: ԤŪ- Astrology

ԤŪ- Astrology

Ѥ줳ԤŪ-Astrology
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ˡܥ٥Хޥ vs. ˡܥĥޥ֤ΥಽII

Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer
The UNICANCER PRODIGE18 Randomized Clinical Trial


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Abstract
Importance Second-line treatment with chemotherapy plus bevacizumab or cetuximab is a valid option for metastatic colorectal cancer.

Objective To evaluate the progression-free survival (PFS) rate at 4 months with chemotherapy plus bevacizumab vs cetuximab for patients with progression of metastatic colorectal cancer after bevacizumab plus chemotherapy.

Design, Setting, and Participants A prospective, open-label, multicenter, randomized phase 2 trial was conducted from December 14, 2010, to May 5, 2015. The main eligibility criterion was disease progression after bevacizumab plus fluorouracil with irinotecan or oxaliplatin in patients with wild-type KRAS exon 2 metastatic colorectal cancer. All analyses were performed on the modified intent-to-treat population.

Interventions Patients were randomized to arm A (FOLFIRI [fluorouracil and folinic acid combined with irinotecan] or modified FOLFOX6 [fluorouracil and folinic acid combined with oxaliplatin] plus bevacizumab) or arm B (FOLFIRI or modified FOLFOX6 plus cetuximab); the second-line chemotherapy regimen was chosen according to first-line treatment (crossover).

Main Outcomes and Measures The primary end point was the 4-month PFS rate. Secondary end points included safety, objective response rate, overall survival, and PFS.

Results A total of 132 patients (47 women and 85 men; median age, 63.0 years [range, 33.0-84.0 years]; 74 patients with an Eastern Cooperative Oncology Group performance status of 0, 54 patients with a performance status of 1, and 4 patients with unknown performance status) were included at 25 sites. The 4-month PFS rate was 80.3% (95% CI, 68.0%-88.3%) in arm A and 66.7% (95% CI, 53.6%-76.8%) in arm B. The median PFS was 7.1 months (95% CI, 5.7-8.2 months) in arm A and 5.6 months (95% CI, 4.2-6.5 months) in arm B (hazard ratio, 0.71; 95% CI, 0.50-1.02; P = .06), and the median overall survival was 15.8 months (95% CI, 9.5-22.3 months) in arm A and 10.4 months (95% CI, 7.0-16.2 months) in arm B (hazard ratio, 0.69; 95% CI, 0.46-1.04; P = .08). A central analysis of KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), and BRAF (V600) was performed for 95 tumor samples. Eighty-one patients had wild-type KRAS and wild-type NRAS tumors.

Conclusions and Relevance The results of the PRODIGE18 (Partenariat de Recherche en Oncologie DIGEstive) study showed a nonsignificant difference but favored continuation of bevacizumab with chemotherapy crossover for patients with wild-type RAS metastatic colorectal cancer that progressed with first-line bevacizumab plus chemotherapy.

Trial Registration ClinicalTrials.gov identifier: NCT01442649 and clinicaltrialsregister.eu identifier: EUDRACT 2009-012942-22

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ǥХwiki
https://ja.wikipedia.org/wiki/%E3%83%87%E3%82%A3%E3%82%AA%E3%83%90%E3%83%B3%E4%BA%8B%E4%BB%B6

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ǶΥ˥塼顡ǥХ vol.1
http://blog.livedoor.jp/aruaru1/archives/52080005.html
ǶΥ˥塼顡ǥХ vol.2
http://blog.livedoor.jp/aruaru1/archives/52083031.html
ǶΥ˥塼顡ǥХ vol.3
http://blog.livedoor.jp/aruaru1/archives/52083908.html
ǶΥ˥塼 ǥХ vol.4
http://blog.livedoor.jp/aruaru1/archives/52084382.html
ǶΥ˥塼 ǥХ vol.5
http://blog.livedoor.jp/aruaru1/archives/52091032.html



٤ʬҥץեδä˸ǷΤΥåˡ:
MyPathway ץ٥ II, ʣΥХåȸ


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http://ascopubs.org/doi/abs/10.1200/JCO.2017.75.3780


RAPID COMMUNICATIONS Clinical Trials

Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study

Purpose
Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer.
These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear.
The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments.

Methods
MyPathway (ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study.
Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively.
The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort.

Results
Between April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment.
The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation.
Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2–amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non–small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%).

Conclusion
The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.


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http://www.nikkei.com/news/print-article/?R_FLG=0&bf=0&ng=DGXMZO16307280S7A510C1X11000&uah=DF220320167113




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A new urgency to protect survivors of childhood cancer

https://www.washingtonpost.com/national/health-science/a-new-urgency-to-protect-survivors-of-childhood-cancer/2016/12/25/f29abb92-c0a8-11e6-afd9-f038f753dc29_story.html?utm_term=.2e992b117e67

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A new urgency to protect survivors of childhood cancer
By Laurie McGinley December 25, 2016

Brittany Galan, 24, was diagnosed with leukemia when she was 6 weeks old. (Tamir Kalifa/For The Washington Post)
SAN ANTONIO — When Brittany Galan was diagnosed with leukemia at 6 weeks old, doctors warned her parents she had little chance of surviving — she was so young and so sick. But after being treated with chemotherapy, I lived and lived! said the exuberant 24-year-old. Everyone calls me the miracle baby.

The lifesaving chemo, however, took a heavy toll. It messed me up neurologically, Galan said. In grade school, she had trouble with reading and math and eventually went on ADHD medication. In college, the once-avid runner developed a heart problem. Recently, Galan, who juggles two part-time jobs working with children with emotional problems, began taking medication for anxiety and depression.

Sometimes I think, Whats next?  she said. I take a lot of pills. I feel like an old lady.

One of medicines greatest successes is the sharp rise in survival rates for children with cancer. But the flip side of that success is that many of those children are turning up years or even decades later with serious and sometimes life-threatening complications, including second cancers, heart disorders, cognitive problems and infertility.

These treatments seem to accelerate the aging process, said Greg Aune, a researcher and pediatric oncologist who works at a clinic for childhood cancer survivors at University Hospital in San Antonio, where Galan gets her care.

Aune, like a growing number of scientists and clinicians, is focusing intently on late effects of cancer treatments. Many of these researchers work in clinics designed specifically to monitor the health of childhood cancer survivors and alert them to potential risks. With the ranks of survivors swelling, there is an urgent need to understand the treatments effects on the entire body, not just the tumor, and to come up with less-toxic therapies.

Greg Aune speaks at The Washington Post Lives Chasing Cancer Summit in December. (Marvin Joseph/The Washington Post)
Aune has a personal stake in the research. As a teenager growing up on a wheat farm in eastern Washington state, he was diagnosed with Hodgkins lymphoma and treated with intensive radiation and chemo. Two decades later, he ended up in emergency surgery to replace a badly scarred heart valve and three blocked arteries, a direct result of the treatment. At 41, he had a mild stroke while at his daughters gymnastics class and was diagnosed with diabetes. His childhood cancer treatment saved his life, and at 43, he appears robust, but he worries that his battered heart might fail.

If I had been born a lot earlier, I wouldnt have to worry about late effects because I wouldnt be here, Aune said.

In the 1960s, fewer than half of children with cancer were alive five years after their diagnoses; now, more than 80 percent are. There are more than 420,000 childhood cancer survivors in the United States today, and the number is expected to increase to 500,000 by 2020.

[8-year-old girl with hard-to-treat leukemia gets groundbreaking treatment ]

Yet the improved survival rates came at a high cost, said Gregory Armstrong, an oncologist at St. Judes Childrens Research Hospital in Memphis. He runs the National Cancer Institute-sponsored Childhood Cancer Survival Study, which tracks more than 30,000 childhood cancer survivors. In the 1980s, survivors began worrying about new health problems, but the severity and connection to their treatments were not appreciated until years later. This is a population that appears much older than its chronological age, Armstrong said.


Ava's hope: immunotherapy new weapon in leukemia fight Play Video3:31
8-year-old Ava Christiansen has been battling cancer for half her life. Now a new specialized cancer treatment may be able to keep her in remission. (Whitney Leaming/The Washington Post)
As cancer doctors realized that patients might live not just for another five years but for another five decades or more, their just-keep-them-alive impulse evolved. Doctors carefully cut back on chemo and radiation for patients who seemed unlikely to relapse.

The less-punishing therapies bolstered long-term survival. Almost 11 percent of five-year survivors diagnosed with cancer in the 1970s were dead within 15 years of their diagnoses; that dropped to less than 6 percent for those treated in the 1990s, according to Armstrongs research.

Still, patients continue to suffer from severe late effects. By age 50, 1 in 3 women who received chest radiation for Hodgkins lymphoma will develop breast cancer, compared with less than 1 in 20 in the general population, Armstrong said.

People who develop cancer as adults also can suffer from late effects. But children are more vulnerable to toxic therapies because their bodies are still developing, researchers say. And they have many more years of life in which complications can occur.

Immunotherapy, a new approach that uses the bodys immune system to fight cancer, could cause less collateral damage — but its use in children is a long way off. For every patient I saw last week, I used the same medications we have had for the last 30 years, Aune said. And they are very toxic.


Brittany Galan underwent chemotherapy for two years, starting when she was an infant. She has since had learning disabilities and heart problems. (Tamir Kalifa/For The Washington Post)

A drug to heal the heart

When Aune is not caring for patients at University Hospital, he spends much of his time in nearby Greehey Childrens Cancer Research Institute, where he oversees experiments in mice on the effects of chemo, including drugs called anthracyclines that can be toxic to the heart. Much of the research on late effects involves the heart, which is especially vulnerable to aggressive childhood treatments.

On a recent day, his lab manager, Thomas Andrews, anesthetized an 8-week-old mouse before laying it on its back on a heated board. With a cotton swab smeared with Nair, he removed a bit of fur from the animals chest, then used a very small probe to take a scan, shown on a monitor, of the mouses left ventricle. The echocardiogram allowed Andrews to measure the animals heart-pumping efficiency.

[FDA: Repeated anesthesia may harm the brains of babies and toddlers]

The mouse was destined for a study looking at whether vigorous exercise can limit heart problems caused by doxorubicin, which is also known as Adriamycin and is an anthracycline. After the mice receive several doses of the drug, some are put on treadmills for exercise, and others are not. Early data suggest that the ones on the treadmills do better, Aune said.

Another mouse experiment involves a medication called dexrazoxane, which is used to prevent heart damage caused by certain chemo drugs in breast-cancer patients. Its use in children has been controversial and spotty because some older studies have suggested that the medication, which is given at the same time as chemo, increases the risk of second cancers. There have also been concerns that it could blunt the cancer-fighting effectiveness of chemo.


But those worries have been largely disproved in recent years, and now a clinical trial in humans may be paving the way for widespread use of the drug, also called Zinecard.

Eric Chow, an oncologist at Fred Hutchinson Cancer Research Center in Seattle, is leading an effort to see whether the drug prevents long-term cardiac deterioration. He and other researchers are scrutinizing the cardiac function of people who were in trials in the late 1990s and early 2000s and treated with either doxorubicin alone or the chemo drug plus Zinecard, the heart-protectant.

We didnt really know what happened to those patients and what happened in terms of heart disease, Chow said. Did the medication have any protective effects that could be detected 20 years later?

A preliminary analysis released earlier this month showed that the Zinecard group appeared to have more preserved heart function many years later. One theory is that the drug interferes with a protein that makes heart tissue more vulnerable to certain chemo agents.

Saro Armenian, a pediatric oncologist at City of Hope in Duarte, Calif., is taking another approach to counter the heart-damaging effects of anthracycline drugs. He is exploring whether giving childhood cancer survivors a common blood pressure drug will prevent heart failure as they get older.

The question is, he said, if you have been treated with chemo, can you take a drug to help the heart to heal? He likened the approach to using low-dose baby aspirin to protect arteries among the general population.


Terri Rupar, national digital editor for The Washington Post; Aune; Ariella Chivil, patient advocate; and Matthew Zachary, founder of Stupid Cancer, participate in a panel discussion during The Washington Post Lives Chasing Cancer Summit. (Kristoffer Tripplaar/For The Washington Post)

Galan embraces Zeff Gomes, a medical technologist who was part of the team that helped treat her childhood cancer, after running into him at a restaurant in San Antonio. (Tamir Kalifa/For The Washington Post)

Survivors clinic

Six-year-old Sammy Cuevas, decked out in black pants and a matching vest, watches videos on his mothers phone as he waits for his checkup at the University Hospital survivors clinic. When he was 4 months old, he had surgery to remove a brain tumor called a medulloblastoma, followed by a year of chemo. There were times, said his mother, Claudia Cuevas, when I thought, The cancer wont kill him, but the chemo will. 

He already has chemo-related problems, including mild deafness, severe constipation and what his doctors call an overall failure to thrive. At 34 pounds and a little over 3 feet tall, the first-grader is in the third percentile for size for his age. As Sammy gets older, he will be monitored for late effects including leukemia and fertility problems.


Nevertheless, Sammys doctor, Shafqat Shah, is optimistic about Sammy. Our hopes for him are pretty dang good, she said. His mother also was upbeat. Hes very good with numbers, she told the doctor. But he has a little trouble with pronunciations because of his hearing problem.

Patients are referred to the survivors clinic — officially called the South Texas Pediatric Cancer Survivorship Program — three to five years after they are finished with treatment, when the threat of relapse has receded. Depending on their anticancer regimen, they may get comprehensive blood tests, echocardiograms, lung function tests and hearing examinations. Red flags prompt immediate referrals to specialists.

On a recent day in a clinic conference room, a few teenagers talked about life as childhood cancer survivors. High school senior Katelyn Garcia, who developed leukemia at 14 months and struggled with learning disabilities and seizures in middle school, is now headed to college and wants to become a child-life specialist — someone who takes care of children undergoing cancer treatment. Her friend, Carmen Villarosa, who had a kidney tumor when she was younger, worries that her cancer treatment might make it difficult for her to have children when she is older.


Galan plays with her niece, Eva Marie Galan, 2, in the back yard of her parents' home in San Antonio. (Tamir Kalifa/For The Washington Post)
[How research involving dogs might help cure cancer in humans]

Bryon Martinez, who was diagnosed with leukemia in the fifth grade and gets annual echocardiograms to check for heart problems, is an accomplished cross-country runner who hopes to go to Georgetown University and become a pediatric oncologist. When his mother, Ana Isabel Martinez, speaks in Spanish about his illness, she weeps quietly. It was extremely difficult, she said.

Aune knows what the survivors are going through. When he was diagnosed with Hodgkins lymphoma, he said, people told me it was a good cancer, because it was fairly curable. Everyone said I should just get through the treatment, and then life would go back to normal.

At the time, his mother wisely urged him to bank his semen, an experience the 16-year-old found almost unbearably embarrassing. My doctors didnt mention it, he said, My mother read about it in Readers Digest.


After he had surgery for the cancer, Aune had radiation to his chest and abdomen for nine weeks and received eight chemo drugs over nine months. He lost 70 pounds. It was years before he felt normal again.

Later, as a 35-year-old training to become a pediatric oncologist at the University of Texas Health Science Center, he became so exhausted that he could not walk more than 30 steps — a fatigue he attributed to a demanding job and four small children but was actually due to the radiation and, probably, the chemo. (By then, he and his wife had managed to have two sets of twins via artificial insemination.)

After having heart surgery, he switched his career focus to late effects, vowing to fill research gaps and work with survivors. Having already dealt with a raft of medical problems, he is philosophical about his future. You never know whats going to come your way, he said, so you better do what you want to do now.

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