Recycling chemo drugs

Hi,
I have probably exhausted all the chemo regimens possible. In the last 5 yrs I have had AC,taxol, navelbine,Xeloda, Gemzaar and Cisplatin in combo with herceptin. Each chemo worked for sometime and I had to move on. I stopped Gemzaar and cisplatin because of toxicity. I have never been in remisssion, Is there any other chemo drug for me? Has anybody recycled and of the chemos already used and what was the response? I am thinking on the lines of Navelbine as the side effects werem tolerable and this drug lasted the long. I have also taken arimidex and femara and this does not seem to be working either. Any response from you would be appreciated.
Hugs,
Ragini

[Lyn]

HI there, yep there are still chemo drugs left, Abraxane is one and in the taxane family but not as harmful and apparently better than Taxol or Taxotere. Most chemos can be used again after a break of about 12 months. Lolly always seem to go back to Navelbine and it works for her. I was on Aromasin (femara did nothing for me) for a while and enlarged glands disappeared and I didn't need radiation, but like you I never seem to into remission and I have been doing this since 1998, lymph glands and skin, now other breast, what are you treating this time?

Love & Hugs Lyn

[Lolly]

Hi Ragini; As Lyn says, Abraxane has shown some good results, and some docs are combining Avastin, one of the new anti-angiogenisis drugs, with chemo/Herceptin combos.
I have been lucky to be able to go back to Navelbine for each of my recurrences; I just started it last month for the third time since 2001. My onc says the key is if a drug has provided a good response and if it's been over a year since the last use of that drug it may be effective again. Apparently the cells can "forget" the previous expousure. It's definitely worth exploring with your onc.
<3 Lolly

[lu ann]

My doc took me off taxol, and carboplatin last November after 6 months of tx. Although my ca15-3 counts were down to 21, he thought I was progressing because I had pleural effusion.

I was put on Navlebine in Dec. 04 and counts climbed to 37.

We switched to gemsar in Feb. 05 and my last counts were 117 Oct. 05. My current doc wants to keep me on gemsar because my pleural effusion has lessened and bone mets are stable.

I've been on monthly zometa since Feb. 04 and herceptin since May 04, with the exception of a 3 month break from herceptin May-Aug. 05.

The first 2 months of the tax., carb., herc., and zom. tx. were rough, mostly achey flu-like symptoms. Mr tx. were 3 weeks on/1off. I never had neuropathy. My hair thinned and started to grow back after the 4th round. I'm thinking that maybe I could go back on the taxol, carbo., her., zom., combo if I run out of options.

This whole game is like a crapp shoot. I never did like to gamble.

Love and Blessings, Lu Ann.

Perhaps you could try Fulvestrant. It works via a totally different mechanism of action than tamoxifen or raloxifene (which block the estrogen receptor) or the AIs which block an enzyme which converts precursors to estrogen in post-menopausal women in an effort to "starve" the estrogen receptor of its ligand.
Unfortunately breast cancer cells have their OWN estrogen factory which uses one of THREE different enzymes to make estrogen and AIs only block one of these.

Fulvestrant binds to the estrogen receptor and then degrades it PERMANENTLY.

Unfortunately it does this not only on breast cancer cells, but on all cells containing estrogen receptors. Not a big problem for someone like you who has withstood multiple chemotherapy regimens.

I have posted in other threads at least four articles on the use of fulvestrant and will again if you let me know that you can't find them.

In addition, unless you have lost a lot of weight, it might be interesting to try Xenical, a weight loss medication made by Roche (who market Herceptin in Europe).

I don't think it could hurt unless you forgot to take your fat soluble vitamins (Vitamins A,D,E, and K) several hours before or after you took your Xenical
or if you got very dehydrated by diarrhea, which I am quite sure you could look out for and avoid. Also you would have to remember to take your flaxseed oil, evening primrose oil, and/or olive oil simultaneously ( with similar timing as that described above)

The article, based on in vitro experiments (in the lab, not in live humans) has shown strong synergy with Herceptin.

I am posting the reference:
: Menendez JA, Vellon L, Lupu R. Related Articles, Links
Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene.
Ann Oncol. 2005 Aug;16(8):1253-67. Epub 2005 May 3.
PMID: 15870086 [PubMed - in process]

I will post the abstract in my next post--I am always losing my efforts when attempting to switch between programs and cut and paste--

What could be better than fighting your breast cancer and becoming "svelt"
in one fell swoop! ( I hope the chemo has not left you overly thin preventing you from trying this option). This may be an unorthodox option, but if it might work....!

Hope these ideas help!

LANI

1: Ann Oncol. 2005 Aug;16(8):1253-67. Epub 2005 May 3. Related Articles, Links

Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene.

Menendez JA, Vellon L, Lupu R.

Department of Medicine, Breast Cancer Translational Research Program, Evanston Northwestern Healthcare Research Institute, Evanston, IL, USA. jmenendez@enh.org

BACKGROUND: Orlistat (Xenicaltrade mark), a US Food and Drug Administration (FDA)-approved drug for bodyweight loss, has recently been demonstrated to exhibit antitumor properties towards prostate cancer cells by virtue of its ability to block the lipogenic activity of fatty acid synthase (FAS). FAS (oncogenic antigen-519) is up-regulated in about 50% of breast cancers, is an indicator of poor prognosis, and has recently been functionally associated with the Her2/neu (erbB-2) oncogene. MATERIALS AND METHODS: We assessed the antitumoral effects of orlistat against the human breast cancer cell line SK-Br3, an in vitro paradigm of FAS and Her2/neu overexpression in breast cancer. RESULTS: Cell cycle analyses revealed that micromolar concentrations of orlistat induced, in a time- and dose-dependent manner, significant changes in the distribution of cell populations including a complete loss of G2-M phase, S-phase accumulation and a concomitant increase in the emerging sub-G1 (apoptotic) cells. Poly (ADP-ribose) polymerase (PARP) cleavage, an early event required for cells committed to apoptosis, was more predominant in orlistat-treated G1 phase cells. When we characterized signaling molecules participating in the cellular events following orlistat-induced inhibition of FAS activity and preceded inhibition of breast cancer cell proliferation, a dramatic down-regulation of Her2/neu-coded p185(Her2/neu) oncoprotein was found in orlistat-treated SK-Br3 cells (>90% reduction). Interestingly, a significant accumulation of the DNA-binding protein PEA3, a member of the Ets transcription factor family that specifically targets a PEA3-binding motif present on the Her2/neu gene promoter and down-regulates its activity, was observed in orlistat-treated SK-Br3 cells. When a Luciferase reporter gene driven by the Her2/neu promoter was transiently transfected in SK-Br3 cells, orlistat exposure was found to dramatically repress the promoter activity of Her2/neu gene, whereas a Her2/neu promoter bearing a mutated binding DNA sequence was not subject to negative regulation by orlistat, thus demonstrating that the intact PEA3 binding site on the Her2/neu promoter is required for the orlistat-induced transcriptional repression of Her2/neu overexpression. RNA interference (RNAi)-mediated silencing of FAS gene expression similarly repressed Her2/neu gene expression in a PEA3-dependent manner, thus ruling out a role for non-FAS orlistat-mediated effects. When the combination of orlistat and the anti-Her2/neu antibody trastuzumab (Herceptintrade mark) in either concurrent (orlistat + trastuzumab) or sequential (orlistat --> trastuzumab; trastuzumab --> orlistat) schedules was tested for synergism, addition or antagonism using the combination index (CI) method of Chou-Talalay, co-exposure of orlistat and trastuzumab demonstrated strong synergistic effects (CI10-90 = 0.110-0.847), whereas sequential exposure to orlistat followed by trastuzumab (CI10-90 = 0.380-1.210) and trastuzumab followed by orlistat (CI10-90 = 0.605-1.278) mainly showed additive or antagonistic interactions. Indeed, orlistat-induced FAS inhibition synergistically promoted apoptotic cell death when concurrently combined with trastuzumab as determined by an ELISA for histone-associated DNA fragments. Importantly, the degree of FAS expression in a panel of human breast cancer cell lines was predictive of sensitivity to orlistat-induced anti-proliferative effects as determined by a MTT-based characterization of metabolically viable breast cancer cells. Moreover, hypersensitivity to orlistat-induced cytotoxicity was observed in MCF-7 breast cancer cells engineered to overexpress Her2/neu (MCF-7/Her2-18 cells), which exhibit a significant up-regulation of FAS expression and activity. CONCLUSIONS: These findings reveal that the development of more potent and/or bioavailable orlistat's variants targeting the lipogenic activity of FAS may open a novel therapeutic avenue for treating Her2/neu-overexpressing breast carcinomas.

PMID: 15870086

Another new monoclonal antibody, bevacizumab has recently completed Phase III clinical trials for the treatment of locally advanced or metastatic breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) and acts to inhibit tumour angiogenesis (process of diverting nutrients to the tumour).

The randomised Phase III trial was coordinated by the Eastern Cooperative Oncology Group to compare the efficacy and safety of paclitaxel with or without bevacizumab as first line therapy in patients with locally advanced or metastatic breast cancer. 722 patients were recruited between December 2001 and May 2004 and were divided into two groups receiving either paclitaxel alone or the combination of paclitaxel and bevacizumab. The primary endpoint was progression-free survival (PFS).

The results were positive and indicated that the combination of paclitaxel and bevacizumab improved overall survival of patients than receiving paclitaxel alone (no final data available yet). Importantly the progression-free survival was improved with combination therapy, 10.97 months vs 6.11 months for paclitaxel alone. In addition, the investigators noted that combination therapy did not cause significant toxicity effects.

Speaking at ECCO 13, Dr Kathy Miller from the Indiana University Cancer Centre, USA, commented, "This is the first study to confirm the benefit of anti-angiogenic therapy in patients with breast cancer. Importantly, the improvements in response rate and progression-free survival were obtained with minimal increase in side effects. Given the benefit of bevacizumab in patients with metastatic disease, we look forward to initiating trials in the adjuvant setting."

http://www.toniclc.com
The above trial was for first-line therapy of MBC--you certainly do not fit that prescription.
I think Mark Pegram of UCLA is running a trial of Herceptin and Avastin. I am not
certain of the requirements to enter his trial, but there is a link on this website to UCLA clinical trials.

There may also be a trial of Ipimipazab ( will get the real name and add it to the post later) at the NIH and other sites, I believe. Again, I do not know the entry requirements.

Where are you located? How hormone positive was your tumor (not just the percentage positive, but a quantitative measurement of how MANY hormone receptors you have on your breast cancer cells)?

Lots of food for thought!

Good luck,
Lani