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Can Smoking Cessation be a presenting symptom of lung cancer?
I missed part of the presentation of the SATURN survival data at the World Lung Conference to hear a very provocative presentation by my cross-town colleague, Dr. Barbara Campling. I know and respect Dr. Campling from her time at the Philadelphia VA, where she took excellent care of veterans with lung cancer for many years. At thoracic tumor board, she could always be counted on to ask about a lung cancer patient’s smoking and smoking cessation history.
For years, we have known that lung cancer patients often quit before their diagnosis. Although we don’t talk much about it, we’ve known for some time that the risk of lung cancer exceeds that of continuing smokers for a few years after quitting. The predominant view of this phenomenon is that many patients quit before diagnosis because of early symptoms of their lung cancer. A minority argue that maybe smoking cessation can even cause lung cancer.
Dr. Campling made some observations that made her question these hypotheses. She saw that many of her patients quit smoking before their diagnosis, and before they even felt symptoms related to lung cancer. In talking to her patients who had quit, some of them reported that even thought they were once heavy smokers and very addicted, they found quitting effortless. One patient reported that he woke up one morning and just forgot to have his morning cigarette. Any of you who have been truly addicted to nicotine or anything else know that you don’t just forget to smoke. So, as a good scientist does, Dr. Campling asked if there was something else going on.
Dr. Campling interviewed 115 lung cancer patients about their dates of cessation, onset of symptoms, diagnosis, and degree of maximal addiction. For comparison, she also interviewed patients with prostate cancer and heart attacks. Prostate cancer served as a cancer control because it is one of the cancers least associated with cigarettes. Heart attacks served as another important control because it is a non-cancerous but smoking related health condition.
The data on the control groups, circled in pink below, was consistent with what is known about smoking and smoking cessation.
(Click on image to enlarge)
Dr. Shirish Gadgeel on Managing Locally Advanced NSCLC
Our next podcast slide presentation comes from Dr. Shirish Gadgeel, medical oncologist at Wayne State University in Detroit. He came out to Seattle for a physician education program I run and was kind enough to stay for our NSCLC Patient Education Forum, where he spoke on our Current Standards of Care for Locally Advanced (Stage III) NSCLC.
Here’s his presentation in audio and video formats, along with the transcript and copies of the slides.
gadgeel-management-of-locally-advanced-nsclc-transcript
gadgeel-management-of-locally-advanced-nsclc-figures
gadgeel-management-of-locally-advanced-nsclc-audio-podcast
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Never-smoker vs. “ever-smoker”? It’s not quite that simple…
For the last several years, we’ve known that never-smokers are more likely to have a significant and long-lasting response to EGFR inhibitors. Since then, we’ve learned that EGFR mutation status is quite correlated with smoking status and is the more important, likely driving factor, but all of this work has led to a new focus on never-smokers and smoking history in general. In fact, prior to about 5-10 years ago, we didn’t consistently record much of a smoking history for patients because it wasn’t appreciated as being relevant. Now, not only do we realize it’s an important factor, but we’re moving beyond the over-simplified view that smoking history is just a “yes/no” answer. We couldn’t expect that it would be that simple. Continue reading
Dr. Le, Radiation Oncologist from Stanford, on Radiation Options for Early Stage NSCLC
Dr. Quynh Le, radiation oncologist and Professor at Stanford University, was kind enough to participate in our NSCLC Patient Education Forum. She spoke on the topic of emerging treatment options using radiation for early stage NSCLC. The new work she’s describing on stereotactic body radiation therapy (SBRT) is looking promising enough that it’s being considered increasingly as a very strong choice for people with localized lung cancer but who aren’t good candidates for surgery or are disinclined to pursue it. In fact, much of the debate in the lung cancer community is about whether SBRT appears compelling enough to be considered as a viable alternative to surgery even in patients who are fine candidates for resection.
The podcast and additional materials from her presentation are here:
Q Le Radiation for Early Stage NSCLC Audio Podcast
q-le-radiation-for-early-stage-nsclc-figures
q-le-radiation-for-early-stage-nsclc-transcript
Some passages of the program may be a little difficult to follow, so please use the transcript if you need to clarify parts. You can also ask questions here, for clarification or follow-up. I hope you find it helpful.
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Avastin, Radiation, and Tracheoesophageal Fistulas: Yet another Cautionary Tale
Look, before I begin this post let me say that I’m really not trying to be a negative person when it comes to Avastin (bevacizumab; see here and here). It is a great drug in the appropriate setting, and is has been proven to prolong survival in first-line treatment of advanced NSCLC patients when combined with chemotherapy. Given this success, as well as proven success in treating renal cell carcinoma, breast cancer, and colorectal cancer, it is understandable that people would keep testing it in new situations. It’s just that all of the recent publications that try and expand the role of Avastin to new areas seem to have disappointing results. Which brings me to today’s topic.
A new online publication in the Journal of Clinical Oncology by Dr. David Spigel and colleagues from the Sarah Cannon Research Institute in Nashville, TN, describes the experiences from 2 phase II trials in small cell (SCLC) and non-small cell lung cancer (NSCLC) using Avastin in combination with chemotherapy and chest radiation. There had been reports of safety concerns in the past with this combination, specifically with regards to something called tracheoesophageal fistula, but this was my own first look at the data.
A tracheoesophageal fistula is a pathologic connection between the esophagus (food pipe) and trachea (windpipe). It doesn’t take a doctor to imagine why it might be a bad thing to empty everything you eat or drink directly into your lungs, but in case you weren’t sure let me assure you this is what we in the business call “a bad thing”. It is always serious and often fatal, although if caught early can be treated with a stent that covers the opening and prevents passage of material between the two sites.
In 2006-07 there were two phase II trials enrolling patients to investigate the role of adding Avastin to chemotherapy and radiation in limited stage SCLC and in locally advanced (stage III) NSCLC. Concurrent chemoradiation represents the standard treatment for both of these conditions, so the only major change was in adding the Avastin. The SCLC study enrolled 29 patients, but stopped early after an unacceptable level of toxicity. In contrast, the NSCLC study only enrolled 5 patients before having to stop. I think these studies represent a cautionary tale, but are also a positive testament to the safety measures put in place to stop trials if they end up causing too much toxicity. Continue reading
Quitting smoking—it’s never too late
First, let me begin by thanking Kareena and Ned for an interesting and important conversation about the causes of smoking and the decline in risk from quitting. In this thread, debate arose about the nature of the decline in lung cancer risk after quitting, in particular whether it ever reached the same levels as a never-smoker.
One particularly good source addressing the question is the Nurses’ Health Study. This study observed 104, 519 female nurses over time then was analyzed to determine the increase in risk for various illnesses in smokers. As you might guess, the risk was increased for just about every medical condition that the investigators queried—total mortality, vascular disease, coronary heart disease, cerebrovascular disease, total respiratory disease, COPD, lung cancer, all smoking-related cancers, other cancers, colorectal cancer and other causes. The only factor that was queried without a statistically significant association was ovarian cancer.
Combating Nicotine Addiction with a Vaccine
Imagine that you’re a longtime smoker who is well aware of the health risks of smoking, not only in terms of lung cancer but also other cancers, heart disease, and other illnesses. You want to quit smoking, and perhaps you’ve tried several times, even trying Chantix, the nicotine patch, and other techniques. But in the end, it’s been hard to kick the pleasurable sensation of cigarettes. What if you could just remove that?
In fact, there’s a company called Nabi BioPharmaceuticals that is trying to harness the immune system to neutralize the reinforcing effect of nicotine. Anyone interested can see a few summary videos of their “NicVax” (Nicotine Conjugated Vaccine) concept , but the brief summary is that they’ve created a vaccine made of a nicotine derivative bound to a special carrier protein that, when injected, can teach the immune system to generate antibodies that recognize nicotine, bid to it in the bloodstream, and therefore block the ability of nicotine to cross through the blood brain barrier and stimulate receptors on brain neurons that release neurotransmitters signalling reward/pleasure. It’s injected a total of six times over six months.
An Uplifting Case: Tarceva after Iressa Led to a Great Response
I just wanted to tell people about a remarkable patient I just saw who is delighted to have had a remarkable response to Tarceva a few years after responding to Iressa. She made my day.
In truth, her case was remarkably long before this. She was diagnosed with bronchioloalveolar carcinoma (BAC) all the way back in 1995 (I was finishing med school, no kids — life was simpler then). She had undergone a left lower lobectomy for localized disease initially, but her cancer recurred in late 1998, confirmed on a bronchoscopy, and she began experiencing a cough then. She was initially treated with chemo and responded well for several years, with some changes in her chemo but generally doing well before being started on Iressa.
She recalls that within days of starting Iressa, her recurring cough improved dramatically, and she did well on it for over 5 years before her scans progressed and her cough worsened. She ultimately discontinued it back in May of this year, starting Alimta then. And though we might have hoped and expected that she’d show another great response, she actually continued to progress on that, with a worse scan and cough after two cycles. So this shows us that her cancer doesn’t quite respond to everything.
Molecular markers for chemotherapy—are we there yet?
“Are we theeeeere yet?” Every parent knows that familiar whining from the back seat of the car. Sometimes, I feel as impatient as the kid in the back of the car. Although EGFR mutation helps with predicting tarceva (erlotinib) response, I want markers for cytotoxic (traditional) chemotherapy now. Unlike the parent in the driver’s seat of the car, I’m not entirely sure where we are, or where we’re going. Sometimes I feel as though I’m driving in the dark. Could molecular markers be the headlights?
A new article in the Journal of Clinical Oncology brings us a few more miles down the road. I want to talk about the biocorrelates of the study, but the original point of the study is important enough to pull off our metaphorical road for some brief sightseeing. The investigators randomized patients with a performance status (PS) of 2 to chemotherapy with single-agent gemzar (gemcitabine) or gemcitabine plus carboplatin. Before proceeding, let’s review what PS2 means.
PS Definition
0 Normal activity – Fully active, able to carry out all pre-disease performance without restrictions
1 Symptoms but ambulatory – Restricted in physical strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (house work, office work).
2 In bed 50% of time – Capable of only limited selfcare, confined to bed or chair for more than 50% of the waking hours.
3 In bed >50% of time – Capable of only limited selfcare, confined to bed or chair for more than 50% of the waking hours.
4 100% bedridden – Completely disabled. Cannot carry out any selfcare. Totally confined to bed or chair.
As you can tell, these definitions are vague and broad. At any rate, they hypothesized that the addition of carboplatin would increase median survival from 2.4 months to 3.8 months. They wanted to power their study to have a 90% chance of finding this difference, if real, and calculated that they needed 220 patients to do it. Unfortunately, they only accrued 170 patients. More fortunately, the patients on both arms lived longer than expected– 5.1 months in the gemcitabine alone arm (yellow in the graph below) and 6.7 months for combined gemictabine and carboplatin (blue). The p value for this difference was .24, making this a negative study. However, like Popeye without his spinach, the study lacked power. So although the study didn’t pass the magic .05 bar and we can’t conclude that survival is superior with carboplatin, we also can’t conclude that they don’t do better. So, I’ll keep doing what I was doing before this study—personalizing therapy in this group to the individual patient at hand, with a bias towards using carboplatin in patients at the more functional end of PS2.
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