The Annals of Oncology recently reported that weekly doses of the drugs oxaliplatin (Eloxatin®) and 5-FU given concurrently with radiation therapy shows promising activity for the treatment of locally advanced rectal cancer.
Rectal cancer is a disease in which malignant cells arise from the cells of the rectum. The rectum is part of the digestive system and comprises the final 6 inches of the large intestine. Current treatments for rectal cancer include surgery, chemotherapy and radiation. Some of the factors influencing the choice of treatment include the risk of recurrence, the extent of the cancer, the general health of the patient and whether or not the cancer has recurred after previous treatment. Locally advanced rectal cancer is deemed incurable by surgery alone. However, there has been progress in the administration of concurrent chemotherapy and radiation therapy prior to surgery to reduce the size of the cancer to make surgery feasible. The usual chemotherapy treatment is the combination of 5-FU and leucovorin. More recently Eloxatin® has emerged as an active agent for the treatment of colorectal cancers.
Eloxatin has been previously shown to increase the anti-tumor activity of the drug 5FU, as well as improving the patient’s sensitivity to radiation. This phase I-II study was designed to determine the dosages and tolerability of Eloxatin administered on a weekly basis along with daily radiation. Forty-six patients diagnosed with recurrent or locally advanced rectal cancer were treated with escalating doses of Eloxatin and a continuous infusion of 5FU for six weeks. They also received preoperative radiation therapy. The escalating doses of weekly doses of Eloxatin were 25, 35, 45 and 60 mg/m2.
During the escalating phase of treatment, dose-limiting side effects occurred infrequently and primarily consisted of diarrhea. At the study’s completion, the recommended dosage of Eloxatin was 60 mg/m2 and 5FU 225mg/m2/day. Among the 25 patients who reached these doses during the treatment period, 16 percent developed moderate diarrhea and 12 percent developed mild neuropathy. All of the patients completed radiation and were operated on as scheduled. Restaging after chemotherapy and radiatiaon therapy and radiation therapy showed downstaging in 21 of the 25 patients. Seven (28 percent) of the patients achieved a complete pathological response, while 12 (48 percent) had residual tumors that had been markedly reduced by the chemotherapy with none having nodal involvement.
Researchers were encourage by the findings of this early study, which indicated that rectal tumors can be effectively treated and down staged with the combination of weekly Eloxatin, continuous 5FU and concomitant radiation. Given the low toxicity rates and the promising response rates, this regimen will be compared to other standard 5FU-based chemotherapy/radiation regimens in the future.
Reference: Aschele C, Friso M, Pucciarelli S, et al. A Phase I-II Study of Weekly Oxaliplatin, 5-Fluorouracil Continuous Infusion and Preoperative Radiotherapy in Locally Advanced Rectal Cancer. Annals of Oncology. 2005;16: 1140-1146.