First-Line Modified DCF Regimen Trialled For Advanced Anal Squamous Cell Carcinoma

A modified version of docetaxel, cisplatin and fluorouracil may be feasible for the treatment of metastatic or inoperable recurrent anal squamous cell carcinoma

medwireNews: A modified first-line regimen of docetaxel, cisplatin and fluorouracil (DCF) may reduce toxicity compared with the standard protocol, while achieving a comparable rate of complete response and long-term remission for patients with advanced anal squamous cell carcinoma, suggest results from a phase II trial. 

The Epitopes-HPV02 study included 66 patients with previously untreated metastatic or unresectable recurrence and an ECOG performance status of 0 or 1, explain Stefano Kim, from the University Hospital of Besançon in France, and co-workers. 

Patients who were aged 75 years or younger and who had an ECOG performance status of 0 were recommended to receive six 21-day cycles of a standard DCF regimen, consisting of cisplatin 75 mg/m2 plus docetaxel 75 mg/m2 on day 1 and fluorouracil 750 mg/m2 for 5 days.  

Older patients and those with an ECOG score of 1 were instead recommended for eight cycles of a modified regimen of docetaxel 40 mg/m2 and cisplatin 40 mg/m2 given on day 1 and fluorouracil 1200 mg/m2 for 2 days every 2 weeks, the investigators explain. 

The primary endpoint of a 1-year progression-free survival (PFS) rate of 17% in the first 21 evaluable patients was exceeded, with 48% of these individuals alive and disease-free at this time, the researchers report in The Lancet Oncology

And at final analysis, after a median of 19.8 months, 1-year PFS was achieved by 61% of the 36 patients using the standard regimen and 60% of the 30 patients who received the modified protocol. An objective response was achieved in 89% and 83%, respectively, including complete responses in 42% and 47%. 

Safety analysis showed that dose reductions were required by 75% of patients using standard DCF versus 50% of those given the modified regimen, with a median of 6.0 and 7.5 cycles of treatment administered, respectively. 

Grade 3–4 adverse events in the standard and modified DCF groups included neutropenia (22 vs 23%), diarrhoea (25 vs 10%), asthenia (22 vs 7%), anaemia (17 vs 13%), lymphopenia (8 vs 17%), mucositis (19 vs 0%) and vomiting (14 vs 7%).  

Of note, non-haematological grade 4 adverse events occurred in 8% of patients using standard DCF and 14% experienced febrile neutropenia, whereas neither of these occurred among the modified DCF patients; 69 serious adverse events occurred in the standard DCF groups versus 28 in those using the modified regimen. 

Stefano Kim et al suggest that the first-line modified DCF regimen “could be considered as a new standard of care” in patients with metastatic or unresectable locally recurrent disease. 

“Regarding the elevated risk of high-grade and serious adverse events and febrile neutropenia, standard DCF cannot be recommended in this situation,” they believe. 

Writing in an accompanying comment, Francesco Sclafani, from The Royal Marsden NHS Foundation Trust in Sutton, UK, agrees that the study has “favourable outcome data compared with previous historical treatments”. 

However, he cautions that the Epitopes-HPV02 trial “does not answer the question of whether adding docetaxel to cisplatin and fluorouracil provides a significant and clinically meaningful incremental survival advantage without increasing the number of adverse events or compromising quality of life.” 

The improvement with triplet chemotherapy versus earlier trials of doublet regimens “might at least partly reflect differences in quality and heterogeneity between studies”, the commentator says and he therefore recommends that a sequential first-line approach of platinum plus fluoropyrimidine followed by taxane chemotherapy on progression “should still be considered an acceptable approach, especially for patients who are less fit or when adverse events are a concern.” 



Kim S, François E, André T, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre , single-arm, phase 2 study . Lancet Oncol; Advance online publication 2 July 2018.

Sclafani F. Building evidence-based treatment recommendations for advanced anal cancer: the time is now . Lancet Oncol; Advance online publication 2 July 2018.

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