PURPOSE: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. METHODS AND MATERIALS: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). RESULTS: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). CONCLUSIONS: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.