Though there are many presentations to discuss in the wake of ASCO, we’ll need to pace ourselves on these.  I and some of the other faculty members will offer thoughts on some of these in the coming weeks, and we also have our upcoming post-ASCO review on June 23rd (click here to learn more and sign up for this free online program).

Today we saw the results of a couple of long-awaited trials of treatment approaches that represented a couple of the more promising concepts for moving forward in our treatment of extensive SCLC, and I’ll cover the first of these today (though only with the benefit of my notes, rather than as many details as I’d like, so these comments are subject to revision and added details later).  Amrubicin has been the subject of some prior  discussion here, but that discussion focused on smaller, phase II trials; we’ve needed the results of a randomized phase III trial that directly compares the chemo agent amrubicin as a single agent to our current standard for Hycamtin (topotecan).  The ACT-1 trial in enrolled 637 patients with extensive disease SCLC who had all received first line therapy and then relapsed — the trial included patients who had a “sensitive” relapse, 3 or more months after prior chemo had ended, as well as “resistant” relapse, which is marked by progression within 3 months of prior chemo ending (pretty evenly split at nearly 50/50 on the trial).  Patients were randomized 2:1 to either amrubicin at 40 mg/m2 IV on days 1-3 of a 21 day cycle, or topotecan at 1.5 mg/m2 IV days 1-5 of a 21 day cycle.

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   Here is the discussion about the study of picoplatin vs. placebo for relapsed SCLC, from the post-ASCO review that I did with Dr. Pennell.  Unfortunately, this work was an overall disappointment, not quite beating placebo in a setting for which we already have a more active alternative.  Here’s the transcript and figures from that portion of the discussion.

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Dr. West: So we’ll turn to the SPEAR trial.  This is a small-cell study with picoplatin which has been one that has been on the radar for small cell for several years at this point.  And this is a randomized trial, a 2 to 1 randomization, of patients who had previously received chemotherapy for extensive small-cell lung cancer, and this was for patients who had relapsed within six month,s with the thought being that the patients who actually progressed beyond six months would often get their prior chemo instead.

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   So patients were randomized to picoplatin with supportive care or one third of patients getting supportive care alone, and the trial looked primarily at overall survival. 

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This is the second of two parts in the Reference Library by Dr. Gadgeel on small cell lung cancer.

Patients with Limited Stage Small Cell Lung Cancer

As stated in the prior chapter from the reference library on basic principles and workup of small cell lung cancer (SCLC), in patients with limited disease (LD)-SCLC, the cancer is only detected in the lung, or the lung and the lymph nodes. But even if it is only detected in these sites it is known, based on prior studies, we remain concerned that the cancer has spread to other parts of the body but that it has not yet grown in these other sites for it to be seen on the scans.

It is for this reason chemotherapy is always included in the treatment of LD-SCLC . Chemotherapy goes throughout the body and therefore will not only attack the cancer visible in the primary lung tumor and the lymph nodes, but also the SCLC cells in the other parts of the body that may exist but remain invisible on the scans.

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General Introduction to Small Cell Lung Cancer

Lung cancer consists of two major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 85% percent of all lung cancer patients have NSCLC,  and the remaining 15% have SCLC.

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In 2010, the American Cancer Society has estimated that approximately 222,000 new cases of lung cancer will be diagnosed, of which 35,000 will have SCLC. Even though both subtypes are lung cancers, they are considered as separate diseases in most ways, and the management of these two cancers is different. It is important to recognize that the treatments applicable for NSCLC, including many newer agents that have been approved and are the subject of increasing research and media attention, are not clearly relevant for patients with SCLC.

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Here is the last case I discussed several months ago with Dr. Nasser Hanna, lung cancer expert at Indiana University.  After two cases that included never or light former smokers, which he joked that I saw far more of than he did, we changed direction to cover current issues in managing extensive stage small cell lung  cancer, a field in which he’s been a leader.

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Dr. West: Let’s turn to a final case: a 57-year-old currently smoking woman, with a 50 pack year smoking history, who first developed malaise and a cough about 6 months prior to her presentation.  She felt her symptoms may have spontaneously improved transiently, but 6 weeks prior to her presentation, she developed non-exertional left chest pain and slight hemoptysis.  She was not short of breath, had no weight loss, and she presented to her primary care physician and was found to have an abnormal chest x-ray followed by a CT.

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Here’s the podcast from a webinar I did last month with Dr. Weiss on the subject of whether patients with very limited small cell lung cancer (SCLC) should perhaps undergo surgery as a first intervention.  Historically, surgery isn’t considered as a typical treatment for patients with SCLC, even if it’s very early stage, but some results from retrospective experiences suggest that the patients who undergo surgery in this setting do very well.  While that’s true, the central question is whether they do well because they receive surgery or because they had a very unusual SCLC that was able to be detected so early.  This podcast covers the evidence and the lingering questions about this topic.  Along the way, it also provides some discussion of the general characteristics of SCLC.

Here’s the audio and video versions of the podcast, along with the figures and transcript for the program.

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west-surgery-for-limited-sclc-figures

west-surgery-for-limited-sclc-transcript

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Podcast: Play in new window | Download

   The development of targeted therapy drugs has improved survival for patients with NSCLC, and the “pipeline” of agents in development awaiting further testing in clinical trials seems to be increasing by the day.  The improvements in survival in particular subpopulations of patients with NSCLC inspires both patients and physicians who treat lung cancer to hope that similar gains may be made, perhaps incrementally, for patients in all subpopulations of NSCLC.

    In contrast, progress in small cell lung cancer (SCLC) has been disappointingly slow.  Although there was hope initially about improved survival with the combination of cisplatin and irinotecan over the “old standard” of cisplatin with etoposide based upon a trial in Japan, two randomized trials in a more heterogeneous North American population, one trial community-based and another conducted by SWOG, failed to show any survival advantage.  The greatest gains we have thus seen recently for patients with SCLC come from radiation, with twice daily radiation improving survival for patients with limited-stage disease (for those patients who may be able to tolerate the increased toxicities) and prophylactic cranial irradiation (PCI) improving survival for patients with extensive stage disease.

   This frustrating lack of improvement from a chemotherapy front does not come from lack of effort. Much like for NSCLC, a large number of targeted therapy drugs have been tested in SCLC, but with no major breakthroughs.

   But lung cancer doctors are by definition optimists, and we are always hopeful that breakthroughs that make real differences in the lives of our patients may be just around the corner. One of the active areas of research involves BCL-2 inhibitors. BCL-2 is a protein involved in cell survival, and is overexpressed in many cancers, including SCLC. Overexpression of BCL-2 helps to protect a cancer cell from dying, and increased levels of BCL-2 expression help make a cancer cell more resistant to chemotherapy.

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A few weeks ago, I gave a talk at a Seattle non-profit called Cancer Lifeline, at which I described some of the highlights of current lung cancer treatment and the direction of ongoing research.   I recorded that lecture (which does include some stray sounds in the background), and I thought it would be helpful to make it available to people online.

The talk lasted over an hour, so we’re breaking it up into pieces on a discrete topic.  The first one is on SCLC and specifically relapsed disease, where I focused primarily on work with amrubicin.

Here is the slide set, the transcript, a link to the audio (mp3) version, and then the video podcast presentation.  More topics to come.

cancer-lifeline-talk-part-1-sclc-figures

cancer-lifeline-talk-part-1-sclc-transcript

Audio version Cancer Lifeline Talk Part 1 SCLC

Podcast: Play in new window | Download

  I recently had the opportunity to sit down with Dr. Toni Wozniak, Moedical Oncologist and lung cancer expert at the Barbara A. Karmanos Cancer Center at Wayne State University in Detroit, MI.  We covered several topics, including SCLC, the subject of this podcast. It is an audio interview but includes a few figures that are synchronized with the audio on the video version, or you can download the pdf of the figures and just follow along with the audio.

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    As with some prior podcasts, it’s primarily audio, but with some synchronized figures that pop up on the video version, or you can download a pdf file with the images to go with the audio.  There’s also a transcript available to download.

Wozniak SCLC figures

Wozniak SCLC Transcript

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Podcast: Play in new window | Download

    Several years ago, I participated in a clinical trial with a combination of carboplatin and irinotecan for treatment of extensive SCLC, just now being published (abstract here).   As a bit of background about the potential utility of irinotecan, the well established cornerstone of treatment of extensive SCLC for about two decades has been a platinum agent (cisplatin or carboplatin) with etoposide, but an important trial in Japan suggested that a cisplatin/irinotecan regimen may be superior to cisplatin/etoposide (abstract here).  Subsequent work done in the US did not support that conclusion, and one leading consideration is that there are meaningful differences in the activity and side effect profiles of different chemotherapy drugs in different racial populations, due to factors like the enzymes that alter metabolism of these agents.  Nevertheless, irinotecan and its cousin topotecan are still high on the list of drugs most active in SCLC.

    The clinical trial in which I participated combined irinotecan with carboplatin, the alternative to cisplatin that is often substituted because of generally comparable activity and a more favorable side effect profile.  In this trial, both agents were given IV on a single day every three weeks.  There were two different groups of patients enrolled, with 40 patients in each: one had received no prior treatment for extensive SCLC, and the other had previously received first line chemotherapy (with cisplatin or carboplatin and etoposide) and had now relapsed.  For the group that had received prior chemo, a lower dose of irinotecan was given (150 mg/square meter vs. 200 mg/square meter every three weeks).  Patients received up to six cycles of this combination.

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