During the entire time I've been commenting on the most evidence-based and commonly used agents for previously treated patients, I've focused on taxotere, alimta, and tarceva (example in prior post here). In fact, that overlooks an agent that has actually been tested in a large study and been found to have similar activity to taxotere, but it remains pretty much an afterthought. The drug is topotecan, tested in an oral form that is just becoming commercially available; here I'll summarize the trial that illustrates that topotecan is a reasonable option but also suggests why it remains relegated to a lower priority than the other three options we tend to think of more readily.

At the ASCO meeting in 2005, Dr. Rodryg Ramlau from Poland presented the results of a large phase III international trial (ASCO abstract here) that directly compared oral topotecan to the standard of IV taxotere as a second line therapy for advanced NSCLC (subsequent publication abstract here). This study randomzed 829 previously treated patients enrolled from both Western and Eastern Europe to receive either taxotere at the typical dose of 75 mg/m2 IV one day every three weeks, or the altenative of topotecan by mouth at 2.3 mg/m2 for each of the first 5 days of a three week cycle. Treatment continued until there was evidence of progression or excessive side effects:

(Click on image to enlarge)

The study was designed to test whether topotecan was definitely inferior to taxotere or more or less similar, and it technically met the criteria to be considered not significantly worse than taxotere. However, at any given time point of follow-up, survival was better for the recipients of taxotere:

The response rate was 5% for both arms, which is just a little lower than some other studies of taxotere as second line treatment have shown.

The side effects of the two approaches were pretty comparable. While taxotere was associated with more frequent significantly low white blood cell counts (60% vs. 50%, so pretty common for both chemo regimens), topotecan was associated with a greater need for transfusions of both red cells (26% vs. 10%) and platelets (26% vs. 7%).

The study also evaluated several measures of quality of life (QoL), looking at a range of cancer-related symptoms to see how they changed over time. As we tend to see with treatment of advanced lung cancer, symptoms get worse over time even with treatment, but for every factor that was measured, the taxotere arm did better, with a slower rate of worsening than with topotecan:

So at the end of the day, topotecan was fairly comparable, but it was actually a little inferior to taxotere in both survival and QoL measures from start to finish, and it was associated with a greater need for transfusions. People came out of the original ASCO presentation less than blown away, since there was really nothing to recommend it over taxotere. Meanwhile, alimta had been shown to have nearly identical activity to taxotere but with significantly fewer side effects in terms of dropping blood counts, becoming a widely favored alternative.

Based on the findings from this study, I would relegate topotecan to the lower part of the list of agents that would be worth using for previously treated patients with advanced NSCLC. With taxotere, alimta, and tarceva appearing to have quite comparable activity overall (although we still don't have the results of a head to head comparison of taxotere or alimta vs. tarceva, but that trial is being done), I think topotecan falls a little behind the rest. Nevertheless, it's in a class of drugs that is similar to irinotecan (camptosar) but different from the taxanes (taxol, taxotere) or alimta or gemcitabine, so for the relatively uncommon patient who has already received the other options, it offers an altenative that is commercially available and actually has some evidence to show it belongs on the short list of drugs with established activity in patients who have already received chemo for advanced NSCLC.