Phase I trial of oral topotecan (OT) and radiotherapy (XRT) in rectal cancer (RCA)

3743 Background: OT and XRT are synergistic in the laboratory. Methods: To define the MTD, DLT, and PKs (blood samples at time 0 - immediately after taking OT - and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, and 8 hrs after). The amount and subcellular location of DNA topoisomerase (topo) I and IIα - by intensity of fluorescence using monoclonal and polyclonal antibodies and gene expression by oligonucleotide microarray, were studied in RCA biopsies before and during (after 2 weeks) OT and XRT. Eligible pts had locally advanced, M0, RCA staged by EUS, CT scan +/- PET scan, good PS, and good organ function. OT escalated in cohorts of 3 to 6 pts taken at least 3 hrs prior to 1.8 Gy/fraction XRT to a total of 45Gy (standard pelvic fields), Monday through Friday. All post OT + XRT patients had curative, rectal-sparing surgery. 5-FU-based chemotherapy in the adjuvant setting was offered off protocol. Results: 13 patients enrolled (table). The median age was 69 years (range 38–90). M:F=11:2. ECOG PS: 0 (70%), 1 (30%)...