Background: Anal cancer (AC) is a relatively uncommon malignancy in the United States, however, this disease continues to increase in incidence, especially in individuals over 50 years old. Current standard of care for locoregional disease includes mitomycin and 5-fluorouracil (M/5FU) with radiation. This combination is associated with significant toxicity limiting its use in those patients who are elderly or have multiple comorbidities. Carboplatin and paclitaxel (C/P) is now the preferred standard of care treatment regimen for metastatic AC. Weekly C/P has become a standard of care option in combination with radiation for locally advanced esophageal cancer. Here we evaluate the efficacy of weekly C/P chemoradiation in treating a cohort of patients unable to receive standard M/5FU chemoradiation. Methods: Subjects were consented to an IRB approved AC registry at the University of Wisconsin Carbone Cancer Center. Patients (pts) were identified to have received weekly infusional C/P concurrent with standard-dose radiation for localized AC between January 1, 2016 and December 1, 2022. Clinical response was determined based on evidence of disease on imaging or anoscopy and toxicities were graded according to CTCAE v5. Results: 8 pts (7F/1M; median age 76 (54-87)) were found to meet eligibility criteria. 6 had perianal cancers and 2 had cancers within the anal canal. 6 had T2 disease and 2 had T3 tumors. 2 had node positive disease. Dosing ranged from C (AUC 1.5-2), P (30-50mg/m2) and radiation (50.4-58 Gy). Patients completed a median of 82.5% (40%-100%) of intended treatments. Most common toxicities included leukopenia, anemia, perianal pain, and fatigue. Grade 3 or higher toxicities included neutropenia (3) of which 2 resulted in febrile neutropenia, and anemia (3). All patients had a complete clinical response. With a median follow-up of 17 mos (3-40 mos), no patients have had recurrence and all patients are still alive. Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive M/5FU. This regimen merits further investigation in prospective clinical trials.