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Small cell lung cancer (SCLC) has been a very challenging disease for patients and physicians, and unfortunately one in which our improvements in treatment have been few and far between. In fact, a recent educational session at ASCO was titled "Small Cell Lung Cancer: What's New Since 1978?". The decreasing frequency of SCLC has also made it increasingly difficult to study, but even when the studies are completed, many emerging potential therapies have proven to have no benefit.
But there is a glimmer of hope on the horizon. A drug called amrubicin, which is a type of chemo drug called an anthracycline, with multiple DNA damaging effects on cells. Amrubicin is metabolized to amrubicinol, an active metabolite with 5-200 times the inhibitory effect of the original drug.
Amrubicin has been in development by a Japanese pharmaceutical company since 1986 and has actually been approved for commercial use there for both SCLC and NSCLC since 2002. Two recent trials with amrubicin as a treatment for previously treated SCLC for Japanese patients were presented at ASCO last year, and they looked quite encouraging. One has since been published by Onada and colleagues from the Thoracic Oncology Research Group in Japan (abstract here). In this study, 60 patients who had progressed after at least one line of prior chemo therapy for SCLC (44 with sensitive disease that took at least 60 days after last chemo to progress, 16 with resistant disease that progressed sooner than that) received amrubicin as a 5-minute IV infusion at 40 mg/m2 on days 1-3 every 21 days. Remarkably, the response rate was about 50% in both the sensitive and resistant patients, with an encouraging median survival that exceeded 10 months in both groups.
In keeping with prior experience with this agent, amrubicin was well tolerated, with the leading side effects being low blood counts, diminished appetite, and fatigue. Another, smaller Japanese trial with amrubicin for patients with previously treated SCLC was also presented at ASCO (abstract here) but hasn't yet been published. This study included 34 patients (24 with sensitive disease, 10 refractory) who received a slightly higher dose of 45 mg/m2 IV days 1-3 every 21 days. This was associated with a complete response rate of 11.8%, and a partial response rate of 41.2%, for a total response rate of 53%, which is quite amazing. The median survival on this trial was just over 9 months. The toxicity profile was very similar, primarily with low blood counts.
How good are the results of these studies? The response rates for topotecan in previously treated small cell lung cancer are generally in the 20% range, and the median survival is several months less. However, it would be great to see results this encouraging from outside of Japan, not because we don't trust them, but because we know there are significant genetic differences between Japanese patients and US or European populations, at least. Thus far, we haven't seen the very favorable results with irinotecan in the US that were previously seen in Japan. So these results need to be replicated outside of Japan, and we need to gain greater experience with determining the optimal schedule and ensuring the safety in the setting of low blood counts.
There are several trials being conducted now. In Japan, a randomized trial of 130 elderly patients with SCLC is being conducted, comparing amrubicin to carboplatin-etoposide (information here). An international, but still small trial of just 81 patients with previously untreated SCLC will test amrubicin with or without cisplatin (information here). In the UK, a trial of amrubicin, with or without cisplatin, is being compared to cisplatin/etoposide for patients with newly diagnosed extensive SCLC (information here). In the US, there is a phase II trial for previously treated SCLC in which everyone receives amrubicin (information here), another small phase II trial randomizes patients with recurrent SCLC to amrubicin or the current standard of topotecan (information here). These are still small trials, but they'll help us learn if amrubicin is as useful around the world as it appears it may be in Japan for patients with SCLC.
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