Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
Tóm tắt
PURPOSE: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point.
PATIENTS AND METHODS: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m2/d) followed by a 5FU bolus (400 mg/m2/d) and 22-hour infusion (600 mg/m2/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m2 as a 2-hour infusion on day 1.
RESULTS: Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 v 6.2 months; P = .0003) and better response rate (50.7% v 22.3%; P = .0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 v 14.7 months; P = .12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (41.7% v 5.3% of patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity (18.2% v 0%), but this did not result in impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment (P = .004).
CONCLUSION: The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.
Từ khóa
Tài liệu tham khảo
Levi F, Perpoint B, Garufi C, et al: Oxaliplatin activity against metastatic colorectal cancer: A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate. Eur J Cancer 29A:1280,1993–1284,
Diaz-Rubio E, Sastre J, Zaniboni A, et al: Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: A phase II multicentric study. Ann Oncol 9:105,1998–108,
Becouarn Y, Ychou M, Ducreux M, et al: A phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. J Clin Oncol 8:2739,1998–2744,
Mantel N, Haenzel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719,1959–748,
Cox J, Pazdur R, Thibault A, et al: A phase III trial of Xeloda (capecitabine) in previously untreated advanced/metastatic colorectal cancer. Proc Am Soc Clin Oncol 18:265a,1999 (abstr 1016)
Twelves C, Harper P, Van Custem E, et al: A phase III trial of Xeloda (capecitabine) in previously untreated advanced/metastatic colorectal cancer. Proc Am Soc Clin Oncol 18:263a,1999 (abstr 1010)
Pazdur R, Douillard JY, Skillings JR, et al: Multicenter phase III study of 5-fluorouracil (5-FU) or UFT in combination with leucovorin (LV) in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 18:263a,1999 (abstr 1009)
Carmichael J, Popiela T, Radstone D, et al: Randomized comparative study of Orzel (oral uracil/tegafur (UFT) plus leucovorin (LV)) versus parenteral 5-fluorouracil (5-FY) plus LV in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 18:264a,1999 (abstr 1015)
Punt CJA, Keizer HJ, Douma J, et al: Multicenter randomized trial of 5-fluorouracil (5FU) and leucovorin (LV) with or without trimetrexate (TMTX) as first line treatment in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol 18:262a,1999 (abstr 1006)
Saltz LB, Locker PK, Pirotta N, et al: Weekly irinotecan, leucovorin and fluorouracil is superior to dailyx5 LV/FU in patients with prviously untreated metastatic colorectal cancer. Proc Am Soc Clin Oncol 18:233a,1999 (abstr 898)
Tournigand C, de Gramont A, Louvet C, et al: A simplified bimonthly regimen with leucovorin and 5-fluorouracil for metastatic colorectal cancer. Proc Am Soc Clin Oncol 17:274,1998 (abstr 1052)