FLOT: An Effective Regimen for Gastric or Gastro-esophageal Cancer
FLOT: An Effective Regimen for Gastric or Gastro-esophageal Cancer
Abstract & Commentary
By William B. Ershler, MD
Synopsis: A new regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT]) was tested in a phase II trial in 54 patients with gastric or gastro-esophageal cancer. Response rates were comparable, or perhaps even a little better than those published for other combinations; the toxicity profile appears favorable.
Source: Al-Batran SE, et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008;19:1882-1887.
Systemic chemotherapy offers palliation and improved overall survival for patients with advanced gastric cancer.1 Fluorouracil (FU) and cisplatin are commonly employed alone or in combination. Recently, a phase III trial demonstrated the addition of docetaxel to cisplatin and FU (DCF) was superior to cisplatin and FU (CF) in terms of quality of life, response rate, time to progression, and overall survival.2 Despite the improvements observed, enthusiasm for this combination is tempered by the high level of toxicity observed, including grade 3/4 neutropenia, which occurred in more than 80% of those on the phase III trial, and substantial other toxicities, including stomatitis (21%), diarrhea (19%) and vomiting (14%). In recognition of this, other combinations, including docetaxel, have been tested. The current study was designed to incorporate docetaxel into a tolerable bi-weekly, oxaliplatin-based chemotherapy regimen.
Patients with measurable, metastatic adenocarcinoma of the stomach or esophagogastric junction and no prior chemotherapy received oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2 as a 24-hour infusion in combination with docetaxel 50 mg/m2 (FLOT) on day 1 every two weeks. Prophylactic growth factors were not administered.
Fifty-nine patients were enrolled; 54 received treatment. Patients had a median age of 60 years (range 29-76), and most (93%) had metastatic disease. Objective responses were observed in 57.7% of patients with a median time-to-treatment response of 1.54 months. Median progression-free survival (PFS) and overall survival were 5.2 and 11.1 months, respectively. Twenty-five percent of patients experienced prolonged (> 12 months) PFS. Frequent (> 10%) grade 3 or 4 toxic effects included neutropenia in 26 (48.1%), leucopenia in 15 (27.8%), diarrhea in 8 (14.8%), and fatigue in 6 (11.1%) patients. Complicated neutropenia was observed in two (3.8%) patients only.
Commentary
Compared to earlier regimens, the results established by the V-325 trial for the DCF regimen set a high bar for response rates in the treatment of gastric carcinoma.2 Acknowledging the risks of interstudy comparison, it's difficult to resist contrasting the FLOT response rate of 57.7%, PFS of 5.2 months, one-year survival rate of 42%, and OS of 11.1 months with those same parameters achieved with DCF (response rate 37%, PFS 5.6 months; OS 9.6 months; one-year survival rate of 40%). But what is more impressive is the lower rate of both hematological and non-hematological toxicity. Adverse reactions included what might be expected from these drugs (docetaxel, FU, and oxaliplatin), and included grade 3 or 4 neutropenia in 48% of those treated. However, only two patients experienced "complicated" neutropenia, and again, this contrasts favorably when compared with DCF (grade 3 or 4 neutropenia, 82%; "complicated" neutropenia, 29%). FLOT was also associated with lower rates of non-hematological toxicity (diarrhea in 15% and neuropathy in 9%).
It might be premature to adapt FLOT as primary therapy for those with gastric or gastro-esophageal cancer, but certainly this combination deserves additional study. A phase III trial comparing the two regimens (FLOT vs DCF) would be a logical next step.
References
1. Khushalani N. Cancer of the esophagus and stomach. Mayo Clin Proc. 2008;83:712-722.
2. Ajani JA, et al. Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: The V-325 Study Group. J Clin Oncol. 2007;25: 3205-3209.
A new regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT]) was tested in a phase II trial in 54 patients with gastric or gastro-esophageal cancer. Response rates were comparable, or perhaps even a little better than those published for other combinations; the toxicity profile appears favorable.Subscribe Now for Access
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