The fact is that lung cancer, like many others, is a disease disproportionately affecting older populations, with the median age now in the 69-70 range.
But our trials in lung cancer only rarely involve patients over 70. This leaves us with serious questions about the best way to treat older and poor performance status patients. It's also important to note that elderly doesn't mean poor performance status. There are remarkably healthy older patients, now more than ever, and there are also debilitated patients under 70 as well:
But a lot of patients with SCLC are elderly and/or frail when they present for treatment, and the question is whether they should be treated the same as younger patients or whether plans should be modified.
Some oncologists feel that the detrimental effects of chemotherapy exceed the anticipated benefit of it in elderly or debilitated patients. There are, however, a couple of retrospective studies that suggest that older patients can benefit from treatment. Dr. Frances Shepherd reviewed results from 123 patients with SCLC, either LD- or ED-SCLC, who were 70 or older (abstract here). In fact, 14 of the 123 were 80 or older and 80% had other illnesses. Two thirds were treated with combination chemo, 16% with radiation alone, and 20% received only supportive care, a few due to their refusal of treatment but the majority by treating physician recommendation. Survival was highly correlated with the degree of treatment they received: median survival was 10.7 months for patients who received 4-6 cycles of chemo (3.9 months if 3 or less), 7.8 months for those who received radiation alone, and just 1.1 months for those who received supportive care only. While these results suggest that patients can have improved survival with chemo, the patients who were recommended to receive supportive care were overall a frail lot, much more than the group who were recommended to receive treatment (performance status 3 or 4 in 62% on supportive care vs. 34% of patients on chemo). It's a retrospective analysis, so it's not clear if they did poorly because they were denied chemo or they were denied chemo because they were really so weak they were going to do very poorly no matter what and were recommended to not pursue aggressive therapy.
Other retrospective studies have shown similar results. In one (abstract here), 312 patients with SCLC who , including 81 age 70 or older, were compared in terms of results by age, including 60 or younger and 61-69. Only 10% of the youngest group had a performance status of 3 or 4 that would be considered quite debilitated, vs. 22% of the 70 and over age group. In addition, the older patients were far mroe likely to have other major medical problems than the young patients (75% vs. 48%). Despite older patients receiving fewer cycles of chemo and having more dose reductions, there were essentially comparable response rates as well as median and long-term survival numbers compared to younger patients with SCLC. Again, however, a retrospective study may not be easily generalizable to everyone, because the people who were recommended to have chemo may have been different from the ones who were recommended to not pursue it.
There have also been a couple of trials that tested deliberately lighter, potentially kinder and gentler chemo vs. more standard treatment. Etoposide is one of the most commonly used chemo agents for SCLC and is available in an oral form. One was performed in the UK by Girling and colleagues from the Medical Research Council Lung Cancer Working Party (abstract here), in which 339 patients with marginal to poor performance status (2-4) who were not previously treated for ED-SCLC were randomized to receive oral single-agent etoposide or combination IV chemo:
The trial was actually originally designed to enroll 450 patients but stopped early, when an interim analysis showed a significant survival advantage for the recipients of combination chemo (median survival 6.0 vs. 4.3 months, p = 0.03):
In fact, a very similar trial by Souhami and colleagues (abstract here) out of London was very similar, albeit smaller. In that trial, 155 patients with ED-SCLC were randomized to receive oral etoposide alone or alternating platinum/etoposide or CAV (an older IV chemo regimen for SCLC) for up to six cycles. Again the trial was stopped early, when an interim analysis showed that patients receiving the more aggressive IV chemo combination had a better median (5.9 vs. 4.8 month) and one year survival (19% vs. 10%; p = 0.05).
Overall, then, while the elderly and poor performance status population is still understudied, considering how common such patients really are in the real world, the available data really suggest that for a relatively chemo-responsive cancer like SCLC, giving as aggressive of a treatment as patients can manage appears to be worthwhile, translating to better survival that may be comparable to younger, healthier patients.
ONKTALK is tomorrow.
I hope to see you there.
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