Stefano Kim, MD
In a French phase II trial reported in The Lancet Oncology, Stefano Kim, MD, of the Department of Oncology, University Hospital of Besancon, and colleagues found that treatment with docetaxel, cisplatin, and fluorouracil (DCF) was active in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma.
The multicenter study included 66 evaluable chemotherapy-naive patients enrolled between September 2014 and December 2016 who received either six cycles of standard DCF (n = 36; docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1 and fluorouracil 750 mg/m2 per day for 5 days every 3 weeks) or eight cycles of modified DCF (n = 30; docetaxel 40 mg/m2 and cisplatin 40 mg/ m2 on day 1 and fluorouracil 1,200 mg/m2 per day for 2 days every 2 weeks). The choice between standard or modified DCF was based on patient clinical status or investigator choice. Standard DCF was recommended for patients aged ≤ 75 years and with Eastern Cooperative Oncology Group (ECOG) performance status of 0, and modified DCF was recommended for those older than 75 years or with ECOG performance status of 1.
The primary endpoint was investigator-assessed progression-free survival at 12 months; for the primary endpoint to be met, ≥ 11 (≥ 17%) of the 66 patients had to be alive without disease progression at 12 months.
Overall, 31 (47%) of 66 patients were alive and progression-free at 12 months. Median follow-up among all patients was 19.8 months. Median progression-free survival was 11.0 months among all patients, 10.7 months in the standard DCF group, and 11.0 months in the modified DCF group. On investigator assessment, objective response was observed in 86% of all patients (including complete response in 44%), 89% of the standard DCF group (complete response in 42%), and 83% of the modified DCF group (complete response in 47%).
Grade 3 or 4 adverse events occurred in 70% of patients, including 83% of the standard DCF group and 53% of the modified DCF group. The most common grade 3 or 4 adverse events were neutropenia (23%; 22% in the standard DCF group vs 23% in the modified DCF group), diarrhea (18%; 25% vs 10%), asthenia (15%; 22% vs 7%), anemia (15%; 17% vs 13%), lymphopenia (12%; 8% vs 17%), mucositis (11%; 19% vs 0%), and vomiting (11%; 14% vs 7%). No grade 4 nonhematologic adverse events or febrile neutropenia occurred with modified DCF, whereas grade 4 nonhematologic adverse events occurred in 3 patients (8%) and febrile neutropenia in 5 patients (14%) in the standard DCF group. A total of 69 serious adverse events occurred in the standard DCF group vs 28 in the modified DCF group. No treatment-related deaths were reported.
The investigators concluded, “Compared with standard DCF, modified DCF provided long-lasting response with good tolerability in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma with ECOG performance status of 0–1 in the first-line setting…. Regarding the elevated risk of high-grade and serious adverse events and febrile neutropenia, standard DCF cannot be recommended in this situation.” ■