We've always been tempted to see if we can add more to standard approaches to improve our outcomes. In SCLC, people have attempted to add taxol to cisplatin and etoposide as part of the PET regimen (platinum + etoposide + taxol). Although heavily tested, it clarified that triplet therapy with standard chemo for SCLC appears to be associated with no improvement in outcomes but with a very significant improvement in side effects, including risk of dying from treatment.
In the late 1990s, when taxol was still one of the newer drugs for lung cancer, several groups, including SWOG, CALGB, and a Greek lung cancer group ran small clinical trials that looked promising for a few dozen trials. However, the Greak Lung Cancer Cooperative Group reported results of a randomized trial that closed early, comparing cisplatin/etoposide to the triplet that added taxol, having included 133 patients with either LD-SCLC or ED-SCLC (paper here):
(Click on image to enlarge)
Despite giving G-CSF (white blood cell growth factor) support in order to reduce potential toxicity, the study showed that patients getting the triplet didn't do any better and had far worse drops in blood counts and a significant increase in deaths due to treatment:
(neutropenia is low white cells, and thrombocytopenia is low platelets).
But this wasn't a huge trial, and perhaps the PET triplet looked bad for this one study.
Unfortunately, it didn't fare any better in a trial across North America (an Inter-group trial including the various cancer cooperative study groups)(abstract here). This was much larger and had the same basic design of standard doublet platinum-etoposide vs. PET triplet, and it included nearly 600 patients with ED-SCLC:
As with the Greek trial, the triplet was associated with essentially identical activity, but the rate of dying from treatment was more than doublet with the triplet (and the WBC growth factor protected people with the PET triplet from low WBCs but not low platelets).
These two studies have pretty much clarified that the PET triplet is dangerous and doesn't add anything, and I suspect we'd find similar results with other triplets with standard chemo. As noted in a prior post, doublet chemo with a targeted agent like avastin is feasible, but it's not clear that it really adds anything either. Platinum and etoposide may be the same regimen we've been using for more than a decade, but only because it has withstood the test of time and many challengers thus far.
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