The National Coalition for Cancer Survivorship (NCCS) is the oldest survivor-led advocacy group, and they recently released some highlights of their study on perceptions of chemotherapy vs. the experience of patients who actually underwent chemotherapy for a cancer in the last few years.  Because several membes have raised questions of whether the treatment is likely to be worse than the disease, I thought the results of this study would be of interest here and that members might want to add their own impressions. 

   The study was sponsored by Harris Interactive and sponsored by NCCS along with the large pharmaceutical company sanofi-aventis.  In November of 2007, they questioned 326 adults who had received prior chemo in the past five years for a “solid tumor” like lung or breast or colon and in contrast to “liquid tumors” like leukemia and multiple myeloma. It focused on attitudes toward chemotherapy before and after actually receiving it. 

   It probably doesn’t surprise people that 83% of participants reported being at least “somewhat fearful” about chemotherapy beforehand, but after receiving it 62% reported having had misconceptions about it and only 38% felt that their fears were justified.  It wasn’t completely trivial: 94% of patients reported some side effects, but only 14% reorted that chemotherapy was very difficult.  In contrast, nearly one third (32%) felt that chemo was easy or even very easy for them.  Importantly, 90% of those surveyed noted that chemo gave them hope, and 94% would recommend it to someone else with cancer who had been recommened to receive chemotherapy. 

  Part of the focus was also on communication about the treatment plan.  Only 44% of patients received written materials about their chemotherapy plan before treatment, while 78% who did not felt that a written plan would have been helpful.  A treatment plan was given to 35% of patients after their chemo had been administered.  Better communication appeared to improve the level of comfort that patients had with the chemo experience. 

   The survey is part of a larger survivorship program called Surviving with Confidence that includes a video of real patients discussing their cancer, chemotherapy, and survivorship issues that have followed.  This free video is available here.

   I think it’s important to emphasize that patients are all unique in not only their health but also their attitudes and tolerance of side effects, and chemotherapy options are as varied as different kinds of food.  It’s not appropriate to oversimplify that “chemo is well tolerated” any more than it is to presume that chemo is terribly punishing.  But for people who are wary about the feasibility of taking chemo, input from other patients who have been there should count more than my opinion, as someone who has never received it and who gives chemo for a living. 

   So for those of you who have experienced chemo directly, do the results of the survey resonate with you?

   One of the novel agents being studied in lung cancer is sutent (sunitinib), a multi-targeted oral anti-angiogenic drug that I’ve described in a prior post.  While I’ve mentioned a small study I’m leading at my own institution with this agent in advanced NSCLC patients with bronchioloalvelar carcinoma (BAC) or who have never smoked (information here), I wanted to describe a couple of larger studies that are being run by Pfizer, the company that is developing sutent, in lung cancer.  Their development program is a series called the SUN trials, for Studies to UNderstand Sunitinib, another acronym that is a bit of a stretch in order to be memorable.

   These trials are based on the combination of sutent/tarceva, which has been studied in a limited trial in kidney cancer (abstract here), and another one in NSCLC is being conducted at the University of Wisconsin (information here).  

   The largest trial is SUN-1087, which is an international phase III randomized trial of the combination of sutent and tarceva (erlotinib) compared to a current standard for previously treated patients with advanced NSCLC of tarceva with a placebo.     The SUN-1087  trial is ongoing and will plan to enroll 956 patients in the second or third line setting, and it patients with any kind of NSCLC (adenocarcinoma, squamous, or less common subtypes).  It will look at potentially important variables such as whether enrolled patients received prior avastin (bevacizumab), whether they are a never-smoker, ex-smoker, or current smoker, and also their EGFR status (I believe my looking at immunohistochemistry, the levels of EGFR protein on tumor cells.  These factors will be monitored and compared between the two arms so that neither arm receives far more never-smokers, prior recipients of avastin, etc.  –  a balancing act called stratification.  The tarceva will be given at the standard starting dose of 150 mg daily, with sutent at 37.5 mg daily, and the trial will treat all patients until they develop either progressing cancer or prohibitive toxicity.   The goal of the study will be to see whether the tarceva/sutent provides a significant overall survival (OS) advantage over tarceva alone (with tarceva).  Further information on this trial, including participating sites, is available here.

   A smaller trial known as SUN-1058 has a very similar design of tarceva/sutent vs. tarceva alone, but it doesn’t have a placebo included.  It is enrolling essentially the same population of previously treated patients with advanced NSCLC (second and third line), with any NSCLC subtype, but will only enroll a total of 126 patients and will be looking at progression-free survival (PFS) as the primary endpoint.  Further information on this trial, including participating sites, is available here.

   You might ask yourself why a company would conduct two trials with such similar designs – it’s not a typical approach, and I’m still not sure why the company would do this.  However, I speculate that the reason for running a small trial at the same time as a large trial is a strategy to obtain early feedback from a small trial looking at PFS (a quick endpoint) that could potentially lead to changes or an early termination of the larger trial looking at the longer-term endpoint of OS before having invested far more millions into the larger trial.  (more…)

   Completing the analysis of the randomized trial that compared alimta (pemetrexed) and taxotere (docetaxel) in second line  treatment of NSCLC (abstract here), which showed nearly identical response rates and survival but a more favorable side effect profile with alimta, another retrospective review of results looked at differences between the arms in older vs. younger patients (abstract here).

   Typically, the trial enrolled only a minority of patients 70 and older, who accounted for only 86 of the 571 patients on the study (15%), despite the fact that the median age for patients newly diagnosed with lung cancer in the US is now just over 70.  Besides age, they didn’t differ significantly in performance status, NSCLC subtype, or other variables from the younger patients.  There were also no clear differences between the older patients who were randomized to taxotere vs. alimta.

   The trial as a whole showed no differences in efficacy between the two drugs, and that was true for the 85% of patients who were under 70.  But in the patients 70 and older, there was a better progression-free survival (PFS) and overall survival (OS) in recipients of alimta:

 (Click on images to enlarge)

By the numbers, median PFS in patients 70 and older was 2.9 months with taxotere and 4.6 months with alimta; for OS, the numbers were 7.7 and 9.5 months, respectively.  One year survival numbers weren’t different, 23.1% vs. 20.4%.  (more…)

   One very important trial that has changed how we treat previously treated patients with advanced NSCLC has been a trial coded JMEI by Lilly, which sponsored this phase III randomized trial that directly compared second line treatment with alimta (pemetrexed) against the only FDA-approved second line treatment at that time, taxotere (docetaxel).  Essentially identical in activity, this trial led to alimta’s approval for lung cancer because it was associated with less frequent and severe drops in blood counts and fewer hospitalzations than with taxotere (abstract here).  But from this trial we’ve also been able to glean additional information on who benefits more or less from second-line treatment.

   Dr. Glen Weiss published a follow-up paper (available here) that analyzed several variables in the JMEI trial.  Some findings were definitely anticipated: patients with the best performance status of 0 had a far better survival than patients with a modestly or more significantly compromised performance status of 1 or 2 (median survival 12.7 vs. 8.3 vs 2.6 months for 0/1/2, respectively) — we knew that healthier patients do better and live longer. 

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  I’ve described mediastinoscopy as a “gold standard” preoperative procedure in patients who are candidates for surgery.  Although it’s controversial whether patients with a very low likelihood or a very high likelihood of cancer in the mediastinal nodes (mid-chest, between the lungs) need to have this confirmed by obtaining tissue to review under a microscope, we strongly prefer to get tissue for patients in whom this is a reasonably open question.  For patients who are good surgery candidates and in whom there is no evidence of cancer in the lymph nodes of the mediastinum, surgery is the preferred next step.  For patients who are good surgery candidates but have lymph node involvement confirmed on the same side as the main cancer (N2 nodal involvement), we most commonly recommend chemo and sometimes radiation before pursuing surgery, or recommend chemo and radiation without surgery.  And for patients who have cancer in the mediastinal lymph nodes on the side opposite the main tumor (N3 nodal disease), we generally recommend chemo and radiation rather than a surgical approach.  Why the difference in management?  Because as nodal stage increases, the risk of cancer recurrence outside of the chest becomes greater, meaning that we need to think about distant disease (and chemo to cover it) more and more, because even excellent local treatments like surgery or radiation, or both, just can’t address micrometastatic disease outside of the treatment area.

   While the gold standard has been mediastinoscopy, it’s invasive and requires general anesthesia.  Serious complications are rare, but it’s not a trivial procedure either.  And it’s very difficult to do a repeat mediastinoscopy to assess response to induction (pre-operative) chemo or chemo/radiation if a prior mediastinoscopy was done for initial staging.  So having another option for getting tissue from mediastinal lymph nodes, especially if it is minimally invasive, would be very welcome.

   One of these options that is gaining traction uses endoscopy, a tiny camera on the end of a tube, which can be used to look down the esophagus at the stomach (”upper endoscopy” or EGD, for esophagogastroduodenography), or the bronchial tree of the lungs (bronchoscopy).  These procedures usually just require sedation, don’t require any incisions, and don’t leave visible scars.  An endoscope can have an ultrasound probe attached to it so that a trained physician can get an idea of the shape and size of things behind visible barriers, allowing them to find enlarged lymph nodes that may be behind the walls of the esophagus or bronchi.  The endoscope also includes a needle that can be injected into a suspicious node or tumor within the bronchus. 

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   One of the members of GRACE’s Board of Directors who isn’t an oncology person asked me for a recommendation for a general book on cancer for the public.  I didn’t have a good answer, because most of my reading has been for physicians, but it’s a great question.  I like to think that we and the internet provide a lot of very helpful information for patients, but there are some books that can provide a very good overview of multiple cancers, a huge range of cancer topics, and also some books dedicated just to specific cancers like lung cancer. 

    Because I actually haven’t read these in any detail, I’d consider them more of a wish list of books I’d like to get to, and/or get some opinions from people who have read these carefully.  I’d like to learn what books people have found the be the best resources, and perhaps we can add them to the sections on “other resources” in the new website, so please add your comments (they’re back up):

   Everyone’s Guide to Cancer Therapy (5th Ed) is written by specialists on each topic, largely at Univ. of California, San Francisco.  It has received great reviews on Amazon, and my read of much of the lung cancer chapter (at least, a good skimming) really showed that it was a very good general review, with less detail than we’d include here, but a very nice, brief summary — and I think pretty easy to find a few pages on what you’re looking for.  Probably a great resource if you want a book of general cancer information and have family members affected by different types of cancer. (more…)

  We’re back up, so people can leave comments after these posts, register, etc.  

  The plan is to move over the all of the post content to the GRACE website, and then start a new forum section there, freezing the OncTalk forums so that they can be read and searched, but not added to.  Instead, a very similar forum structure has been started in the GRACE website, separated by “verticals”, so that questions about drug side effects can be attended to not only by me and Dr. Laskin but also Dr. McCune, a Pharm D, radiation oncology questions can be fielded by expert radiation oncologist Dr. Vivek Mehta, and other questions can be covered by the most qualified expert(s).  The division by subject will also exist with the articles/blog content the faculty provide, so people can find multiple posts about radiation oncology or social work/coping with cancer all together.

   I expert that there will be some tweaking to do once we move, so please provide your suggestions.  We can always continue to improve it. 

   But expect that sometime in the next week or so you’ll be directed over to the posts at GRACE instead of OncTalk, and from the OncTalk discussion forum to the forum at GRACE to add new entries.  Please jump in when the time comes.  We will likely auto-redirect the web browsers at some point in the future, once the kinks are ironed out (most, at least).

Thanks to member Carlos for bringing to our attention a high profile article in the New York Times today about some controversy now surrounding the Early Lung Cancer Action Project (ELCAP) trial, probably the most influential study of CT screening that has been done. Let me disclose immediately that my own institution, Swedish Hospital in Seattle, is a participating site in ongoing CT screening work led by Dr. Claudia Henschke and the group at Cornell Weill Medical School in New York.

It’s hard not to discuss the idea of CT screening for lung cancer without mentioning Dr. Henschke, who I would say has been the leading and most visible proponent of lung cancer screening in the entire medical community. She has led work in this field for many years, and her paper published in late 2006 (abstract here) reported an 88% 10-year survival, remarkably different from the typical overall survival for lung cancer without screening, which is closer to 15%. And while many experts noted major flaws in extrapolating that one could expect anything close to that in the real world, the trial represents one of the strongest points in favor of CT screening for lung cancer.

The brouhaha stems from the new discovery that much of this work, particularly early on, back in 2000 or so, was actually being funded by the tobacco industry, and there’s some suspicion that the leaders at Cornell may have been less than forthright about the source of funding, since the tobacco money was used to start a new foundation that was not appreciated to have been tied to the tobacco industry.

And why would the tobacco industry have a stake in this? Presumably, if people felt reassured that we can detect lung cancer early enough to cure it most of the time, people would feel less of a compulsion to stop smoking, or maybe even pick it up as a habit. Yikes. (more…)

  I was reminded of the important topic of occult N2 NSCLC by a comprehensive review that just came out in the Journal of Thoracic Oncology (abstract here) by a friend, thoracic surgeon Frank Detterbeck, who leads the thoracic oncology program at Yale.  To review the basics of lymph nodes for lung cancer, N0 means no lymph nodes are involved; N1 means that lymph nodes are involved on the same side as the primary cancer and inside the confines of the lung; N2 nodes are in the middle of the chest, in the mediastinum, which is between the lungs, and on the same side as the main cancer; N3 nodes are involved and on the other side of the mediastinum or above the clavicles.  Lymph nodes beyond those points are M1, or metastatic sites, and would be treated as advanced lung cancer.  Occult N2 disease is also sometimes called unsuspected or surprise N2 disease as well, and it refers to a surprise upstaging of patients who were thought to have stage I or II NSCLC before surgery, but after the operation, there’s evidence that one or more mediastinal nodes are involved.

  For NSCLC, one of the important aspects of staging in patients who don’t have obvious stage IV disease is staging, which is done largely based on scans, but getting tissue from mediastinal lymph nodes is a controversial central feature.  However, I think the controversial nature is whether it’s definitely needed or recommended for patients who have what appears to be a stage I lung cancer (in whom the likelihood is so low it’s not definitely needed), or who have imaging that is very, very consistent with cancer in the mediastinum (in whom the likelihood is so high it’s not definitely needed).  In between are many potential surgical candidates with larger stage I, or stage II, or not entirely clear but likely stage III NSCLC.  In such patients, most well trained thoracic surgeons will try to get tissue with a mediastinoscopy (or other approach, like a transbronchial ultrasound or transesophageal ultrasound, both of which can sample mediastinal nodes) before surgery, because we know that outcomes are not good with surgery alone for such patients, and our standard is to give chemo or chemo/radiation before possibly proceeding with surgery.  However, some surgeons don’t do mediastinoscopies, even in cases with enlarged mediastinal nodes or other features that should suggest a high index of concern (you can’t find a fever if you don’t take a temperature).  You’ll never lose surgery business if you are willing to do surgery indiscriminately, on people who shouldn’t as well as should have surgery.  They may feel that surgery is the most important factor, so it’s worth just pressing forward and dealing with the outcomes later.  That’s below the standard of care, but that’s exactly what happens all too often, particularly when surgeons who aren’t specially trained in thoracic surgery do lung cancer resections.  What is worse, sometimes during the surgery, they don’t bother going into the mediastinum to look for nodes (this can be done as a mediastinal dissection during the larger operation, if not as a separate mediastinoscopy procedure from the lower neck, going below the sternum (breastbone).  

   I’ll just emphasize that selection of a well trained and careful thoracic surgeon is extremely important in managing stage I - IIIA NSCLC.  A poorly trained or just not motivated surgeon can do a remarkable disservice to a patient and sabotage their best opportunities for good results, and a well trained and thoughtful thoracic surgeon can maximize that.  I say that as a non-surgeon.  There should be a book on “When Bad Surgery Happens to Good People”.  However, even if patients are treated exactly by the book by a great surgeon or oncology team, sometimes you find unsuspected mediastinal disease at the time of the full surgery, even in patients whomay have had a negative mediastinoscopy (which is a sampling, not an exhaustive search for nodes) before surgery. (more…)

Just a light-hearted reminder that it could always be worse.  Although I think this comic says it better:

   Perhaps a tad off-topic, but we’ll get back to cancer momentarily.

Enjoy the day and have a chocolate bunny.

   As I’ve described in various posts about targeting the epidermal growth factor receptor (EGFR), one of the main signals that is important in many lung cancers, there are agents like gefitinib (iressa) and erlotinib (tarceva) that target the internal switch that triggers activity inside the cell, and there are agents like cetuximab (erbitux) that work on the external front end receptor to block activity:

(Click on image to enlarge)

I must admit that I’ve always been curious whether combining these two appoaches, giving an oral EGFR tyrosine kinase inhibitor (TKI) with a weekly IV EGFR monoclonal antibody would potentially provide a synergistic inhibition and impressive activity.  For the first time, Ramalingam and colleagues have published their limited experience of combining iressa and erbitux in a small trial of patients with advanced NSCLC (abstract here).  Unfortunately, the results don’t look particularly impressive.

   My friend Dr. Ramalingam has just recently moved from Pittsburgh to head the lung cancer program at Emory University in Atlanta, but while at the University of Pittsburgh he and colleagues there conducted this study to assess the safety and get a sense of the activity of a combination of iressa with erbitux.  Iressa, the first EGFR TKI approved for NSCLC, was studied at the previously approved standard dose of 250 mg daily (subsequently found to not be significantly superior to placebo in a large trial of previously treated patients with advanced NSCLC and taken off the market).  Erbitux was given at increasing doses, starting at a rather low dose and escalating to a point of maximum safe/tolerable dose for the combination.   For these “phase I” trials of safety, small numbers of patients are usually enrolled.  This study included 13 patients who had received at least one prior chemo regimen for advanced NSCLC.

   Although the numbers were small, there were no responses seen, and only 4 patients (31%) even showed stable disease.  Progression was pretty quick, and 3 patients developed severe declines in blood magnesium levels, which is a known side effect of erbitux, but this was a high rate. 

   The investigators also tried to do some molecular studies from the subset of 10 patients who had some tissue to work with.  They didn’t find any EGFR mutations that would be expected to be associated with robust EGFR TKI responses.  They also did not detect any RAS mutations that are generally recognized as being very unlikely to show a response on EGFR TKIs.

   There are many reasons why this little study is far from the definitive word on the subect.  Iressa at the dose tested is not as effective as tarceva, so perhaps the results would have been more favorable with tarceva.  Perhaps these results just happen to be particularly disappointing in a small number of patients who happened to not benefit, but a larger study would have shown better results that represent reality better.   Or maybe this combination isn’t particularly useful in a general population but could be very impressive in a more selected population, based on EGFR mutations or never-smoker status.  I’ve also wondered whether adding erbitux to tarceva in a patient who has now become resistant to tarceva after a prior good response would restore activity.  But we don’t have any evidence on any of these questions.

   For now, I think all we can say is that a combination of EGFR TKI and monoclonal antibody doesn’t lead to blockbuster activity in NSCLC.  But expect to see a lot more trials of targeted agents in coming years.

    For nearly 18 months now, I’ve been trying to write about complex medical issues in an accessible way that still covers the difficult nuances and shades of gray of these topics.  I try to show and weigh the evidence, and when I don’t have an evidence-based answer, I offer my thoughts with the caveat that there are other views and judgment is required.  And you know what?  Plenty of people seem to be happy to get more sophisticated answers than just the fluff sound bite coverage of a topic. 

    So what would be the opposite of OncTalk?  A grossly underqualified person who provides a glib, wildly oversimplified and sensationalized distillaton of a complex topic into a digestible candy morsel of information.  I think that the teaser on the 11 pm news about every “new breakthrough for cancer” because someone killed cancer cells in a test tube by drowning them in ketchup is a real problem.  These snippets are so from being a useful treatment that it leads people to have unrealistic expectations and distracts them from the real and useful information that consumers should be gathering.  I think it’s a tragic disservice to sensationalize and oversimplify health care information, especially about major issues like cancer, that lead to false hope and misunderstanding of options among difficult medical choices. 

    An article today that came from a source called HealthDay blared “Frying Tumors Can Boost Lung Cancer Survival“, and this was picked up by several mass media franchises (member dadawg001 asked about it here).  Now, I imagine that Amanda Gardner, the reporter who sings the praises of radiofrequency ablation (RFA) here, is a nice person, but this is a silly piece of puffery.  Moreover, I haven’t seen her at any of the cancer meetings, and I would love to know what qualifications she has to education the general public on how to treat their cancer.  The report isn’t about a trial comparing people who were randomized to receive either RFA to surgery or radiation, which would be more conventional approaches.  It was (as far as I can tell, with almost no actual content provided) just a single institution trial of some number of patients, who very well might have had the same or better survival with no treatment at all or with standard radiation.  The comments that followed are by Dr. Damian Dupuy, who has done more of this work than just about anyone else (see prior post).   That makes him the single person who I would predict to be more biased in favor of RFA than anyone else in North America.   He suggests that the medical establishment is way behind the times in not recommending this approach routinely.   I think my kids are beautiful too. 

    By the way, this work is being presented at the annual meeting of the Society for Interventional Radiology, so basically the people who make money by doing RFA think RFA should be done more often.  Hmmm — why didn’t I didn’t read anything in all this about the FDA warning on the basis of the excess numbers of deaths they’ve had reported from people doing RFA on lung tumors (see prior post)? 

    Don’t I administer chemo for a living?  Sure, but this site is dripping with evidence from comparative trials to support what we’re doing, and I happen to spend a huge portion of my waking life trying to provide a thoughtful perspective to people here, for no financial gain.  Let’s keep the PR marketing out of this.  It annoys me when companies push out press releases about their new wonder drug being the cure for cancer based on a study with 40 patients, or people make unjustified claims about Mangosteen, or the newspaper runs a sound bite about the next great thing. 

    It’s not that I don’t think RFA could be helpful.  It just needs to be studied carefully, and if it proves to be better than what we’re doing, I’ll be the first to publicize and recommend it.  But poor readers might presume that HealthDay actually knows something about health and not just hyping the latest story, or that the reporter for this article is remotely qualified to discuss this topic. 

    I’ve actually been thinking that GRACE should give out honorary awards for the most idiotic news reports each year, like the Razzies that award the worst actors and movies each year.  This would be a way to try to elevate the level of discussion by highlighting and embarassing the people who have done the greatest disservice each year to the cancer community by irresponsible journalism.  

   Sorry to rant.  It’s just that the whole mission of what we’re doing is to try to provide detailed education, and garbage fluff news reports are like painting over a nice neighborhood mural with graffiti.  Sure, it’s more paint, but is it better?

   We’ll probably never do something as caustic (but cool) as the Annual Most Irresponsible Medical Journalism Awards.  We don’t have time to sift through the many choices anyway.