Mitomycin and 5‐fluorouracil for second‐line treatment of metastatic squamous cell carcinomas of the anal canal

Abstract

BackgroundMetastatic squamous cell carcinomas (SCC) of the anal canal are rare and there is no international consensus on their second‐line management. 5‐Fluorouracil (5‐FU) and mitomycin in combination with radiotherapy is the standard for locally advanced forms but its efficacy in metastatic stage has never been evaluated.Patients and methodsWe report a retrospective analysis of patients treated with 5‐FU and mitomycin from 2000 to 2017 in our institution for a metastatic SCC of the anal canal after failure of platinum‐based regimen. The main outcome was progression‐free survival (PFS) and the secondary outcomes were overall survival (OS), response rate, and toxicity.ResultsNineteen patients, 15 women and four men, with a median age of 57 years were identified (range, 40‐79 years). Patients received a median of three cycles (1‐7) of mitomycin 5‐FU. A dose reduction was necessary in six patients (31.6%), one patient had to discontinue treatment following toxicity and no death was due to treatment toxicity was reported. An objective response was observed in five patients (26.4%, 95% CI 6.6‐46.2) including one complete response, six patients (31.6%, 95% CI 10.7‐52.5) showed tumor stabilization. Median PFS and OS were 3 months [95% CI 1‐5] and 7 months [95% CI 2.2‐11.8]. Responder had a median duration of response of 4 months [95% CI 1.8‐6.1] and one patient had 23 months duration of response. No significant difference was noted for PFS and OS for patients previously treated with mitomycin and 5‐FU at a local stage.ConclusionMitomycin and 5‐FU regimen provides tumor control with acceptable tolerance. It is an option for patients with metastatic SCC of the anal canal after failure of platinum‐based chemotherapy. [Correction added on 9 October 2019, after first online publication: '5‐FU' was inadvertently removed from the Results and Conclusion and has now been added to the text.]

Nonplatinum‐based therapy with Paclitaxel and Capecitabine for advanced squamous cell carcinomas of the anal canal: A population‐based Danish anal cancer group study

“…A relatively recent study assessed the benefits of Mitomycin and 5‐FU after failure of Cisplatin and 5‐FU in 19 patients. Similar ranges were seen with an ORR of 26%, median PFS of 3 months, and OS of 7 months 21 …”

Hepatic metastasis of anal squamous cell carcinoma

“…Saint et al evaluated the combination of mitomycin C and 5-FU as second-line chemotherapy in 19 patients with metastatic anal SCC. There was an acceptable tumour control with balanced toxicities, but the median progressive free survival and overall survivals were only 3 and 7 months, respectively 7. In our case, the isolated liver lesion was not highly suspicious of a metastatic anal SCC, and hence preoperative chemotherapy was not administered.…”

“…Nevertheless, the first-line choice of chemotherapy regimen usually consists of cisplatin and 5-FU. There is a relatively high response rates (30%–75%) but the response duration is short (5.8–8 months) 7. There is no consensus on the second-line chemotherapy regimen.…”

Real Impact of Novel Immunotherapy Drugs in Cancer. The Experience of 10 Last Years

“…The anti-PD1 moAbs, Pembrolizumab and nivolumab, as well as, the PD-L1 moAb, durvalumab, have been studied in the metastatic disease showing promising results in terms of PFS and OS [ 13 ]. Specifically, according to the phase Ib KEYNOTE-028 study, pembrolizumab has been tested in PD-L1 positive patients achieving overall response rate (ORR) 17%, whereas its median PFS period was 3 months and its median OS was 9.3 months in comparison with an OS of 7 months when chemotherapy with mitomycin C and 5FU was tested as second line of treatment [95% CI 2.2–11.8] [ 14 , 15 ]. Diarrhea, fatigue and nausea were included in the most common treatment-related side effects [ 14 , 15 ].…”

“… An overview of the mPFS and mOS in the context of anal [ 15 ], breast [ 18 , 19 ], colorectal [ 21 ] and head and neck cancer [ 28 , 29 ]. mPFS, median progression-free survival, mOS, median overall survival.…”