Why women are more likely to die of a heart attack

Heart disease is the No. 1 killer of both men and women in the United States.

Some of the most obvious symptoms of the disease — such as a heart attack — sometimes strike women in different ways.

There are some things you should know when it comes to gender and heart health.

As many people will tell you, men and women are very different creatures.

Video and article at Why women are more likely to die of a heart attack

Yogurt and Diabetes: Overview of Recent Observational Studies

Whew!  At first I thought this might be bad news like so many of these news items seem to be. Coffee is bad for you! Coffee is good for you!…

I’m a huge fan of yogurt and have made my own for many decades, so I was very glad to find nothing bad here.

 

 

Salas–Salvado J, et al. – Analysis of observational studies was performed to determine the association between yogurt consumption and type 2 diabetes, along with possible mechanisms involved. Findings reported that in healthy and older adults at high cardiovascular risk, yogurt consumption, in the context of a healthy dietary pattern, may reduce the risk of type 2 diabetes.

  • Researchers performed a review of observational studies and found that 13 prospective studies assessed the link between yogurt intake and type 2 diabetes, most of which demonstrated an inverse association between the frequency of yogurt consumption and the risk of diabetes.
  • Combined data including scientific evidence accumulated from individual prospective studies and several meta-analyses have shown that yogurt consumption has a potential role in diabetes prevention.
  • According to the most recent analysis, a 14% lower risk of type 2 diabetes was observed when yogurt consumption was 80–125 g/d compared with no yogurt consumption.
  • It was reported that intake of fermented dairy products, especially yogurt, has been inversely associated with variables of glucose metabolism.
  • Data also suggested that yogurt may have probiotic effects that could modulate glucose metabolism.

From https://www.mdlinx.com/family-medicine/medical-news-article/2017/06/21/yogurt-type-2-diabetes-insulin-sensitivity/7213515/?category=latest&page_id=1&utm_source=in-house&utm_medium=message&utm_campaign=tmn-june17-peds

Targeted drug shows promise in rare advanced kidney cancer

Some patients with a form of advanced kidney cancer that carries a poor prognosis benefited from an experimental drug targeted to an abnormal genetic pathway causing cancerous growth, according to research led by a Dana-Farber Cancer Institute scientist.

The drug, savolitinib, showed clinical activity in patients with metastatic papillary renal cell carcinoma (PRCC) whose tumors were driven by overactivity of the MET signaling pathway, but was not effective for patients whose tumors lacked the MET abnormality, said the investigators, led by Toni Choueiri, MD, director, Lank Center for Genitourinary Oncology, and director, Kidney Cancer Center, both of Dana-Farber.

These results from a single-arm, multicenter phase II clinical trial, reported in the Journal of Clinical Oncology, suggest that savolitinib holds promise as a personalized treatment for a subgroup of patients with metastatic papillary renal cell carcinoma, the researchers said.

In the US alone, about 6,400 cases of PRCC are expected to be diagnosed in 2017, compared to a total of 64,000 cases of kidney cancers. The majority of them are classified as clear cell renal cell cancers. Papillary renal cell carcinoma are non-clear cell kidney cancers. No good treatments exist for advanced or metastatic PRCC.

The current trial tested savolitinib, a potent and selective MET inhibitor, in 109 patients with locally advanced or metastatic PRCC. Of the 109 patients, 40 percent had tumors driven by MET, 42 percent had tumors that did not rely on MET, and MET status was unknown in 17 percent of patients.

When the results were analyzed, 18 percent of patients with MET-driven cancers had significant shrinkage of their tumors, and 50 percent had stable disease. By contrast, none of the patients with MET-independent tumors had shrinkage response, and only 24 percent had stable disease.

In addition, the length of time after treatment before the cancer began growing was significantly longer in the MET-driven tumor group – 6.2 months versus 1.4 months.

“These data support the hypothesis that savolitinib has antitumor activity in patients with MET-driven papillary renal cell carcinoma,” the authors wrote. “Our study identified a defined molecular group and highlights the prevalence of MET-driven disease in this rare population of RCC patients.”

Although some patients had their dosage of savolitinib reduced and two patients discontinued treatment because of side effects, the researchers said the drug was generally well-tolerated.

Explore further: New models of kidney cancer may drive immunotherapy research

Journal reference: Journal of Clinical Oncology search and more info website

Provided by: Dana-Farber Cancer Institute

Read more at: https://medicalxpress.com/news/2017-06-drug-rare-advanced-kidney-cancer.html#jCp

Adventures with Human Growth Hormone

I’ve been dealing with Cushing’s since 1983.  The after effects of pituitary surgery since 1987, kidney cancer since 2006.  It’s time I felt better, already!

From 1999 to today,  not-so-quick recap from my bio:

1999 ~ Many people are now finding that they need HgH after pituitary surgery, so an Insulin Tolerance Test was performed. My endocrinologist painted a very rosey picture of how wonderful I’d feel on Growth Hormone. It sounded like a miracle drug to me!

I was only asked to fast before the ITT and to bring someone with me to take me home. There is no way I could have driven home. I got very cold during the test and they let me have a blanket. Also, though, lying still on that table for so long, my back hurt later. I’d definitely take – or ask for – a pillow for my back next time. They gave me a rolled up blanket for under my knees, too.

I don’t remember much about the test at all. I remember lying very still on the table. The phlebotomist took blood first, then tried to insert the IV (it took a few tries, of course). Then the endo himself put the insulin in through the IV and took the blood out of that. I remember the nurse kept asking me stupid questions – I’m sure to see how I was doing on the consciousness level. I’d imagine I sounded like a raving lunatic, although I believed that I was giving rational answers at the time.

Then everything just got black…I have no idea for how long, and the next thing I knew I was becoming aware of my surroundings again and the doctor was mumbling something. They gave me some juice and had me sit up very slowly, then sit on the edge of the table for a while. When I thought I could get up, they gave me some glucose tablets “for the road” and called my friend in. I was still kind of woozy, but they let her take me out, very wobbly, kind of drunk feeling.

My friend took me to a close-by restaurant – I was famished – but I still had trouble with walking and felt kind of dazed for a while. When I got home, I fell asleep on the sofa for the rest of the day.

But the most amazing thing happened. Saturday and Sunday I felt better than I had for 20 years. I had all this energy and I was flying high! It was so wonderful and I hoped that that was from the HgH they gave me to wake me up.

2001 ~ I had the ITT this morning. I don’t get any results until a week from Thursday, but I do know that I didn’t recover from the insulin injection as quickly as I did last time. The endo made a graph for my husband of me today and a “normal” person, although I can’t imagine what normal person would do this awful test! A normal person’s blood sugar would drop very quickly then rise again at about a right angle on the graph.

I dropped a little more slowly, then stayed very low for a long time, then slowly started to rise. On the graph, mine never recovered as much as the normal person, but I’m sure that I did, eventually.

The test this time wasn’t as difficult as I remember it being, which is good. Last time around, I felt very sweaty, heart pounding. I don’t remember any of that this time around. I do know that I “lost” about an hour, though. The phlebotomist took the first blood at 9:15, then the endo injected the insulin and took blood every 15 minutes after that. I counted (or remembered) only 4 of the blood draws, but it was 11:30 when they told me that my sugar wasn’t coming up enough yet and I’d have to stay another 30 minutes. It actually ended up being another hour.

Kim, the phlebotomist, asked me if I got a headache when they “crashed me” and I have no recollection of any of that.

Like last time, I was very, very cold, even with the blanket and my left arm – where the heplock was – fell asleep. Other than that – and my back hurting from lying on one of those tables all that time this wasn’t as bad as I remembered.

So, I waited for 10 days…

September 2004 ~ My new doctor was wonderful. Understanding, knowledgeable. He never once said that I was “too fat” or “depressed” or that all this was my own fault. I feel so validated, finally.

He looked through my records, especially at my 2 previous Insulin Tolerance Tests. From those, he determined that my growth hormone has been low since at least August 2001 and I’ve been adrenal insufficient since at least Fall, 1999 – possibly as much as 10 years! I was amazed to hear all this, and astounded that my former endo not only didn’t tell me any of this, he did nothing. He had known both of these things – they were in the past records that I took with me. Perhaps that was why he had been so reluctant to share copies of those records. He had given me Cortef in the fall of 1999 to take just in case I had “stress” and that was it.

The new endo took a lot of blood (no urine!) for cortisol and thyroid stuff. I’m going back on Sept. 28, 2004 for arginine, cortrosyn and IGF testing.

He has said that I will end up on daily cortisone – a “sprinkling” – and some form of GH, based on the testing the 28th.

October 2004 ~ I had cortrosyn and arginine-GHRH stimulation test at Johns Hopkins. They confirmed what the doctor learned from reading my 4 year old records – that I’m both adrenal-deficient and growth hormone-deficient. I started on my “sprinkle” (5 mg twice a day) of Cortef now and my new doctor has started the paperwork for GH so maybe I’m on my way…

November 2004 ~ Although I have this wonderful doctor, a specialist in growth hormone deficiency at Johns Hopkins, my insurance company saw fit to over-ride his opinions and his test results based on my past pharmaceutical history! Hello??? How could I have a history of taking GH when I’ve never taken it before?

Of course, I found out late on a Friday afternoon. By then it was too late to call my case worker at the drug company, so we’ll see on Monday what to do about an appeal. My local insurance person is also working on an appeal, but the whole thing sounds like just another long ordeal of finding paperwork, calling people, FedExing stuff, too much work when I just wanted to start feeling better by Thanksgiving. I guess that’s not going to happen, at least by the 2004 one.

As it turns out the insurance company rejected the brand of hGH that was prescribed for me. They gave me the ok for a growth hormone was just FDA-approved for adults on 11/4/04. The day this medication was approved for adults was the day after my insurance said that’s what is preferred for me. In the past, this form of hGH was only approved for children with height issues. Am I going to be a ginuea pig again? The new GH company has assigned a rep for me, has submitted info to the pharmacy, waiting for insurance approval, again.

December 2004 ~ I finally started the Growth Hormone last night – it’s like a rebirth for me. I look forward to having my life back in a few months!

January 2005 ~After a lot of phone calls and paperwork, the insurance company finally came through at the very last minute, just as I needed my second month’s supply. Of course, the pharmacy wouldn’t send it unless they were paid for the first month. They had verbal approval from the insurance, but the actual claim was denied. Talk about a cliff hanger!

Later January 2005 ~I’ve been on the growth hormone for 7 weeks now, and see no change in my tiredness and fatigue. A couple weeks ago, I thought there was a bit of improvement. I even exercised a little again, but that was short lived.

I feel like my stomach is getting bigger, and Tom says my face is looking more Cushie again. Maybe from the cortisone I’ve been taking since October. I can’t wait until my next endo appointment in March to increase my GH. I want to feel better already!

March 2005 ~ My IGF-1 was “normal” so I can’t increase the GH.

September 2005 ~ I don’t see any benefit with the growth hormone.

January 2006 ~A new year, a new insurance battle. Once again, they don’t want to pay so I have to go through the whole approval process again. This involves phone calls to Norditropin (the company that makes the GH), my endo, iCore Specialty Pharmacy (the people who prepare and ship the meds) and my insurance company. This is turning into a full-time job!

April 14, 2006 ~I just went to see my endo again on Thursday to see how things are. Although I know how they are – I’m still tired, gaining a little weight, getting some red spots (petechiae) on my midsection. He also noted that I have a “little” buffalo hump again.

My endo appointment is over. Turns out that the argenine test that was done 2 years ago was done incorrectly. The directions were written unclearly and the test run incorrectly, not just for me but for everyone who had this test done there for a couple years. My endo discovered this when he was writing up a research paper and went to the lab to check on something.

So, I’m off GH again for 2 weeks, then I’m supposed to be retested. The “good news” is that the argenine test is only 90 minutes now instead of 3 hours.

April 27, 2006 ~ Wow, what a nightmare my argenine retest started! I went back for that. Although the test was shorter, I got back to my hotel and just slept and slept. I was so glad that I hadn’t decided to go home after the test.

The next day I felt fine and drove back home, no problem. I picked up my husband for a biopsy and took him to an outpatient surgical center. While I was there waiting for the biopsy to be completed, I started noticing blood in my urine and major abdominal cramps. I left messages for several of my doctors on what I should do. I finally decided to see my PCP after I got my husband home.

When Tom was done with his testing, his doctor took one look at me and asked if I wanted an ambulance. I said no, that I thought I could make it to the emergency room ok – Tom couldn’t drive because of the anesthetic they had given him. I barely made it to the ER and left the car with Tom to park. Tom’s doctor followed us to the ER and became my new doctor.

They took me in pretty fast since I was in so much pain, and had the blood in my urine. They thought it was a kidney stone. After a CT scan, my new doctor said that, yes, I had a kidney stone but it wasn’t the worst of my problems, that I had kidney cancer. Wow, what a surprise that was! I was admitted to that hospital, had more CT scans, MRIs, bone scans, they looked everywhere.

My open radical nephrectomy was May 9, 2006, in another hospital from the one where the initial diagnosis was made. My surgeon felt that he needed a specialist from that hospital because he believed preop that my tumor had invaded into the vena cava because of its appearance on the various scans. Luckily, that was not the case.

My entire left kidney and the encapsulated cancer (10 pounds worth!) were removed, along with my left adrenal gland and some lymph nodes. Although the cancer (renal cell carcinoma AKA RCC) was very close to hemorrhaging, the surgeon believes he got it all. He said I was so lucky. If the surgery had been delayed any longer, the outcome would have been much different. I will be repeating the CT scans every 3 months, just to be sure that there is no cancer hiding anywhere. As it turns out, I can never say I’m cured, just NED (no evidence of disease). This thing can recur at any time, anywhere in my body.

I credit the argenine re-test with somehow aggravating my kidneys and revealing this cancer. Before the test, I had no clue that there was any problem. The argenine test showed that my IGF is still low but due to the kidney cancer I cannot take my growth hormone for another 5 years – so the test was useless anyway, except to hasten this newest diagnosis.

August 19, 2006 ~ I’ve been even more tired than usual now that I’m off GH.  But I also had cancer.

October 2006 ~ I went to see my Johns Hopkins endo again last week. He doesn’t “think” that my cancer was caused by the growth hormone although it may well have encouraged the tumor to grow faster than it would have.

I was so stupid way back in 1987 when I thought that all my troubles would be over when my pituitary surgery was over.

2016/2017 ~ So.  My 10 year kidney cancer anniversary passed, then 11.

May 4, 2017 ~ My endo at Hopkins and I talked about maybe trying growth hormone again.  We tested my levels locally and – surprise – everything is low, again.

So, we started the insurance routine again.  My insurance rejected the growth hormone I took last time around.  I just love how someone, a non-doctor who doesn’t know me, can reject my person endocrinologist’s recommendation.  My endo who specializes in Growth Hormone, who runs clinical trials for Johns Hopkins on “Control of growth hormone secretion, genetic causes of growth hormone deficiency, consequences of growth hormone deficiency.”

That insurance person has the power over the highly trained physician.  Blows my mind.

But I digress.  My doctor has agreed to prescribe Omnitrope, the insurance-guy’s recommendation.

June 14, 2017 ~ I got a call from my insurance.  They “may” need more information from my doctor…and they need it in 72 hours.

My doctor’s nurse says that they have to refer this to their pharmacy.

June 15, 2017 ~ I got a call from the Omnitrope folks who said they will need approval from my insurance company <sigh> but they will send me a starter prescription of 30 days worth.

June 16, 2017 ~ I got a call from the Specialty Pharmacy.  They’re sending the first month supply on Tuesday.  Estimated co-pay is $535 a month.  I may have to rethink this whole thing 😦   We sure don’t have an extra $6000.00 a year, no matter how much better it might make me feel.

June 19, 2017 ~ The kit arrived with everything but the actual meds and sharps.

June 20, 2017 ~ The meds and sharps arrived along with the receipt.  My insurance paid nearly $600 – and they took my copay out of my credit card for $533.

I still have to wait for the nurse’s visit to use this, even though I’ve used it in the past.

I’ve been doing some serious thinking in the last 24 hours.  Even if I could afford $533 a month for this, should I spend this kind of money on something that may, or may not, help, that may, or may not, give me cancer again.  We could do a couple cruises a year for this much money.  I’ve pretty much decided that I shouldn’t continue, even though I haven’t taken the first dose of this round.

What will happen?

Stay tuned!

Perioperative Systemic Therapy for Kidney Cancer: Current Data and Ongoing Trials

Kidney Cancer

 

Chicago, IL (UroToday.com) Dr. Uzzo gave the third and final talk in this excellent session highlighting systemic therapy in the management of kidney cancer. Focusing specifically on the role of perioperative systemic therapy (neoadjuvant [NAC] and adjuvant [AC]), he adeptly covered the prior literature and the future directions of this important intersection between surgery and systemic therapy. While his talk was extensive, below we will review the major highlights and key points.

Ultimately, in Dr. Uzzo’s eyes, we are all managers of health care risk. We seek to “understand, predict and prevent future health care events.” As such, from the time of diagnosis, the key steps in managing a patient are: identify risk (screening, etc), utilize risk tools to risk stratify, communicate this risk to the patient, and finally, mitigate risk with intervention.

Looking at biomarkers in the kidney cancer space, he highlights the key point that biomarkers have been few and far between for RCC. At the end of the day, commonly used biomarkers such as stage, grade, and histology still remain the standards for risk stratification. While numerous biomarkers (genetic, epigenetic, etc) have been evaluated, none have been demonstrated to be superior to stage, grade and histology. As biomarkers have failed to improve upon these factors, we also looked to different models to help stratify patients. In the localized RCC disease space, these include the UISS, MSKCC, SSIGN, and Mayo clinical models (among others) to predict recurrence, but the C-index for these tests ranged between 0.76-0.89. However, all the models shared common features that are easily identified clinically – stage, grade, tumor size, performance status, presentation, age, gender, and coagulative necrosis. Models for metastatic RCC are even less capable of predicting cancer-specific mortality (C-indices ~0.6). At this point, biomarkers and models give way to common patient and pathologic characterizations for risk stratification.

Neoadjuvant Therapy (NAT)
Dr. Uzzo provided a very nice comparison of the “Halstedian” model and “Fisheresque” model of cancer progression. Dr. Halsted, a legend in oncologic surgery, believed in stepwise progression of disease from stage 1 -> stage 2 -> stage 3 -> stage 4, which supported utilization of adjuvant therapy rather than NAT. However, Dr. Fisher was a strong proponent of the idea that a subset of patients were likely metastatic at inception, which better supported the need for NAC.

When looking at NAT, there are some key questions:

1) Does it work? (does it shrink the tumor? Can it work as a “litmus test” prior to cytoreduction? Can it control distant disease?)
2) Is it safe?
3) Are there translational signals?

In terms of tumor shrinkage, based on retrospective series and phase II trials, it results in approximately 25% tumor volume reduction, with an objective response rate (ORR) in 30-40% of patients. So, if patients are referred for that indication, that is what a medical oncologist can cite to a surgeon. However, the implications of this are heavily surgeon dependent, and as Dr. Uzzo states, it is a “function of judgment and experience” – if they feel that this will allow for partial resection vs. radical nephrectomy, or make a non-operative patient operative, then it may be worthwhile to proceed. This is difficult to quantify in clinical studies, and selection bias is an unavoidable issue. In his review of NAT to facilitate partial nephrectomy (PNx), there were <200 cases amongst 7 series.1 Similarly, there have primarily only been case reports/series demonstrating tumor thrombus reduction (25-40%), but rarely does it change the level of thrombus without a concomitant risk of toxicity.

In terms of efficacy, he reviewed a few clinical trials of neoadjuvant targeted therapies, including pazopanib.2 While many of these had some tumor size reduction, they often had high rates of patients not making it to surgery due to adverse events. Importantly though, a significant portion did not make it to surgery due to progression of extrarenal disease. As such, he emphasizes that NAT may be utilized as a litmus test for patient response. Patients progressing on NAT likely wouldn’t have benefited from surgery anyway.

No biomarkers have correlated with ORR in NAT trials.

In summary, NAT is not in the guidelines, high quality guidelines are limited, and there is no long-term data. While newer therapies (cabozantinib, immune checkpoint blockage) may change management, clinical trials are the recommendation for now.

Three clinical trials in NAT space:
CARMENA – activated in 2009, still accruing but having difficulty. Testing the importance of surgery – comparing surgery + adjuvant sunitinib vs. sunitinib alone.
SURTIME – testing sequencing (sunitinib -> surgery vs. surgery -> sunitinib). While initially expecting 440 patients, they have modified study to accrue 98 patients (study closed). In data analysis phase now.
ADAPT – SUO CTC joint effort, they have accrued 713/1133 patients in 3 years. Tests sequencing, including the use of autologous dendritic cell immunotherapy and sunitinib.

Adjuvant Therapy (AT)
Recent publications on adjuvant trials have increased interest in this treatment option. However, there are still no approved ATs for RCC. Dr. Uzzo breaks down the history of AT in RCC into three time periods: the “dark ages”, the “middle ages” and “the future.”

In the “dark ages” of AT, numerous trials were done but it combined “ineffective surgery with completely ineffective systemic therapy.” None of them showed significant benefit, though many had significant flaws.3

More recently, we have come into the “middle ages”, where we utilize “ineffective surgery with more effective systemic therapy.” As is well known, S-TRAC4 and ASSURE5, presented conflicting results regarding disease-free survival outcomes in the adjuvant setting. Dr. Uzzo did highlight the key differences in the studies (only cT3-4 disease in S-TRAC, primarily clear-cell histology in S-TRAC) that may have contributed to the discrepancy. However, even when the clear-cell subset of the ASSURE cohort was analyzed, there was no DFS benefit. Two ongoing trials for whom results are pending are PROTECT (pazopanib) and SORCE (sorafenib). The PROTECT trial investigators should be presenting their results later in the meeting.

He very nicely looked at the role of adjuvant therapy in other malignancies (breast cancer, colorectal cancer, melanoma and GIST) and found DFS benefit to be 4-11% (modest), often times with significant monthly cost. As such, he makes a good point, that adjuvant therapy touted as standard of care in other malignancies doesn’t have as much of a benefit as we often put faith in.

Adjuvant therapy is only marginally effect because of
1) Poor timing and patient selection
2) Bad biology
3) Ineffective therapies

In RCC, based on prior literature regarding growth kinetics, tumor doubling time, and presentation of metastatic disease, micrometastases typically present as visible disease between 6-11 years later. Perhaps we are not giving systemic therapy at the right time?

So, while it has not been shown to be highly effective in RCC yet, he recommends:
1) Improving timing (using CTCs and biomarkers)
2) Attacking tumor stem cells (yet to be identified)
3) Attack less promiscuous upstream targets (balance toxicity for specificity)

The future is promising. The “New” Age hopes to combine “incompletely effective surgery with potentially more effective systemic therapy.” He cites two trials, the ECOG PROSPER trial (nivolumab) and the SUO-CTC INmotion trial (atezolizumab), as upcoming studies with novel therapies that may provide new standards.

Overall, in terms of perioperative systemic therapy for RCC, there are no approved options. However, clinical trials with more effective therapies and better patient selection represent the future.

Presented By: Robert G. Uzzo, MD, FACS, Fox Chase Cancer Center, Philadelphia, PA

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting – June 2 – 6, 2017 – Chicago, Illinois, USA

From https://www.urotoday.com/conference-highlights/asco-2017/asco-2017-renal-cancer/96168-asco-2017-perioperative-systemic-therapy-for-kidney-cancer-current-data-and-ongoing-trials.html?utm_source=newsletter_4518&utm_medium=email&utm_campaign=asco-2017-day-2-highlights

Current Therapeutics of Kidney Cancer: Landmark Trials

 

Chicago, IL (UroToday.com) Dr. Vaishampayan provided an excellent walk down memory lane, highlighting the landmark trials in kidney cancer over the last 20 years at this morning’s ASCO 2017 annual meeting session “Evolving Treatment Paradigm in Renal Cell Carcinoma.”

 

Dr. Vaishampayan started by highlighting SEER data that suggests that although the incidence of kidney cancer has increased over the past 40 years, the mortality rates have essentially stayed the same over this time period. IL-2 has been approved for treatment of advanced RCC since 1992 and results of 255 patients who received high-dose IL-2 therapy demonstrated an objective response rate (ORR) of 14%, complete response (CR) rate of 5%, partial response (PR) rate of 9% [1]. Data from the PROCLAIMSM trial of 352 patients receiving targeted therapy prior to or following high dose IL-2 demonstrated 4% CR, 13% PR, 39% stable disease (SD), and 43% progressive disease (PD) with IL-2, demonstrating a clinical benefit for patients who progressed on targeted therapy [2]. Conclusions from these IL-2 studies include the fact that certain patients treated with IL-2 will have a CR+PR (~15%), however the majority of these patients are intermediate and not high risk. Furthermore, despite the toxicities of IL-2, they are predictable and manageable, and it is a remarkably time and cost effective therapy. Dr. Vaishampayan then highlighted that based on a meta-analysis of phase III trials of cytoreductive nephrectomy in the interferon era, patients derive a statistically significant survival benefit [3]. However, as Dr. Vaishampayan notes, based on recent SEER data, only 1/3 of patients receive cytoreductive nephrectomy.

The early to mid-2000’s saw the development of TKI therapy. In 2007, Escudier et al. demonstrated that sorafenib compared to placebo prolonged progression-free survival (PFS) in patients with advanced RCC [4]. Additional trials that year also demonstrated improved PFS for sunitinib compared to interferon-alfa [5], as well as temsirolimus compared to interferon alfa, particularly in patients with poor prognosis [6]. In 2013, we saw the COMPARZ trial of pazopanib vs sunitinib in the 1st line for mRCC, demonstrating comparable efficacy between the two agents (median OS: sunitinib 29.3 months vs pazopanib 28.4 months), although with improved tolerability with pazopanib [7].

There is currently a plethora of phase III trials for second line therapy for patients with mRCC that have reported in the past few years. In 2015, the METEOR trial (cabozantinib vs everolimus) reported that PFS was longer in the cabozantinib arm compared to everolimus (HR for death 0.67, 95%CI 0.51-0.89) [8]. A recent updated analysis of this data demonstrated improved OS, delayed disease progression, and improved ORR for cabozantinib [9]. Finally, Motzer and colleagues assessed lenvatinib + everolimus and lenvatinib alone and found that PFS for patients treated with combination therapy (HR 0.40, 95%CI 0.24-0.68) and lenvatinib alone (HR 0.61, 95%CI 0.38-0.98) was improved compared to everolimus alone [10].

In conclusion, there are many novel immune therapy trials on-going, but the landmark trials have established efficacy of multiple therapies in advanced RCC. As Dr. Vaishampayan notes, with multiple therapies available, a discussion of risk/reward ratio should occur with each patient. Certainly, we have hopes that single biomarker driven therapy may eventually be possible, however this is not currently available to ultimately guide precise treatment management.

Presented By: Ulka N. Vaishampayan, Karmanos Cancer Institute, Detroit, MI, USA

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

References:

1. Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995 Mar;13(3):688-696.
2. Clark JI, Wong MK, Kaufman HL, et al. Impact of sequencing targeted therapies with high-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients with Metastatic Renal Cell Carcinoma from an Ongoing Observational IL-2 Clinical Trial: PROCLAIMSM. Clin Genitourin Cancer 2017 Feb;15(1):31-41.
3. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004 Mar;171(3):1071-1076.
4. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):125-134.
5. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):115-124.
6. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med2007 May 31;356(22):2271-2281.
7. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013 Aug 22;369(8):722-731.
8. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015 Nov 5;373(19):1814-1825.
9. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in advanced renal cell carcinoma (METEOR): final results form a randomized, open-label, phase 3 trial. Lancet Oncol 2016 Jul;17(7):917-927.
10. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomized, phase 2, open-label, multicenter trial. Lancet Oncol 2015 Nov;16(15):1473-1482.

at the 2017 ASCO Annual Meeting – June 2 – 6, 2017 – Chicago, Illinois, USA

From https://www.urotoday.com/conference-highlights/asco-2017/asco-2017-renal-cancer/96167-asco-2017-current-therapeutics-of-kidney-cancer-landmark-trials.html?utm_source=newsletter_4518&utm_medium=email&utm_campaign=asco-2017-day-2-highlights

9 Tips For Safe Travel With Diabetes

Many of these tips work for Cushing’s patients on Growth Hormone, as well.

 

Traveling, whether it be for business or pleasure can easily take you out of your diabetes care routine. Before hightailing it out of town, make sure you are prepared. A little extra homework will help keep your diabetes from putting any kinks in your long-awaited travel plans.

How you prepare greatly depends on where you’re going and for how long. Ask yourself, how will your lifestyle change while traveling? Will you be able to prepare your own food, or will you be eating out? Will you be able to maintain adequate exercise or will you have more down time?

These helpful tips can help you stay on track with your diabetes treatment plan during your summer vacation getaways.

Read more here: 9 Tips For Safe Travel With Diabetes | MedicAlert Foundation