The Adams Trial
Trials and Treatment.
London St.Barts Trial.
Dr Peter Szlosarek MD, PhD Centre: Molecular Oncology Fellowships: Clinical Research Fellowship (CRUK)Clinician Scientist Fellowship (CRUK)
Job Title: Clinical Senior Lecturer Email: p.w.szlosarek@qmul.ac.uk QMUL Directory Research Interests Dr Peter Szlosarek's main research themes are in Lung Cancer/Mesothelioma, Ovarian Cancer, Senior Researcher and Skin Cancer/Melanoma
Arginine, a semi-essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome. In addition to protein synthesis, arginine is involved in diverse aspects of tumour metabolism, including the synthesis of nitric oxide, polyamines, nucleotides, proline and glutamate. However, several tumours, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer, are unable to produce arginine, due to variable loss of the enzyme argininosuccinate synthetaseASS1 which is necesary for L-arginine synthesisis. Our lab is exploring why ASS1 is aberrantly expressed in human cancers. We have identified methylation-dependent silencing of ASS1 in several tumours, including mesothelioma, ovarian cancer and lymphoma, that are sensitive to arginine deprivation. We are now testing whether the ASS1-deficiency of mesothelioma may be exploited using the arginine-lowering agent, pegylated arginine deiminase (ADI-PEG20). Several phase I/II clinical trials of pegylated arginine deiminase have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1-negative tumours.
Preclinical work in the area of arginine degradation is ongoing in several cancers with our national and international collaborators and industry. We are studying the regulation and modulation of ASS1 expression and the role of the proinflammatory microenvironment in arginine auxotrophic cancers, with the long-term aim of developing novel therapeutic strategies incorporating arginine deprivation and ASS1 loss into routine oncological practice.
We continue to study the links between inflammation and metabolism to discover novel therapeutic targets in oncology.
Profile I graduated in 1994 from King’s College, London with degrees in Pharmacology, Medicine and Surgery, receiving the Pharmacology and Therapeutics Intercalated BSc Prize and Legg Prize in Surgical Pathology.
I obtained the MRCP in 1997, and subsequently trained in medical oncology at St. George's, Guy’s and St. Bartholomew's Hospitals, completing a PhD on the molecular biology of TNF- in ovarian cancer and a postdoctoral position in the Centre for Cancer and Inflammation under Prof Balkwill in 2005.
After a substantive NHS oncology consultant post, I rejoined the BCI as a Principal Investigator in 2008. My translational lab program focuses on aberrant tumour metabolism and inflammation and is closely allied to my clinical interests in the treatment of mesothelial, lung and skin cancers.
***
Maidstone Trial.
Phase 3 NGR-hTNF
30 October 2011 an Update.I was the 2nd to sign up for this trial. But because the patient before me has dropped out I am now the First patient in the Trial and followed by a man who is a week behind me.
This is The Trial That Mavis started on Thursday 13th October 2011This has really been a very interesting day.
We walked Louis and then came home and rung the hospital to let them know we were coming up today so they could make the Trial Drug up, this was what I was asked to do. But, they had no notes on me so I rang the Trial Nurse and she sorted it for me and said would I phone when we are on the M2 this is because the Drug cant sit around.
So I did that as we were on the M2 and arrived at the hospital and found a parking space with ease.
We waited until my name was called and then I went into the Chemo room, I was met by very friendly nurses who were excited that I was only the 2nd patient they had had.
Very ground breaking stuff. I sat there while they put the Drug onto the machine and into the vein it flowed.
Phase III trial, expecting to enrol 400 adult patients affected by malignant pleural mesothelioma with disease progressing after a pemetrexed-based chemotherapy. The trial investigates the administration of NGR-hTNF plus best investigator’s choice (BIC) versus placebo plus BIC, where BIC includes either supportive care alone or combined with one chemotherapeutic agent (either doxorubicin, or gemcitabine, or vinorelbine). Randomisation ratio will be 1:1. Before randomisation, investigators decide for each patient if he/she is candidate to either supportive care alone or combined with chemotherapy; patients are then randomly assigned to either of the two treatment arms by specific stratification factors.
NGR-hTNF is given intravenously as 1-hour infusion at 0.8 µg/m2 once a week, until disease progression; placebo follows the same administration schedule in the control arm. BIC is delivered, where applicable and as appropriate, according to Institutional and literature guidelines, and chemotherapy is administered as per standard clinical practice. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, disease control rate, safety, and patient quality of life.
http://www.mesotheliomacenter.org/mesothelioma-news/2010/04/20/molmed-starts-phase-iii-trial-of-ngr-htnf-in-mesothelioma/
The Trial nurse came in to see me and chatted away.
I was given a pack and a DVD with the Navelbine tablets, sickness tablets, steroids all to take when I got home.
Vinorelbine is a chemotherapy drug used to treat breast cancer and non small cell lung cancer. It belongs to the group of drugs called vinca alkaloids. These are often called plant alkaloids because the first of these drugs was developed from the periwinkle plant (vinca) Amazing that a Plant is the answer to cancer. These drugs are sometimes called microtubule inhibitors. This describes the way they work in damaging cancer cells. Vinorelbine works by stopping the cancer cells from separating into two new cells. So it blocks the growth of the cancer.
After and hour of the drug going into me it was over.
I could go home with 2 packs 1 for tonight and then the next Chemo to take next Thursday so they must be stored in the fridge.
We drove home feeling elated that it was so much easier than the first Chemo I had.
After feeding Louis his dinner and having a coffee I had a soup and took my sickness tablet, half an hour later I took the Chemo tablets with a cold juice and that was it.
I feel fine so far just so tired bodily and mentally. I have to have my bloods done at KCC hospital on Tuesday so the results are sent to Maidstone for my Thursday treatment next week.
http://cancerhelp.cancerresearchuk.org/about-cancer/treatment/cancer-drugs/vinorelbine
London St.Barts Trial.
Dr Peter Szlosarek MD, PhD Centre: Molecular Oncology Fellowships: Clinical Research Fellowship (CRUK)Clinician Scientist Fellowship (CRUK)
Job Title: Clinical Senior Lecturer Email: p.w.szlosarek@qmul.ac.uk QMUL Directory Research Interests Dr Peter Szlosarek's main research themes are in Lung Cancer/Mesothelioma, Ovarian Cancer, Senior Researcher and Skin Cancer/Melanoma
Arginine, a semi-essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome. In addition to protein synthesis, arginine is involved in diverse aspects of tumour metabolism, including the synthesis of nitric oxide, polyamines, nucleotides, proline and glutamate. However, several tumours, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer, are unable to produce arginine, due to variable loss of the enzyme argininosuccinate synthetaseASS1 which is necesary for L-arginine synthesisis. Our lab is exploring why ASS1 is aberrantly expressed in human cancers. We have identified methylation-dependent silencing of ASS1 in several tumours, including mesothelioma, ovarian cancer and lymphoma, that are sensitive to arginine deprivation. We are now testing whether the ASS1-deficiency of mesothelioma may be exploited using the arginine-lowering agent, pegylated arginine deiminase (ADI-PEG20). Several phase I/II clinical trials of pegylated arginine deiminase have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1-negative tumours.
Preclinical work in the area of arginine degradation is ongoing in several cancers with our national and international collaborators and industry. We are studying the regulation and modulation of ASS1 expression and the role of the proinflammatory microenvironment in arginine auxotrophic cancers, with the long-term aim of developing novel therapeutic strategies incorporating arginine deprivation and ASS1 loss into routine oncological practice.
We continue to study the links between inflammation and metabolism to discover novel therapeutic targets in oncology.
Profile I graduated in 1994 from King’s College, London with degrees in Pharmacology, Medicine and Surgery, receiving the Pharmacology and Therapeutics Intercalated BSc Prize and Legg Prize in Surgical Pathology.
I obtained the MRCP in 1997, and subsequently trained in medical oncology at St. George's, Guy’s and St. Bartholomew's Hospitals, completing a PhD on the molecular biology of TNF- in ovarian cancer and a postdoctoral position in the Centre for Cancer and Inflammation under Prof Balkwill in 2005.
After a substantive NHS oncology consultant post, I rejoined the BCI as a Principal Investigator in 2008. My translational lab program focuses on aberrant tumour metabolism and inflammation and is closely allied to my clinical interests in the treatment of mesothelial, lung and skin cancers.
***
Maidstone Trial.
Phase 3 NGR-hTNF
30 October 2011 an Update.I was the 2nd to sign up for this trial. But because the patient before me has dropped out I am now the First patient in the Trial and followed by a man who is a week behind me.
This is The Trial That Mavis started on Thursday 13th October 2011This has really been a very interesting day.
We walked Louis and then came home and rung the hospital to let them know we were coming up today so they could make the Trial Drug up, this was what I was asked to do. But, they had no notes on me so I rang the Trial Nurse and she sorted it for me and said would I phone when we are on the M2 this is because the Drug cant sit around.
So I did that as we were on the M2 and arrived at the hospital and found a parking space with ease.
We waited until my name was called and then I went into the Chemo room, I was met by very friendly nurses who were excited that I was only the 2nd patient they had had.
Very ground breaking stuff. I sat there while they put the Drug onto the machine and into the vein it flowed.
Phase III trial, expecting to enrol 400 adult patients affected by malignant pleural mesothelioma with disease progressing after a pemetrexed-based chemotherapy. The trial investigates the administration of NGR-hTNF plus best investigator’s choice (BIC) versus placebo plus BIC, where BIC includes either supportive care alone or combined with one chemotherapeutic agent (either doxorubicin, or gemcitabine, or vinorelbine). Randomisation ratio will be 1:1. Before randomisation, investigators decide for each patient if he/she is candidate to either supportive care alone or combined with chemotherapy; patients are then randomly assigned to either of the two treatment arms by specific stratification factors.
NGR-hTNF is given intravenously as 1-hour infusion at 0.8 µg/m2 once a week, until disease progression; placebo follows the same administration schedule in the control arm. BIC is delivered, where applicable and as appropriate, according to Institutional and literature guidelines, and chemotherapy is administered as per standard clinical practice. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, disease control rate, safety, and patient quality of life.
http://www.mesotheliomacenter.org/mesothelioma-news/2010/04/20/molmed-starts-phase-iii-trial-of-ngr-htnf-in-mesothelioma/
The Trial nurse came in to see me and chatted away.
I was given a pack and a DVD with the Navelbine tablets, sickness tablets, steroids all to take when I got home.
Vinorelbine is a chemotherapy drug used to treat breast cancer and non small cell lung cancer. It belongs to the group of drugs called vinca alkaloids. These are often called plant alkaloids because the first of these drugs was developed from the periwinkle plant (vinca) Amazing that a Plant is the answer to cancer. These drugs are sometimes called microtubule inhibitors. This describes the way they work in damaging cancer cells. Vinorelbine works by stopping the cancer cells from separating into two new cells. So it blocks the growth of the cancer.
After and hour of the drug going into me it was over.
I could go home with 2 packs 1 for tonight and then the next Chemo to take next Thursday so they must be stored in the fridge.
We drove home feeling elated that it was so much easier than the first Chemo I had.
After feeding Louis his dinner and having a coffee I had a soup and took my sickness tablet, half an hour later I took the Chemo tablets with a cold juice and that was it.
I feel fine so far just so tired bodily and mentally. I have to have my bloods done at KCC hospital on Tuesday so the results are sent to Maidstone for my Thursday treatment next week.
http://cancerhelp.cancerresearchuk.org/about-cancer/treatment/cancer-drugs/vinorelbine
