Christine MH-UK
12-22-2007, 11:06 AM
Maybe its because the end of the year is a time for reflection, but I thought about all promising news stories I have read about drugs over the last four years and I wondered what ever happened to them. So I looked the ones that had seemed the most promising up and here is how they have progressed
I put them in order of most advanced/promising first
1. 17AAG (HSP-inhibitor) renamed tanespimycin (also known as KOS-953Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Journal of Clinical Oncology
2007 Dec 1;25(34):5410-7
CONCLUSION: Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2+ breast cancer whose tumors have progressed during treatment with trastuzumab. These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18048823&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum
Current National Cancer Institute trial for local refractory or metastatic breast cancer,but no concurrent herceptin allowed.
2. Celecoxib: lots of work still using the pain reliever combined with different types of cancers and treatments, plus at least one modified version on the drawing board that is more targeted against, but this item seems the most useful
Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation.
Fabi et. al
Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
CONCLUSIONS: The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients
Cancer Chemother Pharmacol
2007 Dec 6
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18071704&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum
3. Taxoprexin (formerly known as DHA-paclitaxel): Had a good phase I trial. It has been tested in lung and esophageal cancers in phase II trials with modest effects
No breast cancer trials listed in clinicaltrials.gov
Given to people but no published results for cancer patients:
4. Dichloroacetate (lactic acidosis and rare metabolic disorders treatment): Trials open for recruitment in Alberta for malignant gliomas, trial for solid tumors not ready to recruit yet. Still, anything that might get at cancer in the brain is to be welcomed
5. Artesunate (malaria drug): May have some anti-cancer properties, particularly when modified, but still at the development stage. Anecdotal reports of use by cancer patients, but nothing more. Still, the National Cancer Institute is investigating its toxicity as part of a malarial trial, so perhaps it is not out of the running. Current research publications on lab experiments, which is a good sign.
Things that have not been given to people, but did extremely well in the rats:
6. 3-bromopyruvate: Got rid of full-blown tumours in lab rats. Seems to still be under analysis to see how it can be best administered, primarily for liver cancer. Certain forms of administration into the liver might cause liver problems according to the rabbit model.
Anyone have anything to add?
I put them in order of most advanced/promising first
1. 17AAG (HSP-inhibitor) renamed tanespimycin (also known as KOS-953Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Journal of Clinical Oncology
2007 Dec 1;25(34):5410-7
CONCLUSION: Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2+ breast cancer whose tumors have progressed during treatment with trastuzumab. These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18048823&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum
Current National Cancer Institute trial for local refractory or metastatic breast cancer,but no concurrent herceptin allowed.
2. Celecoxib: lots of work still using the pain reliever combined with different types of cancers and treatments, plus at least one modified version on the drawing board that is more targeted against, but this item seems the most useful
Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation.
Fabi et. al
Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy
CONCLUSIONS: The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients
Cancer Chemother Pharmacol
2007 Dec 6
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18071704&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum
3. Taxoprexin (formerly known as DHA-paclitaxel): Had a good phase I trial. It has been tested in lung and esophageal cancers in phase II trials with modest effects
No breast cancer trials listed in clinicaltrials.gov
Given to people but no published results for cancer patients:
4. Dichloroacetate (lactic acidosis and rare metabolic disorders treatment): Trials open for recruitment in Alberta for malignant gliomas, trial for solid tumors not ready to recruit yet. Still, anything that might get at cancer in the brain is to be welcomed
5. Artesunate (malaria drug): May have some anti-cancer properties, particularly when modified, but still at the development stage. Anecdotal reports of use by cancer patients, but nothing more. Still, the National Cancer Institute is investigating its toxicity as part of a malarial trial, so perhaps it is not out of the running. Current research publications on lab experiments, which is a good sign.
Things that have not been given to people, but did extremely well in the rats:
6. 3-bromopyruvate: Got rid of full-blown tumours in lab rats. Seems to still be under analysis to see how it can be best administered, primarily for liver cancer. Certain forms of administration into the liver might cause liver problems according to the rabbit model.
Anyone have anything to add?