Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection.

Author(s): Hildebrandt B, Rau B, Loffel J, Wust P, Nicolaou A, Gellermann J, Le Coutre P, Neuhaus P, Felix R, Wernecke KD, Dorken B, Riess H

Affiliation(s): Medizinische Klinik fur Hamatologie und Onkologie, Charite, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. bert.hildebrandt@charite.de

Publication date & source: 2006-09, Int J Colorectal Dis., 21(6):582-9. Epub 2006 Jan 14.

Publication type: Clinical Trial, Phase III; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND AND AIMS: The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated. PATIENTS AND METHODS: We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups. RESULTS: Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group. INTERPRETATION/CONCLUSION: Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.