Managing FLOT Toxicity With Dose Reductions in Gastroesophageal Cancer

In an interview with CancerNetwork®, Rutika Mehta, MD, MPH, director of Upper Gastrointestinal (GI) Medical Oncology at NYU Langone Health’s Perlmutter Cancer Center, discussed her framework for dosing and dose modifications with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) in patients with gastroesophageal cancer.

Mehta explained that for elderly or frail patients who remain surgical candidates, she may prefer a doublet such as FOLFOX (leucovorin, fluorouracil, and oxaliplatin), whereas younger candidates start FLOT with preemptive growth factor support during the first cycle. When toxicities such as neuropathy arise, she favors a global dose reduction of oxaliplatin and docetaxel to preserve the benefit of a triplet regimen, dropping a single agent only for agent-specific toxicities such as refractory edema with docetaxel or an infusion reaction to oxaliplatin. When moving to 2 agents, she extends the continuous 5-fluorouracil infusion from 24 to 46 hours.

Transcript:

Mehta: FLOT dosing has been a constant challenge for my elderly, frail patients. If they’re still surgical candidates, I prefer doing a doublet like FOLFOX, although it’s not ideal. In my otherwise young patients who are candidates for surgery, I start with FLOT, and I preemptively give them growth factor support with the first treatment because I know that their counts will drop. Then I learn how their counts recover with the second cycle, and that helps me decide if I need to give it every time or every other time.

When toxicities start, typically neuropathy, I try to do a global dose reduction of both oxaliplatin and docetaxel together. I try not to drop one agent completely, because I still want to give them some benefit of a triplet regimen. If they’re having [adverse] effects that are more significant with one or the other, like docetaxel causing significant edema that I’m not able to resolve with steroids, then of course I’ll have to drop that. Or if they had an infusion reaction to oxaliplatin, then I would drop oxaliplatin altogether. If I do that, I also tend to increase the 5-fluorouracil continuous pump from 24 hours to 46 hours when I’m giving just 2 agents, as we do with FOLFOX.