End of the year drug pipeline review

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/en...ubmed_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/en...ubmed_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?

alw · 12-22-2007, 08:40 PM

Phase II: RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Metastases

RTA 744 is a novel, anthracycline that has shown the ability to circumvent ATP-binding cassette transporters (Multidrug Resistance Protein 1, Breast Cancer Resistance Protein, P-glycoprotein) in vitro. This action enables RTA 744 to penetrate across the blood brain barrier. In a Phase I safety study, RTA 744 was shown to be generally well tolerated in patients with recurrent gliolastoma multiforme (GBM). Additionally, anti-tumor activity was observed. Breast cancer is known to be sensitive to anthracycline therapy. Based on the preliminary Phase I clinical results and the sensitivity of breast cancer to anthracycline therapy, this Phase II study will investigate the safety and efficacy of RTA 744 in patients with breast cancer and metastatic disease to the brain which has progressed following whole brain irradiation.

http://www.reatapharma.com/rta744.asp

runtolive · 12-24-2007, 07:23 AM

trastuzumab-dm1 from genentech.. its herceptin ..linked to a maytansine toxin.. its currently in a phase 2 trial being dosed at 3.6mg/kg..

at the SABC..san antonio breast cancer symposium.. genentech reported results on their phase 1 patients..

5 of 15 patients with MBC...metastatic breast cancer had a partial response.. and 7 of the remaining 10 pts.. had stable disease...

so 12 of 15 pts are no longer in danger of dying this year because of genentech... the trials are being run at over 30 sites nationwide.. so for women who have been on herceptin in the past and relapse..
THERE IS HOPE...

they are also running a second phase 1 escalation trial to see if weekly dosing is better than every 3 weeks.. some ladies on this board are in both studies and by all accounts.. are doing FANTASTIC...