Squamous cell carcinoma represents approximately 75% of all anal cancers. Squamous cell carcinoma of the anal canal is a rare malignancy often curable in the early stages with the combined modality therapy of chemoradiation. Treatment in the metastatic setting is challenging due to the rarity of metastatic disease with the majority of patients presenting with curative locally advanced disease, and the ability to design clinical trials for metastatic disease has yet to be explored. There are no established chemotherapy guidelines for patients with metastatic anal cancer after the failure of cisplatin and fluorouracil. We used PubMed and OVID research engines to identify publications in English literature addressing treatments/therapeutics using the following keywords "metastatic anal cancer" and "metastatic squamous cell carcinoma of anus" in addition to reviewing related clinical trials in clinicaltrials.gov. We hereby report our experience in using aggressive combinations in the second- and third-line settings. A 49-year-old white male diagnosed with T3 N3 M0 Stage IIIB anal cancer was treated initially with surgical excision and adjuvant fluorouracil/cisplatin due unavailability of mitomycin. He developed metastatic disease to the skin and perianal region, was treated with four cycles of paclitaxel, ifosfamide, and cisplatin with growth factor support, and achieved minimal residual disease. On progression five months after finishing therapy, we treated him with mitomycin and cetuximab with mixed response after two cycles. The patient later elected to proceed with hospice care only and succumbed to his disease 16 months after first cycle of paclitaxel, ifosfamide, and cisplatin and 24 months from diagnosis. Paclitaxel, ifosfamide, and cisplatin is highly active in metastatic setting in selected patients. Cetuximab based regimen can be valuable option as second or third line. Paclitaxel, ifosfamide, and cisplatin and mitomycin and cetuximab can be available options for unmet need in metastatic anal cancer.
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