Bill

How quickly did you start gaining weight once you started Megace ? I'm assuming that any immediate weight gain over the first few days is probably largely due to water retention. FYI my wife started Megace 10cc. ( 2 tsp. ) daily on Monday ( 3/14 ). Please respond ASAP. Her sudden weight gain this week is under scrutiny. I'm trying to determine how much, if any, of this sudden weight gain is due to the Megace vs. other possible causes. THANKS MUCH !

Elaine states " Doctors do not want to be wrong. I don't even think that many of them even consider that they MAY be wrong. The ironic thing is that of all professions, they are the most likely to BE wrong--many, many more times than any other. Think about it. And because medicine isn't all science, Drs are bound to be wrong, I realize that. But the part that gets me is that too many of them act as if they couldn't possibly be wrong--and worse they act like the patient is pretty much always wrong--. Of all the things that have happened to me, I have yet to hear a Dr. admit wrong or to even say "I'm sorry." Even to the point that when it is obcious that someone WAS wrong, current Doctors will always make an excuse for previous Doctors. Oh, it really burns me! TAnnstates : Elaine is right, doctors DO NOT like to admit when they are wrong ... Let this be a lesson to those doctors. I promise you, they have taken note of it, even if they aren't admitting anything "out loud". ////////////////////////// This is a very serious issue. IMO it's not at all farfetched to state that there are people out there, including physicians sworn to heal the patient, that will see the patient suffer or worse IF that's what it takes to save face, be right or at least not admit to being wrong. The squirming and spinning and convoluted explanations that I've witnessed from a couple of these people is pathetic. And, much of the covering and related explanations make absolutely no sense. It's whatever you can grasp from thin air that appears to help support a loosing position. No continuity, no relevance, just whatever works to save face. As I previously reported, my wife's X-PCP was visibly irritated when he showed up in ICU and the nurse reported to him that the ventilator that he said would never be removed had been successsfully removed. And, how bout that Gemzar. Maybe great for others but absolutely worthless for my wife yet to this day her med onc continues to claim that Gemzar hasn't failed despite a mountain of dx tests and scans clearly showing a downward spiral in her condition leading up to this current life threatening respiratory crisis in ICU !

As recently as my wife's 3/4/05 chest x-ray her lungs appeared obliterated. Mottled white ( " diffuse infiltrate " ) lung fields with numerous small superimposed white spots ( nodules ) of various sizes scattered throughout both lungs. Plus the primary tumor in the upper left lung. In my estimation 80% of her lung fields were obliterated white. She was admitted to ICU in resp. failure, CHF and compromised renal function. As of yesterday's chest x-ray, a majority of this damage has disappeared. Yes, the problems that I speak of are associated with attitude that surfaced in the ICU. The low point for my wife was when she surprised everyone by successfully being weened off of the ventilator only to be told by a visibly irritated PCP ( the one that we subsequently fired ) that it didn't matter as she would continue to get sicker and die anyway. ( He's the one that announced the day before that my wife would never be able to be weened off of the ventilator and therefore never regain consciousness ). Family and friends have a theory about her med onc's strange attitude towards Tarceva. Bottom line is that he didn't really make the decision to RX Tarceva. He was pressured big time by me, my family and at the end a whole host of healthcare professionals. He can hardly take credit for RXing Tarceva and any good outcome under such conditions. This would explain why he refuses to admit that Gemzar ( his choice ) failed and that Tarceva may be a smart move and in fact work. Others suspect that even if Tarceva undeniably works that the med onc will continue to poo-poo the results UNTIL he can find a window of opportunity to step in and claim that he made the call. He has already taken a small step in this regard by going from being opposed to RXing Tarceva to stating that RXing Tarceva has merit but was done too early. ( Too early ? HeII, my wife ended up in the ICU on a ventilator with resp., cardiac and renal failure and was expected to live only a few more days ! ) It was suggested to me that this med onc may find it easier to eventually take charge of, and get credit for, this Tarceva move if I stay clear of him. I will gladly obliged if it will help. I don't want to damage his ego any further.

What the heck is that all about? How the heck would he/she know or even comment about her metastatic condition when they were only looking at a lung scan report. (I assume the report was for a lung ct since you mentioned lung nodules, although I guess you didn't state that specifically) Anyway, I guess I'm convinced the Tarceva is helping her, but that might be because that's what I want to believe. Sometimes if you believe something enough, it comes true. All my best! Love, Peggy Your question is precisely what I questioned. First, every rad report preceeding yesterday's had talked about lung nodules ad nauseum. Suddenly, yesterday's rad report makes no mention of lung nodules. And, why did the radiologist feel it necessary to add that RE: my wife's marked lung improvement : " it is relatively unlikely this represents improved metastatic disease " ? Another stretch that you didn't comment on. My wife's med onc was quick to opine that her improved lung condition was largely due to tx of a pneumonia ( with Levaquin ). Problem with that opinion is that the hospital's overwhelming opinion is that my wife's pleural effusion and resp. failure was " malignant ' in origin not pneumonia. The Levaquin was given as a prophylactic measure only. So, what's the deal here ? As I keep stating, why are these medical people trying so hard to pick apart this recovery ? BTW, re: the L-spine radiation and hip pain, even the rad onc doubted that L-spine radiation alone would end the pain. He expected that the pelvic cancer was equally the cause. Her neurosurgeon says that the pelvis is the entire cause of the hip pain, not the L-spine.

An update as promised for you Tarceva / Iressa followers : Mild scattered rash on chest and back. Skin on back also looks dry. Basically unchanged for the last several days. Face, esp. nose, cheeks and chin reddish and dry looking. This is a newer development. Overall rash issue is manageable with skin creams so far. A few bouts of diarrhea but not frequent and manageable so far with Lomotil and some pain meds. My wife's mobility has greatly improved. Walking, bending, sitting up, assuming various positions, etc. Hip pain is now minimal. She states that her breathing is normal. She appears to be breathing w/o any discomfort. Overall she feels good but still a bit weak and gets fatigued easily ( Tarceva ? ). Her PCP just RX'd Megace susp. Her appetite is already fairly good so we hope that she can now put on a few of those recently lost pounds. Here is the hard part in reporting progress to you. At least progress as it pertains to Tarceva. Her med onc, one radiologist and some of the others monitoring her condition refuse to give Tarceva any credit at this stage. I think that we have a few bruised egos in the medical crowd which is part of the problem. A little woman and her drug making fools of doom and gloom medical prognosticators that have written her off. I honestly don't know if Tarceva has helped to this point and, if so., how much. I wish I knew and as stated before I am open to any input on how to help sort this out. Today is day 13 on Tarceva. My wife had a chest x-ray yesterday. " Marked improvement " over previous hospital chest x-rays ( 3/3 & 3/4 ). But, as I just stated, no credit goes to Tarceva. My wife was in the midst of L-spine radiation when this latest medical crisis unfolded. Her med onc says that her suddenly diminished hip pain is probably due to that radiation, not the Tarceva. Yesterday's radiology report doesn't mention any lung nodules but concludes that marked improvement noted is " relatively unlikely " to be indicative of an improvement in her metastatic condition. My wife's med onc also says that the lung improvement is largely do to tx for a pneumonia but the hospital pulmonologist and the cytology report on the pleural fluid say the cause is likely malignancy. Go figure. So, as I laid out in my other post today, here we are up against the medical establishment that considered my wife's condition to be a lost cause and they seem equally unconvinced about Tarceva's effectiveness. They seem eager to poke holes in her improvement and are ready to say ' I told you so '. I have the chest x-rays with me. The lungs fields are significantly clearer on yesterday's chest x-ray ( as opposed to 3/3 & 3/4 ). I do see a larger spot in the upper left lung which would be the primary tumor and I do see 2 or 3 small spots elsewhere in the lungs which are probably nodules. But, other than a small amount of whitish " infiltrate " that's about it.

IMO, and I'm only speaking from my personal experience, the medical establishment mentality towards the terminally ill ( in my wife's case Stage 4 NSCLC with brain, bone and some soft tissue mets ) absolutely STINKS. IMO it's largely a statistical mentality and any attempt to derail this expected grim statistical outcome is met with resistance. It runs the gamut from cold hearted clinicians that openly write off the patient to compassionate clinicians that don't see much hope but at least are willing to cooperate with continued tx efforts. We are fortunate that my wife has a new PCP and another specialist or two that fit the latter category. Unfortunately, the majority fit the former category. I have run into very formidable resistance in getting some of these clinicians to cooperate with any further tx efforts. For instance, even my wife's med onc had to be pressured by several colleagues into prescribing Tarceva. I mean he was hammered by at least 10 physicians, nurses and social workers over the course of a single day leading up to him RXing Tarceva that same evening. My wife's previous PCP stoned walled tx efforts and painted such a horrible picture to my wife and the family that he was fired right in ICU and replaced by a compassionate PCP that was willing to let my wife live to fight another day. Also, a hospital case manager that overheard this PCP's very harsh and cruel comments reported him to his supervisor. I intend on reporting him to the CMA. Even the radiology reports from chest x-rays and scans related to my wife's latest crisis and hospitalization contain unnecessary verbage inserted as if to rule out any improvement noted as indicative that her metastatic disease may be improving. I even had one physician question my wife's resuscitation orders ! Also, FYI, I am surprised at how few clinicians are familiar with Tarceva and Iressa beyond the names. Most have no idea at all about how these drugs work when they WORK and the role that they might play in a case such as my wife's if they work. Yet, these same people are the ones making judgment calls about her condition and destiny. The battle to keep this resistance in check has become bigger than the cancer battle itself. It is extremely draining and definitely unappreciated. At this writing I honestly don't know how much Tarceva has contributed to my wife's marked improvement. Still too soon I guess and time will tell. But, this I do know. Had it not been for a couple of compassionate clinicians, she wouldn't have even been given the opportunity to find out.

CD : Thanks. Makes sense. Barring successful chemo tx to stop it or significantly slow it I'd expect malignant pleural effusions to keep recurring. I would sure like to know how rapidly they typically recur in the absence of successful chemo tx. My wife's last chest x-ray ( that I saw ) showed a slight reaccumulation of fluid in the base of one lung. This would have been 2 days after draining and the day before she started Tarceva.

A question for those of you that have had a pleural effusion drained that was determined to be cancer-induced ( vs. infection induced ). Based on your personal experience with this, or any input received from your treating physicians, what is the approximate / typical timeframe for reoccurence ? This assumes no interventional tx after draining the pleural effusion other than a short course of meds ( e.g. Lasix, steroids, etc. ). TIA for any input on this subject.

Can you share any details re: your continued need for prednisone / decadron ? I understand their role in lung cancer but considered these drugs to play more of a minor, supportive and temporary role in controlling secondary inflammation. In your case I get the impression that these steroids are playing a major role. Almost as if the steroid is the frontline drug in your case. I am also interested in this subject because my wife is currently being weened off of very high dose prednisone. I'm nervous about her ability to sustain her respiratory improvement as the prednisone is d/c'd. Thanks much for any comments that you can share and good luck to you.

Just wanted to contribute a couple of interesting side notes re: Tarceva availability and dosing. It looks like obtaining Tarceva on an out-patient basis is easy and the only issue for some may be getting medical insurance reimbursement. I found securing Tarceva for my wife on an outpatient basis to be routine with prior authorization being the only insurance requirement. BUT, listen to this : My wife was prescribed Tarceva ( by her med onc ) WHILE SHE WAS IN THE HOSPITAL. A large SO CA medical center. Iressa is on the med ctr drug formulary BUT Tarceva isn't. They still consider Tarceva an investigational drug and as such the drug cannot be prescribed or administered to a hospital patient w/o first going thru an approval process that includes committee review. In my wife's case the Tarceva was made available to her immediately on an emergency basis but only after invoking Heath & Safety Code 11167. Also, of interest her med onc prescribed 200mg. and the hospital approved 150mg. which the med onc agreed to and has maintained.

Thanks for the replies. It's Day # 9 of Tarceva and my wife's adverse effects profile with Tarceva is still unclear. As of this writing the skin rash, which popped up a couple of days ago, is mild and is isolated to her chest and back. Scattered / pink / raised / itchy small spots but really no problem for her. The problem right now is the GI distress, namely cramping, nausea and diarrhea. IMO the diarrhea is being worsened because she is also in the process of having her daily narcotic load reduced. This is proving to be a complex process as she is coming off of a very high dosage level of I/R and L/R oxycontin. Also, she is being weened off of prednisone. BTW, she reports that her respiratory functions feel " normal ". No visible signs of respiratory distress that I can see. Also, she states that her hip pain has lessened and the sciatic pain in her left leg is gone. One last thing. We all know that " traditional ' chemotherapy can be brutal on blood values. But, I have heard or read nothing re: the impact of Tarceva or Iressa on blood values. Does anybody have any info on this ? Thanks again.

I would be interested in hearing about how soon after starting your Tarceva and / or Iressa did adverse effects appear ( presumably skin rash and / or diarrhea ), severity of those symptoms and how those symptoms played out over time ? Lastly, are you aware of any evidence correlating side effects with therapeutic effect ? Thanks much for any input on this subject.

TAnn and others : You nailed it. It's my nature to be cautious and even skeptical about improvement. I'm in a " show-me " mindset with Tarceva right now. I'm appreciative of any improvement in my wife's condition BUT I anxiously wait for continued improvement that can be more clearly attributed to Tarceva. I honestly can't determine how much of this early improvement is hospital heroics ( e.g. pleural effusion drained, resp. tx, emergency meds. etc. ) vs. Tarceva. I'm open to opinions on this. This is why I've tried to provide an accurate description of her condition with a timeframe for reference. Thanks again to all.

My wife's breathing is " normal " this morning with no apparent signs of respiratory distress. She's breathing room air only. No supplemental oxygen. Her hip pain appears to have lessened but it's difficult to quantify this improvement right now as her current narcotic pain med regimen is excessive and is being kept largely unchanged in order to stave off withdrawal. She will be seeing her med onc this afternoon and hopefully she can start gradually reducing the pain med regimen so that it more closely approximates her actual pain relief needs. She is ambulatory without assistance. She has a mild skin rash as reported yesterday. She has diarrhea which is probably largely due to the Tarceva. It looks like the plan is to maintain the Corgard and pepcid, ween off the prednisone 40mg. and prn the lomotil, Xanax and Restoril. She is still weak and needs nutrition and some weight gain.Thanks again for the kind words and helpful input.

Yesterday ( Day # 5 of Tarceva 150mg. ) I visited my wife and I noticed some scattered small / red / raised spots on her back. I haven't seen her yet this morning but a nurse reported to me that she now has these spots on her legs ( thighs ) and neck area. Sounds like the Tarceva skin rash. What I would like to know from you veteran Tarceva / Iressa rash suffers is what product(s) have you found to be the best at treating this condition ? Thanks much.

I have a question re: the ability of these drugs to delay progression of the disease. IMO the initial improvement that one may see with Tarceva or Iressa is great. It helps defuse any imminent medical threat and it stablizes the condition. BUT, what I want to hear from any and all Tarceva and Iressa responders is input as to how long your disease has been held stable, with no evidence ( scans, etc. ) of progression. Thanks much.

Day # 4 of Tarceva 150mg. today. It's VERY early and there's along way to go before I'll be convinced that the Tarceva is responsible for this improvement. But, this afternoon my wife is walking the full length of two hallways ( with a walker ) while talking. Her appetite is good which is good since she lost 5 pounds this week ( 120 ~ 115 ). Six days ago she was intubated in ICU and the docs told my family that she was near death and to say our goodbyes NOW or never. Following removal of the ventilator the next day she was so ill that she could barely breath and talk let alone sit up or walk. My wife's medical condition closely approximates the Iressa case that Dr. Joe sited in his 9/15/04 post. Massive pleural effusions ( with dark cola colored fluid ~ bloody exudate ) left lung collapsed with secondary CHF and renal insufficiency and mets throughout the body including new mets in her ribs, scapula and I think fubulas. Wide spread and severe bone pain. Her ALP level doubled in a week. Providing these updates, whether it be good or bad news, will be my way of giving back to this LC board. IMO this represents a deathbed scenario that will truly put Tarceva to the test. I think that this battle, whichever way it ends, will be beneficial to others facing a similar situation. Thanks again for the kind words and support.

First, I want to sincerely thank everyone for the kind words and support in response to Fay's post about my wife. Her health condition has significantly deteriorated over the past week. Her condition is stable at this writing but stable at a much lower level than a week ago. She started Tarceva 150mg. on Thursday ( 3/3 ). Consensus opinion amongst her healthcare providers is that barring a miracle recovery with Tarceva she has only a few weeks to live at most and that hospice is in order. A hospital clinical case manager mentioned to me that she thought that my wife could enter a hospice program and continue taking Tarceva without violating hospice no-treatment policy. She based this on Tarceva being an ORAL medication. Is this true ? Also, can anybody give a brief description of what a typical at-home hospice program would provide. I assume that pain meds and such would still have to come from the med onc and other treating physicians ? Thanks again.

Study identifies mechanism of resistance to targeted therapy in lung cancer patients Findings help explain how cancer cells develop resistance to gefitinib A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) identifies a second mutation in a gene associated with non-small-cell lung cancer (NSCLC), a discovery that helps to explain why NSCLC tumors become resistant to treatment with the cancer therapy gefitinib (Iressa). The findings, which are reported in the February 24, 2005 issue of The New England Journal of Medicine (NEJM), could help lead to the development of second-generation inhibitor drugs to treat NSCLC, which accounts for approximately 85 percent of all lung cancer cases and is the leading cause of death from cancer in the U.S. among both men and women. One of a new generation of cancer therapies that work by disrupting the specific molecular target responsible for stimulating tumor growth, gefitinib acts on the receptor for the epidermal growth factor protein (EGFR) to halt the spread of cancer cells. In 2003, it was approved by the U.S. Food and Drug Administration as a treatment for NSCLC. Clinical applications of the new drug initially yielded very good results, with approximately 10 percent of patients experiencing complete remission of their disease. Two separate studies published last year in NEJM and Science offered an explanation for how this was happening, suggesting that a mutation in the EGFR gene of these individuals was causing their cancer cells to produce abnormal versions of growth signals called tyrosine kinases. Among these patients, gefitinib works by snugly fitting into the activating pocket of the protein like a key into a keyhole, blocking the growth signals and thereby depriving the cancer cells of the stimuli they need to survive and proliferate. However, in spite of the therapy's initial success, patients inevitably suffered a relapse and their tumors started to grow again. "It appeared that the tumors in these patients had found a way to bypass the effects of gefitinib," explains the study's last author Balazs Halmos, MD, a physician-scientist formerly at BIDMC and presently with the Ireland Cancer Center, University Hospitals of Cleveland. To detemine if this was indeed the case, Halmos identified a 71-year-old patient with advanced NSCLC whom he had been treating at BIDMC, and who had recently relapsed after two years of complete remission while undergoing gefitinib therapy. Hypothesizing that the relapse may have been due to another mutation in the EGFR gene which was causing cancer cells to become resistant to the drug, Halmos, together with the study's corresponding author Daniel Tenen, MD, a molecular biologist in the Division of Hematology/Oncology at BIDMC, and Susumu Kobayashi, MD, PhD, a physician-scientist in Tenen's laboratory, obtained a second biopsy of the tumor and resequenced the EGFR tyrosine kinase domain. Their studies confirmed the existence of a second mutation, and insertion of this mutation into test cells rendered them resistant to gefitinib in vitro. Further analysis revealed that the newly identified mutation was altering gefitinib's drug-binding pocket and thereby changing the "keyhole" so that the "key" – gefitinib – no longer fit. "The development of a second mutation suggests that the tumor cells remain dependent on an active EGFR pathway for their proliferation," explains Tenen, who is also a Professor of Medicine at Harvard Medical School. "This mirrors the situation that developed over the past few years among patients with chronic myeloid leukemia and gastrointestinal stromal tumors who were being treated with imatinib [Gleevec]." In those cases, he adds, the identification of mechanisms of resistance helped lead to the development of second-generation inhibitor drugs now being clinically tested. And in fact, according to study coauthor Bruce Johnson, MD, Director of the Dana-Farber/Harvard Cancer Center Lung Program, clinical investigators are already moving in this direction. "Our preliminary results have yielded encouraging findings, pointing towards drugs that might bypass this method of resistance," says Johnson. "We're now in the process of planning clinical studies to test novel EGFR inhibitor compounds in lung-cancer patients whose tumors have become resistant to gefitinib." The results may also lead to new diagnostic methods. "I believe that findings like these will hasten the use of molecular oncology for everyday practice," says Tenen. "Analogous to the way that antibiotic and antiviral regimens might be selected today based on the results of microbiological testing, I can certainly envision a time in the future when molecular monitoring for mutations and drug regimens will be adjusted based on these results." In addition to Halmos, Tenen, Kobayashi and Johnson, study coauthors include BIDMC investigators Olivier Kocher, MD, PhD, and Tajhal Dayaram, BA; and Dana-Farber Cancer Institute investigators Titus Boggon, PhD, Michael Eck, MD, PhD, Pasi Janne, MD, PhD, and Matthew Meyerson, MD, PhD. ### This study was funded by grants from the National Institutes of Health and the Dana-Farber/Harvard Cancer Center Lung Cancer SPORE Program. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Care Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.harvard.edu.

This is a very difficult issue because it cuts both ways. In my wife's case, closely monitoring symptoms and at times scrutinizing and obsessing over her symptoms has paid off with some helpful tx but it has also backfired. In a couple of instances she received unnecessary and possibly detrimental tx ( including delayed tx ) because I insisted on action due to a couple of ' symptom headfakes '. I gotta go. Monitoring the wife's occasional chest pains ( sternum ) and extreme fatigue. Hopefully, just residual effects from Wednesday's P-A-C implant and Gemzar / Navelbine.

Thank to all for the additional replies, including the K&D compliment. I do try to detail my posts so that not only are my personal needs met but that other readers can possibly extract some useful info as well. This thread has taught me alot about the PAC. As a result, come Wed. morning I will be that much more aware when the procedure actually takes place. My wife gets the PAC implanted at the hospital then goes directly to the med onc for a chemo session. Then, back to the hospital if necessary. BTW, I will double check this on Wed. but I spoke briefly to the OCN by phone this afternoon and she stated that my wife's med onc doesn't prescribe a daily anticoagulant ( such as coumadin ) for PAC patients.

I was over at the hospital this morning so I dropped by radiology and asked a nurse about this. She stated that the ultimate catheter destination for the PICC line and Port-A-Cath is the same. She speculated that the Port-A-Cath insertion MAY have a better outcome because of the insertion location. But, only a guess on her part and she said to tell the interventional radiologist about the PICC difficulties. I sure hope that this procedure is a success. My wife's condition is fragile and she really can't tolerate any more complications.

One lingering thought that troubles me. When my wife was in ICU they made four failed attempts to insert a PICC line. The catheter kept turning up instead of down at the major vessel bifurcation. They finally gave up. Does anybody know if this is the same major vessel bifurcation that is used for the Port-A-Cath ? If it is, I have to hope that the insertion location used for the PAC implant allows for a better approach and result.

Please clarify when you take an anticoagulant. Is it routinely given as part of having a Port-A-Cath, or is it given during chemo breaks only or is whether or not it's given at all determined case by case based on the patient's medical history ? Thanks.