Tuesday, April 16, 2013

A Concise Guide for Sutent User Newbies (new users) | Cancer Survivors Network

Here's a good beginning guide to Sutent.  It's geard toward kidney cancer patients, but it's also good advice for those of us using Sutent for other cancers.



A Concise Guide for Sutent User Newbies (new users)

Eliezer2
Posts: 34 
Joined: Aug 2012 
A Concise Guide for Sutent User Newbies (new users)


*  Sutent does not "work" for everyone, but it does work for a LOT of people.  No one knows for how long it can work because it has only been on the market for a few years.

*  I have stage 4 RCC with a lot of small mets in my lungs.  I am one of the people for whom Sutent works and I recommend it!  I am not getting any kickbacks for saying so from the manufacturer (alas).  I have been on it for about 19 months.

*  At this point the disease itself is not directly causing me any disruption, discomfort, or pain.  Any discomfort I have is not directly from the disease but from the side effects of the Sutent.  The price for halting the progression of the disease is those side effects.  These vary a lot across patients and even for individual patients across Sutent cycles.  The side effects are not trivial, but generally not so bad as to prevent normal functioning and quality of life (at least by my experience).  Coping with cancer at this point is simply coping with those side effects, but nothing worse than that.

*  The side effects of Sutent vary from the mild to the very annoying.  They also vary from the medically irrelevant to the medically potentially dangerous.

Side Effects:

*  I find that they are milder on a two-week-on-one-week-off cycle than the 4-2 week version.  I am on the full monty, the 50 mg dose, which some people cannot tolerate.  I think you are better off on 50 mg with shorter cycles than 37.5 with longer cycles.

*  I think the two common and most dangerous potentially for most people are high blood pressure and slow thyroid functions.  There are some people who experience disruption of liver functions or heart functions; one needs to keep an eye on those things.   Blood pressure and slow thyroid issues are relatively easy to treat and control but are dangerous if not controlled.  Simple blood pressure meds work for me and I go off them when I am on the breaks in the Sutent cycle.  Slow thyroid gets fixed with a thyroid supplement that has no other side effects.  My thryoid has gotten slower and slower and I have had to adjust the thyroid supplement accordingly, but nothing worse than that.  Slow thyroid and high blood pressure are actually a mixed BLESSING, because they are highly correlated with the Sutent being EFFECTIVE!

*  Mildly annoying side effects:

    -  MANY people get mouth, hand, feet sores.  I have gotten none, but I think my experience is not typical.  I understand these are manageable.

   -  Taste changes in mouth late in cycle - spicy foods, salty, alcohol, mouth wash are very irritating when this happens.   Taste changes are milder on a 2-1 cycle compared with 4-2.

   -  General muscle weakness in arms and legs late in the cycle, disappears during Sutent break.  These are also milder on 2-1 cycle compared with 4-2.  Just take stairs slower and carry fewer groceries.

     -  I get watery eyes late in cycle.  Nothing to do about it.

     -  My body temp drops quite low and I feel cold a lot.  Drops to 35 degrees C (94.8 F).  Might be thyroid related, or not.  Nothing to do but turn up the thermostat and add layers.

    - General feelings of tiredness and fatigue.  Fixed by taking naps. 

    - Hemoglobin can drop.  Fix by taking iron supplement.  Blood fats (cholesterol and triglycerides) can shoot up, partly because of thyroid.  Adjust diet and, if necessary, take a pill that knocks them back down.

  -  Hair turning white and skin pale.  I do not care much about this (on male geezers it is supposed tolook distinguished) but women patients complain a lot about it.  Can cure it with hair color.   My skin is a little dry, including in some unmentionable spots, but nothing some skin cream or Vaseline cannot fix.

*  Very annoying side effects:

   - For me, the only really serious annoyance has been gastro side effects:  the "runs," painful gas, cramps, sometimes nausea.  I have been wrestling with finding ways to control this for over a year and a half.  Most people seem to control it more easily than me, but what they use has not helped me.  This past month I have tried a couple of new things and at long last they seem to be working.  For me, this has been the major factor negatively impacting quality of life, but really the only such factor.


*   Emotional side:  This of course also varies widely across people.  I was pretty scared and stressed in the first few weeks after I discovered I had mets in lungs and was Stage 4, rather than Stage 1.  After that, I made my peace with it and I would say that at this point I am not affected emotionally at all, am as chipper and optimistic as healthy people my age (I am 62).  I live a normal life, work, do pretty much all the things that healthy guys my age do, minus the jogging and weight lifting.  When I was first diagnosed, I was sent by the oncologists to a social worker for counseling.  She invited me into her office with boxes of tissues, since so many people sit and cry there under the circumstances.  I ended up telling her jokes and picking up HER spirits.  I am not depressed, I am no moodier than before I got cancer.  I do not feel dread on a day-to-day basis.  My most distressing experiences are all gastro side effects.   I am somewhat religiously observant but I do NOT think my emotional state has anything to do with that.

*  I have LOTS of small mets in my lungs.  I can also do 30 pushups at age 62 (how many healthy blokes my age can say that?) and my pulmonary functioning levels are those of a health 45 year old (how many healthy blokes my age can say that?).  I do get out of breath more easily, but I attribute that to cutting back on exercise when I turned Stage 4.

* I do still get a bit nervous when waiting for results from CT's and similar, and I have put my financial affairs in order, just in case.  But at age 62, EVERYONE should do THAT.  Once put in order, I ignore the subject altogether and get on with enjoying life. 

*  Do things you like to do and that give you pleasure.  There is life after RCC!



Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer — NEJM

Now this sounds interesting!  I hope the study is expanded.


BACKGROUND

Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium–iodide symporter and uptake of iodine. Their effects in humans are not known.

METHODS

We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.

RESULTS

Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients withBRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.

CONCLUSIONS

Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.)
Supported by grants from the American Thyroid Association, the Society of Memorial Sloan-Kettering Cancer Center, the National Institutes of Health (RO1-CA50706 and RO1-CA72598), AstraZeneca, and Genzyme, as well as funding from the Lefkofsky Family, Margot Rosenberg Pulitzer, Byrne, and J. Randolph Hearst foundations. The iodine-124 PET studies were supported in part by a grant from the In-Vivo Cellular and Molecular Imaging Center (P50 086438-10). Dr. Domínguez was supported in part by a grant from Pontificia Universidad Católica de Chile and Becas Chile (76100021), and Dr. Deandreis by a grant from Fondation de France (2010-12521).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the research study staff, particularly Susan Korte, Alex F. Mak, Brynna Lipson, Donna Lisa, and Lisa Cox, R.N.

SOURCE INFORMATION

From the Head and Neck Oncology Service (A.L.H., E.J.S., D.G.P.) and the Endocrinology Service (R.L., R.M.T., J.A.F.), Department of Medicine, and the Departments of Radiology (R.K.G., D.D., S.H., S.G., S.M.L.), Medical Physics (K.S.P., P.B.Z.), Pathology (R.A.G.), and Human Oncology and Pathogenesis (J.C.R.-F., J.M.D., J.A.F.), and the Epidemiology–Biostatistics (R.S.) and Molecular Pharmacology and Chemistry (S.M.L.) Programs, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York.
Address reprint requests to Dr. Fagin at the Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065.

TROVAGENE :: TROVAGENE :: Revolutionary Molecular Diagnostics


Trovagene to Study Transrenal BRAF Mutations in Primary and Metastatic Cancers

1/3/2013
Study with MD Anderson will compare detection of BRAF mutations in urine to biopsy samples, and monitor therapeutic response, outcomes
 
SAN DIEGO, January 3, 2013 -- Trovagene, Inc. (NASDAQ: TROV), a developer of transrenal molecular diagnostics, announced that it has entered into a clinical collaboration with The University of Texas MD Anderson Cancer Center to detect transrenal BRAFmutations in the urine of patients with advanced or metastatic cancers.

Researchers will use Trovagene’s proprietary transrenal DNA (TrDNA) detection technology to evaluate BRAF mutation status in urine as compared to tissue biopsy. The study also calls for monitoring of mutation levels in the urine at planned intervals during and after treatment to assess outcomes including: response rate (RR); stable disease (SD); progression-free survival (PFS); and overall survival (OS). Results from patients who receive therapy that reflects their BRAF mutation status (e.g., BRAF inhibitors, MEK inhibitors) will be compared to outcomes for patients who receive standard-of-care therapy regardless of mutation status.

According to recent estimates, BRAF mutations are present in more than 20% of all cancers, and in 40% and 43% of all thyroid and skin cancer samples, respectively1. Several targeted therapies for BRAF-mutated melanomas are already on the market and in development, including BRAF inhibitors vemurafenib (Zelboraf®) and dabrafenib; and trametinib, a MEK inhibitor.

 “One of the  potential benefits of TrDNA would be its utility as a systemic, liquid biopsy, providing real-time information that may help guide targeted therapy decisions, and then help clinicians more easily monitor a patient’s therapeutic response and disease state,” said Filip Janku, MD, PhD, principal investigator for the study at MD Anderson. “A urine-based assay that reliably and cost-effectively detects mutations would be extremely useful as an aid in personalized medicine.”

"This study represents a first-of-its kind look at how urine-based mutation detection can be used to track patients from initial diagnosis through therapy, and then to monitor for early signs of progression,” said Dr. Charlie Rodi, chief technology officer at Trovagene. “We are pleased to sponsor this study with MD Anderson, and look forward to learning more about the unique properties and clinical utilities of our transrenal mutation assays.”

1.   Prevalence of BRAF mutations in various cancers. Sanger COSMIC site.http://cancer.sanger.ac.uk/cosmic/gene/overview?ln=BRAF


About Trovagene, Inc.
Headquartered in San Diego, California, Trovagene is developing its patented technology for the detection of transrenal DNA and RNA, short nucleic acid fragments, originating from normal and diseased cell death that cross the kidney barrier and can be detected in urine.  Trovagene is leveraging its intellectual property in oncogene mutations via out-licensing and use of its transrenal technologies to extend oncogene mutation detection using urine as a sample.  As a non-invasive and abundant sample, urine may overcome many of the cost and collection challenges associated with biopsy, as well as the volume limitations of blood.

Trovagene has a strong patent position as it relates to transrenal molecular testing. It has U.S. and European patent applications and issued patents that cover testing for HPV and other infectious diseases, cancer, transplantation, prenatal and genetic testing. In addition, it owns worldwide rights to nucleophosmin-1 (NPM1), an informative biomarker for acute myelogenous leukemia (AML) and mutations in the SF3B1 gene, which have been shown to be associated with chemotherapy response in chronic lymphocytic leukemia (CLL) patients, as well as other hematologic malignancies.

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimated" and "intend," among others. These forward-looking statements are based on Trovagene's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any medical diagnostic tests under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful or that any product will receive regulatory approval for any indication or prove to be commercially successful. Trovagene does not undertake an obligation to update or revise any forward-looking statement.  Investors should read the risk factors set forth in Trovagene's Form 10-K for the year ended December 31, 2011 and other periodic reports filed with the Securities and Exchange Commission.

Contacts
Trovagene, Inc.
Keith McCormick
VP, Commercial Operations
+1 (858) 952-7640
kmccormick@trovagene.com
http://www.trovagene.com

Monday, April 15, 2013

Cancer-Related Fatigue Often Overlooked, Study Finds

Man, is this ever true!  Unless you have an oncologist who has been through chemo, I don't think they understand what a problem fatigue is.



Cancer-Related Fatigue Often Overlooked, Study Finds

health day
Doctors should address helpful behaviors, treatments, researchers sayTHURSDAY, Dec. 27 (HealthDay News) -- Too few cancer patients receive care for debilitating fatigue that can last for months or even years after treatment, a new study finds.
"Fatigue is a factor that not only significantly diminishes quality of life but is also associated with reduced survival," study author Dr. Andrea Cheville, a physiatrist with the Mayo Clinic Department of Physical Medicine and Rehabilitation, said in a clinic news release.
The study, published in the January issue of the journal Supportive Care in Cancer, included 160 lung, breast, colon and prostate cancer patients who had moderate to severe fatigue. They were asked if their oncology teams had mentioned any of the cancer fatigue treatments recommended by the National Comprehensive Cancer Network, such as counseling, medications and getting more exercise.
Only 10 percent of patients said they were told to get more exercise or to try other non-medication ways of reducing fatigue. More than 35 percent of the patients were offered sleep medications, even though drugs have been shown to be the least effective way to treat fatigue in cancer patients.
The researchers also found that the type of cancer was a factor in whether patients received treatment for fatigue. Only 15 percent of colon cancer patients and 17 percent of prostate cancer patients received treatment for fatigue, while 48 percent of breast cancer patients were told about counseling.
"We found the vast majority of patients were not engaging in behavioral practices that could reduce fatigue and potentially enhance quality of life," Cheville said. "And almost a third reported napping during the day, which can actually worsen fatigue."
"We could be doing a much better job addressing fatigue, with more reliable instruction for patients and offering treatments that have been shown to work," she said.
Oncologists, however, may not have the time or resources to deal with patients' quality-of-life issues. There may be a need for specialists who focus on helping cancer patients deal with issues such as fatigue, depression and pain, the researchers said.
More information
The U.S. National Cancer Institute has more about fatigue in cancer patients.
SOURCE: Mayo Clinic, news release, Dec. 18, 2012
Copyright © 2012 HealthDay. All rights reserved.

Vandetanib given for advanced differentiated thyroid cancer almost doubles progression free survival


Sounds interesting, hope it leads somewhere!


Results of a phase 2 randomised trial for patients with advanced differentiated thyroid cancer (DTC) show that those treated with the oral targeted agent vandetanib survived without the disease getting worse for almost twice as long as patients given placebo (11.1 months vs 5.9 months). The findings, published Online First in The LancetOncology, are the first to show clear evidence of prolonged progression free survival (PFS) with a targeted agent for advanced DTC, a disease for which no effective treatment exists.
Over the past decade, the incidence of thyroid cancer has more than doubled worldwide. Recently, multi-targeted kinase inhibitors have emerged as promising treatments for DTC, but until now, no placebo-controlled studies have been done.
Here, Martin Schlumberger from the Institut Gustave Roussy in France and colleagues aimed to establish whether vandetanib, a drug that targets three proteins known to play a key role in the growth and spread of thyroid cancer—endothelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and RET (REarranged during Transfection) protooncogene—would impact PFS and overall survival (OS).
The study randomly assigned 145 late-stage or advanced DTC patients from seven European countries to either 300 mg/day of vandetanib (72 patients) or placebo (73).
Compared with placebo, vandetanib was associated with significantly improved PFS of 11.1 months compared with 5.9 months. At 6 months, patients treated with vandetanib also had a significantly better disease control rate (DCR; which includes complete and partial responses and stable disease) than those given placebo. However, no significant difference in OS was noted between the groups.
Interestingly, patients with the more common papillary thyroid cancer (PTC) experienced more prolonged PFS (median PFS 16.2 months) than patients with either FTC or differentiated carcinoma (median PFS 7.7 months).



Patients who received vandetanib experienced much greater toxicities, in particular increased QTc prolongation (the lengthening of a specific interval of time in the heart's electrical cycle that can lead to death), diarrhoea, asthenia (weakness), and fatigue. Two treatment-related deaths also occurred in the vandetanib group.
According to Schlumberger, “These results are potentially good news for patients with aggressive DTC who currently have few treatment options. The significant improvements in PFS and DCR versus placebo suggest that vandetanib may be an effective treatment option for long-term stabilization of advanced DTC, particularly for patients with PTC.”
In a linked Comment, Keith Bible from the Mayo Clinic, Rochester, USA says, “Despite providing important additional evidence about the clinical activity of vandetanib in DTC, [the study] leaves the important issue of the effect of vandetanib on overall survival unresolved.”
He adds, “More work is needed to better clarify which patients with DTC might have the greatest net benefits from kinase inhibitors…and to develop individualised treatment approaches in DTC.”

Emerging role of multikinase inhibitors for refractory thyroid cancer


Just an abstract, but interesting.


Emerging role of multikinase inhibitors for refractory thyroid cancer



Review

(1994) Total Article Views


Authors: Perez CA, Arango BA, Velez M, Raez LE, Santos ES

Published Date August 2012 Volume 2012:6 Pages 257 - 265
DOI: http://dx.doi.org/10.2147/BTT.S24465

Cesar A Perez,1 Belisario A Arango,1 Michel Velez,1 Luis E Raez,2 Edgardo S Santos1
1University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, USA; 2Memorial Cancer Institute, Memorial Health Care System, Hollywood, FL, USA

Abstract: Thyroid cancer incidence continues to increase, remaining the most common endocrine malignancy. The need for effective systemic therapies combined with high incidence of driver mutations and overexpression of molecular pathways make refractory thyroid cancer an ideal candidate for treatment with novel agents. Multikinase inhibitors have caused a paradigm shift in the treatment of patients with advanced iodine-refractory thyroid cancer. These agents have shown to be the most effective systemic therapy for this disease not only causing prolonged responses but also improving survival. The activity of these agents inhibiting several pathways simultaneously, such as rearranged during transfection protooncogene, mitogen-activated protein kinase, and angiogenesis, can probably explain the effectiveness in controlling the progression of this malignancy. Several of these agents are currently on clinical studies in patients with differentiated and medullary thyroid cancer and most of them are showing promising clinical activity. With the approval of vandetanib for the treatment of medullary thyroid cancer, a new era in the management of this disease has begun. The molecular rationale for the use of these drugs for thyroid cancer is discussed as well as their promising clinical results.

Keywords: axitinib, cabozantinib, lenvatinib, mitogen-activated protein kinase (MAPK), motesanib, pazopanib, thyroid cancer, vandetanib, vascular endothelial growth factor receptor-2 (VEGFR2)