One of the dreaded complications of chemotherapy is Pulmonary fibrosis or interstitial pneumonitis which ultimately takes the patient's life when Complete Response may have been achieved. It is a dramatic event in the life of our patients, many survive and many have a limited fibrosis that allows life to go on after high doses of steroids. Some patients suffer consequences of exposure to high dose steroids. Suffice is to say that so far the Advisory committee has not called for any standard monitoring of this abnormal side effect, opting instead for a Head in the sand and crossing finger policy. Oncologists hide behind the statement that the "patient was warned this could happen". Knowing what we know, it is time to be rational about this and go after this side effect, understand it and monitor it carefully as we treat our patients!
So far repeated pulmonary function testing has been our recourse in patients who are taking Bleomycin. Those on Mitomycin, rarely do we give them a second dose...But when is comes to Gemzar for example, warning the patient that interstitial Pneumonitis could result, is all we do. It is unclear whether what happens in the lung with Bleomycin Vs Gemzar is the same phenomenon at various intensities. All we know is that the 2 phenomena both result in a limitation of lung function as a result of fibrosis. Studies have suggested that the early use of Growth factors to maintain the hematologic status of the patient may exacerbate or increase the frequency/occurrence of pulmonary fibrosis. In the treatment of Hodgkin disease, we try to avoid prompt use of growth factors to that end!
Fibrosis involves cyclins for sure, but no one has come forward to propose a clear Interleukin or other to be monitored as we treat our patients. The call for new bio-markers is therefore appropriate and pertinent! Something is happening in our patients at various levels, let's go and define it pronto instead of clinging to lingering politics of prayers, crossing the fingers and keeping our head in the sand !
Showing posts with label gemzar. Show all posts
Showing posts with label gemzar. Show all posts
Wednesday, August 21, 2013
Friday, April 26, 2013
CONSIDERATIONS IN RECURRENT OVARIAN CANCER TREATMENT:
Nice discussion by
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
By Anna Azvolinsky, PhD1
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
Study Finds Ovarian and Basal-Like/Triple-Negative Breast Cancers Genetically Similar
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
ONCOLOGY.
Vol. 27
No. 1
mTOR Inhibitors in the Treatment of Breast Cancer
By Shaveta Vinayak, MD, MS1,
Robert W. Carlson, MD1 |
January 15, 2013
1Department of Medicine, Stanford University School of Medicine, Stanford, California
ABSTRACT: The phosphatidylinositol 3-kinase/mammalian target
of rapamycin (PI3K/mTOR) pathway is commonly dysregulated in breast
cancer. In preclinical studies, hyperactivation of the PI3K pathway has
been linked to resistance to both endocrine therapy and trastuzumab(Drug information on trastuzumab)
(Herceptin). Rapalogs, agents that primarily inhibit mTOR-raptor
complex 1, have been studied in combination with endocrine therapy to
overcome endocrine resistance. Trials of combination endocrine therapy
and rapalogs in metastatic hormone receptor–positive breast cancer have
demonstrated variable results. However, two independent trials have
recently shown that combination everolimus (Afinitor) and tamoxifen(Drug information on tamoxifen) or combination everolimus and exemestane(Drug information on exemestane)
(Aromasin) is more effective than either endocrine agent alone. These
trials selected patients with cancer refractory to endocrine therapy,
which may be important in sensitizing tumors to inhibition of this
pathway. In human epidermal growth factor receptor 2 (HER2)-positive
breast cancer, the early clinical data with combinations of PI3K/mTOR
inhibitors and anti-HER2 therapies are encouraging.
| |
Sunday, March 10, 2013
(CONFERENCE CONTINUES) PANCREATIC CANCER UPDATE:
*FOLFIRINOX definitely in control as first choice for first line
but this option is too toxic in the elderly so a modified version is adopted by some
.*new IMPACT STUDY, GEMZAR-ABRAXANE is being rapidly adopted as an alternative to FOLFIRINOX for this same and very reason (Toxicity of Folfirinox)
This combination was reportedly tried in selected clinics (including Eastern Europe) in a Phase III trial, was tried against Gemzar alone
and gave Progression free survival of 5.5 months Vs 3.7 months
Overall survival 8.5 months Vs 6.7 months (Von Hoff DD et al.)
Abraxane given at 125 mg/m2 and Gemzar at 1000mg/m2 Q3/4 in the combination arm
----------------------------------------------------------------------------------------------
3rd choice of course was GEMZAR-ERLOTINIB follwed by GEMZAR ALONE.
===========================================================
NOTABLY NO TARGET THERAPY DISCUSSED WHICH NEEDS TO BE CORRECTED FAST!
but this option is too toxic in the elderly so a modified version is adopted by some
.*new IMPACT STUDY, GEMZAR-ABRAXANE is being rapidly adopted as an alternative to FOLFIRINOX for this same and very reason (Toxicity of Folfirinox)
This combination was reportedly tried in selected clinics (including Eastern Europe) in a Phase III trial, was tried against Gemzar alone
and gave Progression free survival of 5.5 months Vs 3.7 months
Overall survival 8.5 months Vs 6.7 months (Von Hoff DD et al.)
Abraxane given at 125 mg/m2 and Gemzar at 1000mg/m2 Q3/4 in the combination arm
----------------------------------------------------------------------------------------------
3rd choice of course was GEMZAR-ERLOTINIB follwed by GEMZAR ALONE.
===========================================================
NOTABLY NO TARGET THERAPY DISCUSSED WHICH NEEDS TO BE CORRECTED FAST!
Saturday, March 9, 2013
RECURRENT LIPOSARCOMA
The other day we were in a conference discussing a case of Liposarcoma. The man was in his 50ies and had been referred to the University surgeon for an extensive abdominal Liposarcoma that needed further resection. The disease had been resected at least twice by the community surgeon before, it had returned with significant peritoneal and pelvic infiltration. Interval between resections had been in years, but now it was in months. Clearly, the disease has packed further gene abnormalities now that it is evidently metastatic. Let me take this back, because despite the widespread invasion in the abdomen, there was no tissue invasion. There were no clear liver, lung or brain invasion. This disease was killing a man before our eyes because of clear infiltration of abdominal tissues.
Because of the interval between surgeries, the Oncologist argued that this is a low grade tumor and may not be handled with standard chemotherapy and I strongly believe he was right. My case with Angiosarcoma did not budge with Gemzar, Taxol followed by MAID, I am trying AVASTIN ALONE now!
But returning to the case, the hospital and the surgery department are now breathing on the neck of the surgeon because they do not see the point of putting the patient through very expensive surgeries followed by costly ICU stays every few months. I guess there are potential liabilities linked to the exercise. Particularly because the surgeries were done when this patient was with evident big progression of disease, but asymptomatic still. Oncologist and Surgeon alike argued we should not wait for symptoms, because it could be inoperable by then, and an aggressive surgery plan is helpful in these local diseases.
With standard chemotherapy out the only thing left is Target therapy as an effective option. We did not get help from the pathology department since no genetic abnormality testing is done (this is not Mayo or Harvard. DR KRIS who speaks of gene panels in lung cancer does not live here). And Votrient, the only FDA approved drug is indicated in those who failed chemotherapy. Basically, you have to put this man on chemotherapy that you know will harm him unnecessarily in order to get to Votrient (Pazopanib), an anti-VEGFR(s), Anti-c-KIT, anti-PDGFR a/Beta. with 3-4 months advantage over placebo.
-------------------------------------------------------------------------------------------
Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Votrient for advanced soft tissue sarcoma
The U.S. Food and Drug Administration today approved Votrient (pazopanib) to treat patients with advanced soft tissue sarcoma who have previously received chemotherapy. Soft tissue sarcoma is a cancer that begins in the muscle, fat, fibrous tissue, and other tissues.
Votrient is a pill that works by interfering with angiogenesis, the growth of new blood vessels needed for solid tumors to grow and survive.
A rare cancer with many subtypes, soft tissue sarcoma occurs in about 10,000 cases annually in the United States. More than 20 subtypes of sarcoma were included in the clinical trial leading to approval of Votrient. The drug is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors.
“Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas.”
The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The study was designed to measure the length of time a patient lived without the cancer progressing (progression-free survival). The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.
The most common side effects in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.
Votrient carries a boxed warning alerting patients and health care professionals to the potential risk of liver damage (hepatotoxicity), which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines.
Votrient was granted an orphan drug status designation for this indication. An orphan designation is given to a drug intended to treat a disease affecting fewer than 200,000 patients in the United States. Votrient was first approved in October 2009 for the treatment of advanced kidney cancer.
Votrient is marketed by GlaxoSmithKline of Research Triangle Park, N.C.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Because of the interval between surgeries, the Oncologist argued that this is a low grade tumor and may not be handled with standard chemotherapy and I strongly believe he was right. My case with Angiosarcoma did not budge with Gemzar, Taxol followed by MAID, I am trying AVASTIN ALONE now!
But returning to the case, the hospital and the surgery department are now breathing on the neck of the surgeon because they do not see the point of putting the patient through very expensive surgeries followed by costly ICU stays every few months. I guess there are potential liabilities linked to the exercise. Particularly because the surgeries were done when this patient was with evident big progression of disease, but asymptomatic still. Oncologist and Surgeon alike argued we should not wait for symptoms, because it could be inoperable by then, and an aggressive surgery plan is helpful in these local diseases.
With standard chemotherapy out the only thing left is Target therapy as an effective option. We did not get help from the pathology department since no genetic abnormality testing is done (this is not Mayo or Harvard. DR KRIS who speaks of gene panels in lung cancer does not live here). And Votrient, the only FDA approved drug is indicated in those who failed chemotherapy. Basically, you have to put this man on chemotherapy that you know will harm him unnecessarily in order to get to Votrient (Pazopanib), an anti-VEGFR(s), Anti-c-KIT, anti-PDGFR a/Beta. with 3-4 months advantage over placebo.
-------------------------------------------------------------------------------------------
FDA NEWS RELEASE
For Immediate Release: April 26, 2012Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Votrient for advanced soft tissue sarcoma
The U.S. Food and Drug Administration today approved Votrient (pazopanib) to treat patients with advanced soft tissue sarcoma who have previously received chemotherapy. Soft tissue sarcoma is a cancer that begins in the muscle, fat, fibrous tissue, and other tissues.
Votrient is a pill that works by interfering with angiogenesis, the growth of new blood vessels needed for solid tumors to grow and survive.
A rare cancer with many subtypes, soft tissue sarcoma occurs in about 10,000 cases annually in the United States. More than 20 subtypes of sarcoma were included in the clinical trial leading to approval of Votrient. The drug is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors.
“Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas.”
The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The study was designed to measure the length of time a patient lived without the cancer progressing (progression-free survival). The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.
The most common side effects in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.
Votrient carries a boxed warning alerting patients and health care professionals to the potential risk of liver damage (hepatotoxicity), which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines.
Votrient was granted an orphan drug status designation for this indication. An orphan designation is given to a drug intended to treat a disease affecting fewer than 200,000 patients in the United States. Votrient was first approved in October 2009 for the treatment of advanced kidney cancer.
Votrient is marketed by GlaxoSmithKline of Research Triangle Park, N.C.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
#
,
-------------------------------------------------------------------------------------
For the sake of argument
1. In this man we know it is a Liposarcoma
therefore the primary deficiency is in the handling of lipid. Insulin Receptor, may be? IGFR, IGFBP, PPR1. CCR11
(GOT TO RUN TO CONFERENCE WITH XCENDA IN CHICAGO---TO BE CONTINUED!)
(GOT TO RUN TO CONFERENCE WITH XCENDA IN CHICAGO---TO BE CONTINUED!)
-
Sunday, November 25, 2012
SEARCHING FOR A CANCER CURE
At CRBCM we believe that CPRIT is our necessary path to Victory over Cancer.
We also know we will not get its help this time around, not because we do not deserve the help but frankly because it is distracted. Science is an objective thing. It is a race. You have the right move, the right stuff, you win, no matter where you come from. It is the Olympics without steroids.
We at CRBCM have understood one thing, in the race for the cure, harnessing the force and laws of nature has an unparalleled advantage. Forcing a cell to die can be done by telling and convincing it to die. Or blasting it and crossing our fingers and hoping it will die. Chemotherapy did this mostly the second way but its success was partial. Chemotherapy only works when it manages to finally talk the language. Indeed, some chemotherapy manages to reach the syllables of the cellular language of death.
Sorting through the maze of messages, 2 powerful set of syllables come out:
1. That if it fails to repair broken DNA and therefore does not perform GENE REPAIR, this fact will automatically activate your P53 leading to an automatic stop of the cell into its cycle division. There is no loophole to this principle unless the P53 is abnormal. Knowing this is powerful. Now we understand why Cisplatin (and to some extent Gemcitabine) is a powerful drug because it disrupts the DNA structure. We also understand that cells with rapid repair of DNA, will brush it off, literally.
2.with further proof of principle, we believe that there is a second automatic message or syllables.
Destruction of Microfilaments (and therefore secondarily Microtubules in general) during cell division, leads to an automatic release of Caspase from the Mitochondria no matter what (and this is what includes the BCL-2 protection). It is in this law that resides the strength of Taxanes. Medication that works even in resistant diseases such as Melanoma where Abraxane has a role. Taxanes' limitations appear to be in the type of microtubules attacked. Medication that attacks Microfilament of the type involved in cell divison, where the Centromere is attached, appears to send a more determinant trigger to Caspase release. This is where our interest comes in the Anti-kinesin. We believe and predict that an effective anti-kinesin drug in combination with Taxane and Cisplatin/gemzar based combination, will harness best this law. They will prove to be effective in cure because they will be effective in both treatment and maintenance settings. This is also why the combination of Gemzar and Taxol has proven to be the strongest non platinum combination.
Following this principle, we believe now at CRBCM, that target therapy not following the laws of nature will have only 20-30% response rate, meaning effective in only the cells that lack loophole mechanisms. (this also means because of phenotype heterogeneity, 70-85% of cells have potentially intrinsic loophole to any signal transduction target stimulation or blockage).
Lets keep our eyes on the ball, do not invest in stuff they are throwing at you! More to come...
At CRBCM we believe that CPRIT is our necessary path to Victory over Cancer.
We also know we will not get its help this time around, not because we do not deserve the help but frankly because it is distracted. Science is an objective thing. It is a race. You have the right move, the right stuff, you win, no matter where you come from. It is the Olympics without steroids.
We at CRBCM have understood one thing, in the race for the cure, harnessing the force and laws of nature has an unparalleled advantage. Forcing a cell to die can be done by telling and convincing it to die. Or blasting it and crossing our fingers and hoping it will die. Chemotherapy did this mostly the second way but its success was partial. Chemotherapy only works when it manages to finally talk the language. Indeed, some chemotherapy manages to reach the syllables of the cellular language of death.
Sorting through the maze of messages, 2 powerful set of syllables come out:
1. That if it fails to repair broken DNA and therefore does not perform GENE REPAIR, this fact will automatically activate your P53 leading to an automatic stop of the cell into its cycle division. There is no loophole to this principle unless the P53 is abnormal. Knowing this is powerful. Now we understand why Cisplatin (and to some extent Gemcitabine) is a powerful drug because it disrupts the DNA structure. We also understand that cells with rapid repair of DNA, will brush it off, literally.
2.with further proof of principle, we believe that there is a second automatic message or syllables.
Destruction of Microfilaments (and therefore secondarily Microtubules in general) during cell division, leads to an automatic release of Caspase from the Mitochondria no matter what (and this is what includes the BCL-2 protection). It is in this law that resides the strength of Taxanes. Medication that works even in resistant diseases such as Melanoma where Abraxane has a role. Taxanes' limitations appear to be in the type of microtubules attacked. Medication that attacks Microfilament of the type involved in cell divison, where the Centromere is attached, appears to send a more determinant trigger to Caspase release. This is where our interest comes in the Anti-kinesin. We believe and predict that an effective anti-kinesin drug in combination with Taxane and Cisplatin/gemzar based combination, will harness best this law. They will prove to be effective in cure because they will be effective in both treatment and maintenance settings. This is also why the combination of Gemzar and Taxol has proven to be the strongest non platinum combination.
Following this principle, we believe now at CRBCM, that target therapy not following the laws of nature will have only 20-30% response rate, meaning effective in only the cells that lack loophole mechanisms. (this also means because of phenotype heterogeneity, 70-85% of cells have potentially intrinsic loophole to any signal transduction target stimulation or blockage).
Lets keep our eyes on the ball, do not invest in stuff they are throwing at you! More to come...
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