial."

The study also revealed the limitations of existing anticancer agents to improve prognosis in patients with ovarian CCC. Identification of driver mutations "is a crucial first step toward personalizing treatment of CCC," Okamoto and colleagues emphasized.

Studies of metastatic clear cell renal cancer have demonstrated the effectiveness of using a combination of targeted treatments such as a PI3K-Akt-mTOR pathway inhibitor as well as anti-angiogenic agents and new immunotherapy drugs, the researchers said. "Therefore, we emphasize that therapeutic regimens should consider such combinations and/or target drugs to improve the prognosis of CCC of the ovary."

The negative results of this trial highlight two major challenges in cancer research,Emese Zsiros, MD, PhD, of Roswell Park Cancer Institute in Buffalo, NY, said in an interview.

"In vitro studies on cancer cell lines often do not translate to clinical benefit in patients given the heterogeneity and complexity of cancer in real life," she explained. "Also, if a phase II study does not show significant activity of a new drug or drug combination, it is unlikely to detect a significant clinical benefit in a large phase III study."

Zsiros, who was not affiliated with the study, also noted that while CCC accounts for only 4-12% of all ovarian cancers in the U.S. and Europe, it is much more common in Japan, accounting for more than 20% of all ovarian cancers.

Unlike serous ovarian cancer, CCC is often associated with a large one-sided pelvic mass and an increased incidence of hypercalcemia and vascular thromboembolic complications such as deep venous thrombosis and/or pulmonary embolism, she pointed out. The lower proliferation rate and increased resistance to traditional chemotherapeutic agents make CCC "a much more difficult disease to treat."

Given the relatively poor prognosis and similarity to clear cell renal cancer, patients with CCC of the ovary are best treated as part of a clinical trial exploring alternative or novel agents, Zsiros suggested.

In the international, multi-institutional study, 667 patients were recruited at 129 centers in Japan, Korea, France, and the U.K., from September 2006 to February 2011. Japanese women made up 93.5% of the study population.

The median age in both the experimental and standard-of-care groups was 53. A total of 411 patients (66.4%) had stage I disease, and 33.6% had stage II to IV disease. Of the latter group, 23% had stage III/IV disease.

Patients were randomly assigned to receive either:

• irinotecan at 60 mg/m² on days 1, 8, and 15 plus cisplatin at 60 mg/m²on day 1 every 4 weeks for six cycles (CPT-P group); or
• paclitaxel at 175 mg/m² plus carboplatin at an area under the curve of 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group).

Of the 619 patients eligible for evaluation, the 332 in the CPT-P group experienced more grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia. The 335 patients in the TC group had grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain more frequently, the study showed.

No deaths related to treatment were reported, the researchers said.

Okamoto disclosed no conflicts of interest, but several of the other study authors disclosed relationships with industry.

• Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

• This activity is part of our Clinical Context curriculum in Gynecologic Cancers

LAST UPDATED 07.15.2016

• Primary Source

Journal of Clinical Oncology

Source Reference: Okamoto A, et al "Randomized phase III trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first-line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG trial"JCO 2016; DOI: 10.1200/JCO.2016.66.9010.

A new study led by Assistant Medical Professor Philip Smith of The City College of New York's Sophie Davis Biomedical Education/CUNY School of Medicine, and conducted in collaboration with researchers at Yale University and Yeshiva University, found important differences between women and men in their ability to quit smoking when taking medications commonly prescribed to help smokers quit.

The study, "Sex Differences in Smoking Cessation Pharmacotherapy Comparative Efficacy: A Network Meta-analysis," which reviewed and analyzed evidence from over 14,000 cigarette smokers participating in 28 clinical trials for nicotine patch, varenicline and bupropion, found that across the trials women who were given varenicline were much more likely to quit smoking than women who were given nicotine patch or bupropion. By contrast, among men there were no differences in the likelihood of successfully quitting smoking when given varenicline, bupropion or nicotine patch.

While the study found that all three medications helped both women and men quit when compared to placebo, the difference was in the relative benefit of the three medications. Clinical trial data consistently show that taking medications can help smokers quit. Some may help more than others, and for women the best choice may be varenicline.

"Before our study, research had shown that among the choices for medications for smokers who wanted to quit, varenicline was the clear winner when it came to promoting quitting," said Smith. "Our study shows this is clearly the case for women. The story seems less clear among men, who showed less of a difference when taking any of the three medications."

Roughly one in six adults in the United States smokes cigarettes, which contributes to over 550,000 deaths per year in the U.S. Currently, three types of medications approved by the U.S. Food and Drug Administration can be prescribed to help smokers quit: nicotine replacement therapies, which include the nicotine patch and nicotine gum; varenicline, which is manufactured by Pfizer and sold as Chantix in the United States; and bupropion, which is manufactured by GlaxoSmithKline and sold as Wellbutrin or Zyban.

The study appears in the journal Nicotine & Tobacco Research.

Story Source: The above post is reprinted from materials provided by City College of New York. Note: Materials may be edited for content and length.

Journal Reference:

Sherry A. McKee, Philip H. Smith, Mira Kaufman, Carolyn M. Mazure, Andrea H. Weinberger. Sex Differences in Varenicline Efficacy for Smoking Cessation: A Meta-Analysis. Nicotine & Tobacco Research, 2016; 18 (5): 1002 DOI: 10.1093/ntr/ntv207

City College of New York. "Study finds differing treatment options for women smokers." ScienceDaily. ScienceDaily, 13 July 2016. <www.sciencedaily.com/releases/2016/07/160713105742.htm>.

AAPA

In a landmark partnership, the Centers for Disease Control and Prevention and AAPA will present a free webinar on Zika and pregnancy on July 28 from 2-3 p.m. EDT. The presentation qualifies as Category 1 CME.

The World Health Organization declared Zika virus a public health emergency of international concern after local transmission was reported in many other countries and territories. With the likelihood that the Zika virus will continue to spread to new international and domestic areas, this webinar is an opportunity for PAs to be prepared to handle Zika by knowing the facts. Pre-register (at no cost) and view the detailed agenda here. 

AAPA is looking for 10-15 PAs in various specialties who are willing to be interviewed and provide their thoughts and attitudes on the development of clinical apps that would be used via smartphones. The goal of the project is to learn what features and characteristics make medical apps effective and user-friendly for healthcare professionals and to gather information on using an "App Store" approach to enhancing electronic health records (EHR) functionality.

Interviews will be conducted via phone by KLAS marketing research firm and will take no more than 15 minutes. During the interview you will also have an opportunity to provide ideas and suggest questions that will be part of a larger survey that will go out to PAs, physicians, advanced practice nurses in the future.

The project is funded by a grant from the Office of the National Coordinator for Health Information Technology (ONC). ONC is the principal federal entity charged with coordination of nationwide efforts to implement and support the adoption of advanced health information technology within the healthcare arena.

We would appreciate hearing from interested PAs by Friday, July 22.

For additional information or to volunteer contact Michael Powe, AAPA's Vice President of Reimbursement & Professional Advocacy at michael@aapa.org.

July 13, 2016

Over the past year, AAPA aggressively lobbied for PAs to be part of the solution to the nation’s opioid epidemic. As a result of our efforts, PAs will soon be eligible to become waivered to prescribe buprenorphine for the treatment of opioid addiction. On July 8, the U.S. House of Representatives overwhelmingly supported passage of the House-Senate Conference report to S. 524, the Comprehensive Addiction and Recovery Act (CARA) of 2016 and the U.S. Senate followed suit on July 13. The legislation amends federal law (the Drug Addiction Treatment Act of 2000 orDATA 2000) to permit PAs to become waivered to prescribe buprenorphine for the treatment of opioid addiction.  It will now be sent to the president for his expected signature.

“As a PA with a background in addiction medicine and community health clinics, I am pleased Congress is bringing more resources to bear to tackle the opioid addiction crisis in this country," said AAPA President Josanne Pagel. “The inclusion of PAs in CARA is crucial to our ability to provide proven treatment options to more Americans suffering from addiction.”

Although CARA was crafted in a bipartisan manner, funding was a contentious issue leading up to the bill’s passage and shaped many of the bill’s final provisions. This was because the Congressional Budget Office gave the bill a high cost estimate for the Medication-Assisted Treatment (MAT) Program, Section 303, of the bill. This unexpectedly high cost ultimately determined the conditions in which DATA 2000 was amended to permit PAs and nurse practitioners (NPs) to become waivered to prescribe buprenorphine for the treatment of opioid addiction. The final version of the Section 303 MAT Program:

• Authorizes PAs and NPs to become waivered to prescribe buprenorphine in MAT for a five-year period, expiring in 2021;
• Allows newly-waivered PAs, NPs, and physicians to prescribe buprenorphine to 30 patients, with the option to treat up to 100 patients after one year if certain conditions are met;
• Requires PAs and NPs to obtain 24 hours in education related to the treatment of opioid addiction as a condition to be waivered; the law includes AAPA in the list of professional associations who may provide the educational requirements; additionally, the law provides the secretary of the Department of Health and Human Services (HHS) the flexibility to adjust the 24-hour educational requirement for clinicians with demonstrated experience in treating patients struggling with addiction;
• Defers to state law regarding whether a PA or NP works with a physician through a supervisory or collaborative relationship; however, the legislation requires that a physician who supervises or collaborates with a PA or NP must also be waivered to prescribe buprenorphine to treat addiction; given the small number of waivered-physicians, particularly in rural and other medically underserved communities, AAPA is concerned this requirement will limit the number of PAs and NPs who will become waivered; fortunately, there is also a provision in the bill that provides flexibility to the HHS Secretary to review and remove the requirement.

According to Tillie Fowler, AAPA’s senior vice president for advocacy and government relations, “Although Section 303 of CARA does not include all of AAPA’s policy recommendations; we believe it is a significant step forward in utilizing PAs to expand access to treatment for the millions of Americans who are struggling with opioid addiction. And AAPA will push to extend this authorization for PAs beyond its current 2021 expiration date.”

In addition to MAT, CARA contains numerous programs and provisions designed to:

• Support and provide grants for education, prevention, treatment, and recovery efforts to confront the opioid epidemic and assist individuals and communities suffering from addiction to opioids and heroin;
• Provide grants to expand access to naloxone and prescription drug monitoring programs and to support veterans and law enforcement.

Enactment of CARA is a significant win in AAPA’s continued efforts to ensure PAs have the ability to be part of the solution to the nation’s opioid epidemic. The Academy presented multiple statements and letters to Congress on the need to permit PAs to prescribe buprenorphine for the treatment of opioid addiction; extensively lobbied committee staff and members, as well as House and Senate leadership; and held joint lobbying visits with the American Association of Nurse Practitioners. AAPA will continue its work through the development of regulations to implement the MAT Program.

- See more at: https://www.aapa.org/twocolumn.aspx?id=6442451389#sthash.Ev0XpXcU.hDmrNspU.dpuf

Medscape 

Overall, adverse event rates are comparable between the two vaccines, although injection-site AEs are more common with the 9-valent human papillomavirus vaccine (9vHPV) (Gardasil 9, Merck & Co., Inc.) than with the quadrivalent HPV (qHPV) vaccine (Gardasil, Merck & Co., Inc.), and they increase with subsequent doses for both vaccines, a new analysis concludes. 

Read more

Media Statement

Embargoed until: Friday, July 15, 2016, 11 AM, EDT
Contact: Media Relations,
(404) 639-3286

The New York City report of female-to-male sexual transmission of Zika virus infection is the first documented case of sexual transmission of Zika from a woman to her sex partner and adds to the growing body of knowledge about the sexual transmission of Zika. All previously reported cases of sexually transmitted Zika virus infection have been spread from men to their sex partners.

CDC recommends that all pregnant women who have a sex partner who has traveled to or resides in an area with Zika use barrier methods every time they have sex or they should not have sex during the pregnancy. Although no cases of woman-to-woman Zika transmission have been reported, these recommendations now also apply to female sex partners of pregnant women.

CDC is currently updating recommendations for sexually active people in which the couple is not pregnant or concerned about pregnancy and for people who want to reduce personal risk of Zika infection through sex.

###
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

High energy sound waves could treat a potentially deadly complication that affects some twin pregnancies, says new research.

The early-stage feasibility study involving sheep suggests High Intensity Focused Ultrasound - a technique already used for treating some cancers - could help a condition called Twin-Twin Transfusion Syndrome (TTTS). It was conducted by researchers from Imperial College London and the University of Cambridge, with technology being developed at The Institute of Cancer Research, London.

Twin-Twin Transfusion Syndrome occurs in around one in seven identical twin pregnancies, and leads to one baby growing much larger than the other due to abnormal blood vessels in the placenta.

Some identical twins share a placenta, which provides the babies with equal amounts of oxygen and nutrients, carried in the blood. However in TTTS the shared placenta contains abnormal blood vessels that cause more blood to flow to one baby, leaving the other deprived of oxygen and nutrients.

This affects the twins' growth, and can result in complications such as premature birth, handicap or even death of one or both babies.

Severe cases can be treated by using a laser to destroy the abnormal blood vessels, so that each baby has a separate supply of oxygen and nutrients.

However, this involves making a small hole in the womb and carries a risk of infection or miscarriage, explained Dr Christoph Lees, senior author from the Department of Surgery and Cancer at Imperial: "Twin-Twin Transfusion Syndrome can have tragic consequences, and in severe cases results in one tiny twin, while the other is very large - and begins to squash its sibling in the womb. Unfortunately, the little baby often does very badly - and in some cases the condition results in the loss of both twins.

Color Doppler and B-mode ultrasound imaging of placental vascular ablation. (A) Pretreatment color Doppler imaging of a placentome. (B) Posttreatment color Doppler imaging of the same placentome demonstrating no flow within the targeted vessel. (C) B-mode harmonic ultrasound imaging of hyperechoic region within the high-intensity focused ultrasound (HIFU) focal zone. Credit: Shaw et al. / Science Translational Medicine (2016)

"Yet at the moment the only option we have for these serious cases - laser treatment - carries risk of premature birth or miscarriage. Furthermore, the laser can sometimes not reach some abnormal vessels deep in the placenta."

In the new study, published in the journal Science Translational Medicine, the team showed that High Energy Focused Ultrasound (HIFU) can selectively target and destroy placental blood vessels - potentially enabling it to split the placenta in two without the need for an invasive procedure. The technique creates a beam of high energy sound waves that generate heat, and kill cells. It is already used to treat prostate cancer and fibroids.

To establish whether the procedure could destroy placental blood vessels, the team used the technique on 11 anesthetised pregnant sheep - five had the HIFU procedure while six had a placebo procedure.

Although the sheep did not carry twins, the blood vessels in the sheep placenta have a similar structure to blood vessels in the human placenta, enabling the researchers to assess whether the HIFU could separate the placenta in TTTS. Furthermore, the fetuses of sheep and humans are a similar size.

The results showed the technique was successful, and could destroy blood vessels without damage to the fetus. The researchers used the HIFU probe against the wall of the uterus, through an incision in the abdomen - and carried out further experiments to show the procedure works through the skin.

Dr Lees added: "Although this is very early-stage research, it shows the procedure can successfully destroy blood vessels in the placenta - and could potentially stop abnormal blood flow between twin babies. We now hope to continue developing this HIFU procedure, translate these findings to humans, and work towards human trials."

The team added that because the non-invasive technique could potentially be performed at an earlier stage in the pregnancy, this could further reduce chance of complications. The laser procedure is usually performed at around five months into the pregnancy, once the womb is big enough to accommodate the laser being inserted. However, the current study suggests the procedure may work even earlier, at around three-four months into the pregnancy.

More information: "Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study," Science Translational Medicine,stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaf2135 

Provided by Imperial College London

"Sound waves may hold potential to treat twin pregnancy complications" July 13, 2016 http://medicalxpress.com/news/2016-07-potential-twin-pregnancy-complications.html

The 20^th Biennial International Perinatal Bereavement Conference is coming up this fall — September 28 – October 1st in Phoenix, Arizona — and its sponsor wants to help you get there. The Pregnancy Loss and Infant Death Alliance (PLIDA) will be awarding 24 scholarships to professional care providers, parent advocates, and researchers to attend the event.

The conference focuses on care for families who have experienced a perinatal death, as well as research on related topics. This scholarship would be ideal for PAs who work or research in the fields of family practice, obstetrics, maternal fetal medicine, or neonatology.

The scholarship will cover the cost of the conference, but applicants should note that all other expenses (e.g., food, travel, lodging) are not included. Any member of PLIDA who can show financial need is invited to apply.

The deadline to apply is August 5. For more information, visit the conference website.

AAPA

In a landmark partnership, the Centers for Disease Control and Prevention (CDC) and AAPA will present a free webinar on Zika and pregnancy on July 28 from 2-3 p.m. EDT. The presentation qualifies as Category 1 CME.

The World Health Organization declared Zika virus a public health emergency of international concern after local transmission was reported in many other countries and territories. With the likelihood that the Zika virus will continue to spread to new international and domestic areas, this webinar is an opportunity for PAs to be prepared to handle Zika by knowing the facts.

At the end of the webinar, you will be able to:

• List the ways pregnant women become infected with the Zika virus;
• Describe CDC recommendations for testing of pregnant women with possible exposure;
• Describe CDC recommendations for testing of couples interested in conceiving who reside in an active Zika virus transmission area;
• Describe the implications of Zika virus infection;
• And identify the cases that meet criteria for inclusion in the U.S. Zika Pregnancy Registry.

Don't miss this special opportunity, eligible for free CME for PAs.

Zika Virus — Implications for Pregnant Women
Date: Thursday, July 28
Time: 2–3 p.m. EDT
Sign up: Pre-register (at no cost) and view the detailed agenda.