Phase I study of 5-fluorouracil, leucovorin and bevacizumab in combination with radiation therapy in patients with locally advanced rectal cancer

Abstract

Abstract.A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of the standard treatment of 5-fluorouracil/l-leucovorin (5-FU/LV) with bevacizumab, in combination with radiation therapy in patients with locally advanced rectal cancer. Eligible patients had previously untreated stage T3 or T4 locally advanced rectal cancer. Patients received radiotherapy to the pelvis, at a total dose of 45 Gy in 25 fractions. During radiotherapy, patients received three courses of a simplified LV and 5-FU regimen (sLV5FU2), in combination with bevacizumab. Bevacizumab was infused at a fixed dose of 5 mg/ kg on Days 1, 15 and 29. The sLV5FU2 regimen consisted of 200 mg/m 2 of LV administered by continuous intravenous (i.v.) infusion over 2 h, followed by 400 mg̸m 2 of 5-FU administered by i.v. bolus injection, delivered at an initial loading dose of 2,000 mg/m 2 over 46 h. The dose was gradually increased to determine the MTD and RD of this regimen. Of the patients enrolled in the study, two developed Grade 3 diarrhea and one developed Grade 3 neutropenia. Since dose-limiting toxicity (DLT) occurred in two out of the six patients, 5-FU at a dose of 2,000 mg/m 2 over 46 h was determined as the MTD and designated as the RD, taking into consideration the toxicities in matched patients who received standard preoperative chemoradiotherapy with sLV5FU2 during the same period. The combination of 5-FU, LV, bevacizumab and radiotherapy in patients with locally advanced rectal cancer was found to be tolerable, with encouraging response rates. Further investigation is required in a phase II setting.

Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer

“…A CT-based treatment planning system was mandatory for defining the planning target volume, including the primary tumor, the surrounding mesorectum and bilateral LPLN, including the internal iliac, obturator, external iliac and common iliac areas, according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) classification (11). All the patients underwent concurrent 5-fluorouracil (5-FU)-based chemotherapy, including 5-FU̸leucovorin, tegafur̸uracil and S-1 (12,13). Long-course CRT was mainly used for patients with low-lying tumors and intended sphincter preservation, or tumors close to the circumferential margin.…”

Identification of Predictors of Recurrence in Patients with Lower Rectal Cancer Undergoing Neoadjuvant Chemotherapy: A Direct Comparison of Short-Course and Long-Course Chemoradiotherapy

“…All patients underwent concurrent 5-FU-based chemotherapy, including 5-FU/leucovorin, tegafur/uracil and S-1 [15,16]. A computed tomography (CT)-based treatment planning system was mandatory for defining the planning target volume, including the primary tumor, the internal iliac, obturator, external iliac and common iliac areas, according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) classification [17].…”