FOLFOX plus radiotherapy lowers adverse events in esophageal cancer
MedWire News: American Society of Clinical Oncology (ASCO) Annual Meeting; Chicago, IL, USA: 1-5 June, 2012. When added to radiotherapy, the combination chemotherapy - leucovorin, fluorouracil (5-FU), and oxaliplatin - known as FOLFOX offers an improved adverse event profile for esophageal cancer patients when compared with a 5-FU, cisplatin regimen, study findings show.
No improvement in efficacy was seen with the FOLFOX regimen over the cisplatin regimen, noted Thierry Conroy (Centre Alexis Vautrin, Vandoeuvre-lès-Nancy, France), who presented the results on the first day of the ASCO Annual Meeting.
The phase II/III PRODIGE 5/ACCORD 17 trial cohort comprised 267 previously untreated esophageal cancer patients who were unfit for surgery or had locally advanced tumors. Patients with metastases or multiple esophageal carcinomas were excluded from the study.
All the patients received 50 Gy (2Gy/fr) radiotherapy five days a week for 5 weeks. In addition, half the patients (arm A) were randomly assigned to receive six cycles of FOLFOX (oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, and a 5-FU 400 mg/m2 bolus on day 1 then 1,600 mg/m2 in 46 hour continuous infusion [ci]), three cycles of which were administered during radiotherapy and three after. The other half of the patients (arm B) received four cycles of cisplatin (75 mg/m2 day 1) and 5FU (1,000 mg/m2 per day, ci days 1-4), two cycles during and two after radiotherapy.
After a median follow up of 25.3 months, progression free survival and overall survival were similar in both arms A and B, at 9.7 months versus 9.4 months and 20.2 months versus 17.5 months, respectively. Primary toxicities were also similar, with no significant difference in hematologic adverse event rates between the two treatment groups.
Patients on the FOLFOX regimen had a better side-effect profile compared with those on the cisplatin regimen with significantly reduced rates of mucositis (26.7% vs 32.0%), alopecia (1.5% vs 9.4%), and elevated creatinine (3.0% vs 11.7%), although grades 1 and 2 neuropathy occurred more often in patients who were given FOLFOX than in those given cisplatin (18.3% vs 0.8%).
Most notably, patients in arm A had a significantly lower rate of death owing to toxicity or within 15 days of chemotherapy than those in arm B, at 1.1% versus 6.4% and 1.1% versus 3.2%, respectively.
"Concomitant chemoradiation with FOLFOX is a safer new option, especially in patients with contraindications to cisplatin," concluded Conroy. He added that FOLFOX is also more convenient and can be administered over a shorter time period than 5-FU/cisplatin (12 days vs 16-20 days).
Discussant for the study, Theodore Hong (Harvard Medical School, Boston, MA, USA) said that the significant difference in early death rates between the two regimens should encourage researchers to question the use of 5-FU/cisplatin in combination with radiotherapy for esophageal cancer patients. He suggested that early, unpredictable deaths due to frequent use of this regimen may have "confounded survival outcomes in multiple trials."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
By Helen Albert