Kim S, et al. - Researchers intended to verify if docetaxel, cisplatin, and fluorouracil (DCF) chemotherapy shows clinical activity and is safe in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma. With good tolerability, modified DCF offered long-lasting response vs standard DCF in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 in the first-line setting. Hence, modified DCF could be considered as a new standard of care for these patients. No recommendation was made for standard DCF in this situation due to the elevated risk of high-grade and serious adverse events and febrile neutropenia.

Methods

• In this multicenter, single-arm, phase 2 study, researchers included patients from 25 academic hospitals, cancer research centers, and community hospitals in France who were aged 18 years or older with histologically confirmed anal squamous cell carcinoma with metastatic disease or with unresectable local recurrence, an ECOG performance status of 0 or 1, and with at least one evaluable lesion according to the Response Evaluation Criteria in Solid Tumors (version 1.1).
• They assigned chemotherapy-naive patients to receive either six cycles of standard DCF (75 mg/m²docetaxel and 75 mg/m² cisplatin on day 1 and 750 mg/m² per day of fluorouracil for 5 days, every 3 weeks) or eight cycles of modified DCF (40 mg/m² docetaxel and 40 mg/m² cisplatin on day 1 and 1200 mg/m² per day of fluorouracil for 2 days, every 2 weeks), administered intravenously.
• Recommendation for the standard vs modified regimens was based on, but not limited to, age (≤ 75 years vs > 75 years) and ECOG performance status (0 vs 1).
• Investigator-assessed progression-free survival at 12 months from the first DCF cycle was primary endpoint; at least 11 (17%) of 66 enrolled patients had to be alive without disease progression at 12 months to meet the primary endpoint.
• Using a modified intention-to-treat population, defined as all patients who were evaluable for progression at 12 months who received at least one cycle of DCF, they performed efficacy and safety analyses.

Results

• A total of 69 patients were enrolled between Sept 17, 2014 and Dec 7, 2016; DCF was not received by three of these patients, while the standard DCF regimen was received by 36 and modified DCF by 30 of the remaining 66 patients.
• Since 31 (47%) of 66 patients were alive and progression free at 12 months, the primary endpoint was met.
• Disease progression at data cutoff was reported in 22 (61%) of 36 patients who received the standard DCF regimen and 18 (60%) of 30 patients who received the modified DCF regimen.
• They found at least one grade 3-4 adverse event in 46 (70%) of 66 patients (30 [83%] of 36 receiving the standard DCF regimen and 16 [53%] of 30 receiving the modified DCF regimen).
• Neutropenia (15 [23%]; eight [22%] for standard DCF vs seven [23%] for modified DCF), diarrhea (12 [18%]; nine [25%] vs three [10%]), asthenia (ten [15%]; eight [22%] vstwo [7%]), anemia (ten [15%]; six [17%] vs four [13%]), lymphopenia (eight [12%]; three [8%] vs five [17%]), mucositis (seven [11%]; seven [19%] vs none), and vomiting (seven [11%]; five [14%] vs two [7%]) constituted the most common grade 3-4 adverse events.
• Modified DCF resulted in no grade 4 non-hematological adverse events or febrile neutropenia, while treatment with standard DCF resulted in three (8%) grade 4 non-hematological adverse events and five (14%) cases of febrile neutropenia.
• They reported 97 serious adverse events (69 in patients who received the standard DCF regimen [61 drug-related] and 28 in those given the modified DCF regimen [14 drug-related]).
• Data showed no treatment-related deaths.