Bill

My wife's pharmacist refilled her Tarceva and stored it in the refrigerator ( in the original, manufacturer's foil sealed container ). Looks like it was in the fridge for ~ 24 hours before I picked it up. Refrigerator temperature would be below the manufacturer's recommended storage temperature range. Because the container is sealed I'm not really concerned about moisture damage but I'm concerned about cold storage stability generally. I can't locate any cold storage stability info on Tarceva ( or Iressa ). The manufacturers don't have any specific knowledge about this subject, either. Just guessing. Actually, there is very little, if any, cold storage data available on any non-refrigerated pharmaceuticals. Studies deal primarily with freezing and high temps. Does anybody have any experience with refrigerated Tarceva ( or Iressa ) ? Thanks.

http://www.massgeneral.org/pubaffairs/i ... 5Haber.htm

IMO it's a mixed message. Sort of a disappointing one as it throws some cold water on the highly toted mutation theory for this group of drugs. But, IMO, what it really means is that you know about as much about these targeted tx drugs as the researchers do. They are rushing these drugs to market with some very preliminary data and very limited understanding and then just winging it. BTW, if you've been following the ASCO meeting you may have picked up on the new spin. Stand alone " targeted " tx is out ... " Multitasking " tx is in. Boy, that was quick ! If this spin sounds familiar it should. It's the same old multi-drug tx approach that we all are very familiar with. What these drug companies and their researchers are already doing is heavily promoting the use of these targeted tx winners in various drug combinations. Of course, Wall Street is pushing this approach full-throttle in order to expand the oncology market and pharmas' bottom line. Let's hope that some real therapeutic benefits can be derived from utilizing these newer targeted tx drugs in a " multitasking " tx setting.

8:21AM OSI Pharm provides clinical data on Tarceva (OSIP) 45.25 :Co provides data of EGFR mutation and gene amplification from the Tarceva registration study in non-small cell lung cancer The survival benefit from Tarceva therapy that was seen for essentially all sub-sets of patients in the BR.21 study was greater, although not significantly, for patients whose tumors expressed EGFR protein and for those patients whose tumors possessed an abnormally high copy number of the EGFR gene. Importantly, the study showed that patients whose tumors had mutations in their EGFR genes experienced no greater survival benefit than patients whose tumors expressed the non-mutated - or "wild-type" - form of the gene.

Mid week my wife began feeling poorly and her low back / hip pain started worsening. Worsening to the point that her Vicodin ES dosage has been upped and she's restarted the OXY IR for breakthrough pain. She saw her PCP on Thursday. He detected some sound percussion " dullness " in the base of her lungs. He ordered a chest x-ray to " check and compare for pleural effusion ". She will be getting this CXR done this morning. She's very despondent over these developments. BTW, my wife's head to toe Tarceva skin rash has now completely disappeared.

Thanks to all for the replies. What startled us most was the sudden disappearance of my wife's severe face rash. The pustular, blistered, bleeding, red flared areas on her face that she consistently had up to a week ago are now gone. As mentioned in my first post, her back still has a rash, actually a mix of clustered red, itchy bumps and patches of dry flaking skin. I'd say that overall her back rash is unchanged or maybe slightly improved. Also, the red spots and dry flaking skin that she had over the rest of her body ( upper arms, torso and legs ) is all gone. Tarceva has certainly proven to be a very erratic acting drug so I recognize that despite this dramatic change that the rash could flare-up again just as suddenly and mysteriously as it disappeared.

FYI over the course of the last few days, and with the sole exception of her back, my wife's head to toe Tarceva skin rash has completely vanished. This includes her severe face rash. This development has taken everybody by surprise, including her med onc and OCNs that saw her yesterday. Obviously, it's very early so there has been no identifiable change in my wife's improved condition as of yet, but given the mounting evidence correlating skin rash with therapeutic effect ( and diminished rash with resistance ) this development is cause for concern. Just more watching, waiting and worrying untl that follow-up PET scan in ~ two months.

My wife has bright red conjunctivitis in both eyes. She has tried a couple of different eye drops ( Visine Original & Murine Tears ) with limited success. No luck completely elliminating the irritation and pain even with the decongestant drops. Usually one eye will continue to bother her even after using these drops. Has anybody found an eye drop or product that completely stops these symptoms ?

My wife has had occasional dry eyes since starting Tarceva. Easily remedied with a drop of two of eye lubricant until recently. More recently her dry eyes symptom has become more of a persistent eye irritation not so easily relieved by eye drops. I have been warned that this eye irritation is a potentially dangerous symptom as it can escalate from conjunctivitis to conditions such as keratitis and corneal ulcers. If one considers the widespread effect that Tarceva has on epidermis from head to toe it shouldn't come as much of a surprise that the eyes may eventually be affected as well. We are in watch and wait mode on this symptom at present. If anybody has seen an ophthalmologist about this problem please share his or her opinion. Thanks.

IMO it could very likely be the radiation. My wife received both WBR and spine radiation at the beginning of her cancer treatment in June ' 04. She tolerated it very well. In fact, so well that it left us with the impression that radiation would be a breeze for her. This past Feb. ' 05 she needed more L-spine radiation. A three week course of tx was ordered. Two days into the radiation she began complaining of unusual weakness, fatigue, SOB, etc. At two weeks these symptoms were extreme and the radiation was stopped. She was hospitalized in the very serious condition that I previously reported. Consensus opinion is that the combination of cummulative chemo effects plus a worsening cancer condition set the stage for the radiation tx to push her over the edge. Best of luck to you.

IMO an MRI of your spine is the way to go. A rad onc or neurosurgeon can readily spot any tumor activity that is present in the spine and then give you an opinion as to whether or not it's related to your pain complaint. As a general rule, spinal tumors don't cause much, if any, pain until they become large enough to compress nerve(s) in the area. Also, as in my wife's case, low back pain can originate from the pelvic region as well as the lower spine.

Public release date: 17-Apr-2005 Measuring enzymes at end of cancer pathway predicts outcome of Tarceva, Taxol ANAHEIM - Researchers at The University of Texas M. D. Anderson Cancer Center have developed a way to test whether the new targeted therapy Tarceva and the widely used chemotherapy drug Taxol are effectively killing tumor cells. They say that with further refinement, the test may make it possible to accurately assess whether patients are responding to these agents, as well as potentially others, within days of beginning therapy. In two different studies being presented at the annual meeting of the American Association for Cancer Research (AACR), the research team will describe how the test measures the activity of several members of the cyclin-dependent kinase (CDK) family of enzymes, which are the triggering molecules that allow a cell to grow and divide. CDK cell cycle enzymes are the end target of numerous cellular pathways that are involved in cancer development and progression, the researchers say. Before these studies, no one has been able to accurately test the function of enzymes from a tumor sample, says Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation. "Testing CDK only has been possible by measuring gene expression, but our industry collaborator has provided a way that lets us test real enzyme activity within a human tumor sample," he says. "Our hope is to be able to use this system as a molecular marker to assess whether an anti-cancer therapy is working." ABSTRACT # 1670 Sensitivity to Tarceva Depends on CDK2 In the first study, M. D. Anderson researchers found that loss of the CDK2 enzyme strongly correlated with a cancer's sensitivity to Tarceva. That means testing activity of CDK2, the enzyme that drives cell division, can reveal whether or not a tumor will respond to Tarceva, says Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation. If results of this study are verified and validated, "a CDK2 test would provide the best marker yet for effective use of Tarceva," he says. The only experimental predictive test currently available is whether lung cancer cells have a mutation in their epidermal growth factor receptor (EGFR), but that does not predict response to the targeted therapy in other forms of cancer, Ueno says. "We find here that as long as CDK2 is suppressed, the drug works, so developing an accurate test for CDK2 activity would be a boon for delivering individualized therapy to patients," he says. Such a test, however, will require that patients be given the drug for a short period of time so that the agent's effect on CDK2 activity can be assessed. In this study, the researchers exposed 10 different human breast cancer cell lines to varied doses of Tarceva and then measured activity of the CDK enzymes. They found that tumor cell death was significantly dependent on whether CDK2 activity was repressed. They then double checked those findings by "putting CDK2 back," Ueno says. "We found that the effects of Tarceva were reduced when CDK2 was given back to the cells, so this shows us that CDK2 is the real target of Tarceva. "This presents a concept that describes how Tarceva works, and it also shows that we have a technology that can rapidly measure the true activity of CDK2 in a tumor sample," Ueno says. First author Fumiyuki Yamasaki, M.D., Ph.D., a post-doctoral fellow, is presenting the findings at AACR. ABSTRACT # 459 Profile CDK to Predict Effectiveness of Taxol A different research team, headed by Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation, found in a second study presented at AACR that if activity of several CDK molecules is increased - not decreased as in the Tarceva finding - then the chemotherapy drug Taxol appears to effectively kill breast cancer cells. Taxol, used to treat a wide spectrum of cancers, works by interrupting the reorganization of the cell that is necessary if it is to divide. While it was known that the primary effect of the drug is to interfere with assembly of the spindle that pulls nuclear chromosomes apart during cell division, Ueno and his colleagues have recently reported that increased activity of CDK1 correlated with a cell's sensitivity to Taxol. The CDK enzyme plays a role in cell division, and researchers believe that it functions in part as a monitor of cell cycle activity. Ueno theorizes that if something goes wrong during division - such as if Taxol is interrupting spindle assembly - CDK will become more active in an attempt to correct the problem. Working with the Sysmex Corporation of Kobe, Japan, the researchers devised a test to measure CDK activity and the expression, simultaneously. They found that monitoring of two isotypes of CDK activity accurately predicted which tumors would respond to Taxol in the experiments with human breast cancer cell lines and tumor tissues of human xenograft model. "This provides solid preclinical evidence that we can use toward development of a novel device that can measure CDK activity in human tissue within several hours," Ueno says. He adds that a clinical trial is currently under way that tests CDK activity both before and after patients with breast cancer are treated with Taxol. ###

http://gumc.georgetown.edu/communicatio ... ectID=4477

FWIW : When my wife was d/c'd from the hospital she was d/c'd with several Rxs including prednisone 40mg. daily. This was ordered by an internist. She saw her med onc two days later. He had a fit when he discovered this Rx and immediately had my wife weened off of prednisone over the next 5 days. He states that corticosteroids are detrimental to her lung cancer condition and should be used only for acute care. He states that long-term use can lead to increased pulmonary congestion in lung cancer patients. I've always been an advocate of corticosteroid use in pulmonary disease, generally speaking, so this precaution was news to me. No details provided by him. I didn't ask as I expected my wife to be weened off of the prednisone anyway.

Karen : I think that the key issue is whether resistance with that particular drug has occurred or not.

I have recently discovered this myself. I noticed that since my wife has been on Tarceva that her radiation window over her L-spine has been particularly noticeable. Actually, just as noticeable, if not moreso, than with the Gemzar.

Fay A. >Posted: Wed Apr 13, 2005 4:40 pm Post subject: Chemo Drug Resistance... I've been told that cancer cells can become resistant to various chemotherapy drugs. Why would an Oncologist prescribe a drug like Taxotere again if the drug was used previously and new tumors grew during the first usage of Taxotere? Aren't those new tumors resistant to Taxoter and other Taxane Drugs? //////////////// FWIW, my wife's med onc just addressed this vary question. In my wife's case it involved switching from Gemzar to Tarceva. He states that once you leave a drug at resistance, switch to another then attempt to return to that previous drug ( as stated above ) don't expect any renewed therapeutic benefit. Expect progression. In fact, his opinion is that once you leave a chemo drug for another there is no going back to that previous drug. I, personally, don't have an opinion about this issue BUT since the question came up here and it is sort of important I am passing this opinion along. Just one man's opinion but probably a worthwhile question to get a second opinion on if you find yourself in such a situation.

http://biz.yahoo.com/ibd/050408/health.html?.v=1 http://www.thestreet.com/_tscana/stocks ... 16725.html

Peggy et al : Here's the problem with my wife's PET / CT results. An interventional radiologist commented that the real ??? is - are those numerous " very small " lung nodules that are under the PET radar inactive ( dead ) residue OR viable tumors simmering and waiting to take off ? Obviously, what is needed is a radiology machine or technique that can both spot very small nodules like the CT can AND identify them as active or not like the PET can. Separately, an x-ray tech that I know scoffed at the notion that 1 -2 mm. lung nodules can be accurately identified on a chest CT ( as has been done in my wife's chest CT report ). She said that in her opinion identifying lung nodules in the 1 -2 mm. range on CT is largely guesswork and the accuracy is very poor. What do you think about that ? Obviously, my wife has improved vs. Jan. ' 05. For that I'm grateful. But, given this significant uncertainty about those numerous very small nodules in BOTH lungs, I can't help but be somewhat disappointed in the results.

For comparison, here's what the 3/28/05 PET reported ( lung portion only ) : FINDINGS : There is a focus of moderately intense hypermetabolic activity in the left upper lobe of the lung. This measures approximately 1.4 cm. and demonstrates standard uptake value of 2.4, borderline for malignancy. This could represent partial response to therapy. ( Note : primary tumor was measured at 2.6 cm. per 1/20/05 CT scan ). There is no evidence of other hypermetabolic foci in the lungs, but they may be too small to visualize. IMPRESSION : Solitary focus in the left upper lobe, probably partially treated malignancy. Here's what the 4/4/05 Chest CT reported : FINDINGS : Spiculated mass, left upper lobe, seen measuring 22 mm., axial image # 15. Very small nodules are seen in the lungs diffusely. These have undergone significant interval diminution in size compared with the CT exam from 1/20/05. No evidence of mediastinal or hilar adenopathy. Thoracic fixation rods and interposition graft are again seen. IMPRESSION : Spiculated mass, left upper lobe, measuring 22 mm. Small nodules seen diffusely throughout the lungs in the 1 - 2 mm. range. Significant interval diminution in size compared with the 1/20/05 exam. No clear-cut mediastinal or hilar adenopathy. No evidence for axillary or supraclavicular adenopathy. No evidence of pericardial effusion.

I've asked a question about this on the Ask The Experts board. If anybody else is familiar with this happening please provide your explanation here. Thank you.

Peggy : IMO 6 days is about right to notice early improvement. My wife had her all-important ( and hopefully PET confirming ) chest CT scan yesterday so results from that should be coming in within a couple of days. I have the CD and I took a peak. I did my amateur comparison vs. her 1/20/05 chest CT and I see what looks to me like a big improvement but beyond that I don't want to speculate and will just have to sweat out the rad report. Good luck and I hope that your husband sees further improvement as the days go by.

Don : The rad onc offered three possible explanations for my wife's PET scan results : 1. ) Tumor eradication to be classified as a ( Tarceva ) Miracle because there's no credible medical explanation for this. 2. ) Malignant tumors are present but are under the radar ( too small , less than 5 ~ 10 mm. ). 3. ) Tumors / nodules are there but are INactive ( someone please translate this for me. What does it mean medically to have inactive tumors ? Dormant with the potential to become active, dead tumor residue or what ? And, shouldn't the presence of ( numerous ) INactive tumors interfer with resp. function as they take up space ? He did say that regardless of the CT scan results it's obvious to him by seeing and examining my wife that she has markedly improved. He said that when he saw her in ICU that she was the sickest that he had ever seen a cancer patient that was still alive. Approx. 80% of her lung cpaacity obliterated with mets scattered throughout her bones. Her ALP almost doubled at the end of Feb. This CT scan should nail this down.