Two Case Reports of Resensitization to Previous Chemotherapy with the Novel Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic Colorectal Cancer Patients
A 62-year-old man with a chief complaint of hematochezia was diagnosed with KRAS wild-type cancer of the sigmoid colon in 2007. The patient was initially treated with FOLFIRI+bevacizumab, and when the disease progressed, he received several therapies both alone and in combination: cetuximab, bevacizumab, capecitabine, gemcitabine, oxaliplatin, axitinib and irinotecan. On enrollment in the phase-1 study of the experimental drug RRx-001, a computed tomography (CT) scan revealed multiple metastases in the liver, bone and lungs. The patient received RRx-001 at a dose of 10 mg/m2 weekly over a period of approximately 9 months, receiving a total of 39 doses. RRx-001 was well tolerated, with the only treatment-related toxicity being pain on infusion that was readily managed. During this time, the patient had stabilization of his disease and was essentially asymptomatic. In addition, his ECOG performance status improved from 1 to 0, and he not only returned to full-time employment but also began to exercise vigorously.\nAfter nearly 10 months of treatment with RRx-001, he had progressive disease with elevation of the carcinoembryonic antigen (CEA) and increased tumor size, and was therefore discontinued from the trial. During the 2-week period between discontinuation of RRx-001 and resumption of a new therapy, there was a rapid increase in the slope of his CEA levels, suggesting that RRx-001 had suppressed tumor growth even after he met the criteria for progression.\nThe principal investigator (T.R.) restarted FOLFIRI, and the patient was treated for approximately 5 months, resulting in a sharp decline in the CEA levels from 511 to 162 (fig. ). After 5 months of therapy, a rise in CEA (table ) and a CT scan confirmed progression, and the treatment regimen was discontinued.