Randomized multicenter phase II trial of bolus plus infusional fluorouracil/leucovorin compared with fluorouracil/leucovorin plus oxaliplatin as third-line treatment of patients with advanced colorectal cancer Journal Article
| Authors: | Kemeny, N.; Garay, C. A.; Gurtler, J.; Hochster, H.; Kennedy, P.; Benson, A.; Brandt, D. S.; Polikoff, J.; Wertheim, M.; Shumaker, G.; Hallman, D.; Burger, B.; Gupta, S. |
| Article Title: | Randomized multicenter phase II trial of bolus plus infusional fluorouracil/leucovorin compared with fluorouracil/leucovorin plus oxaliplatin as third-line treatment of patients with advanced colorectal cancer |
| Abstract: | PURPOSE: The addition of oxaliplatin to fluorouracil (FU) and leucovorin (LV) improves the outcome of patients with colorectal cancer (CRC). This multicenter study evaluated FU/LV with or without oxaliplatin in patients with metastatic CRC after disease progression on sequential fluoropyrimidine and irinotecan. PATIENTS AND METHODS: Two hundred fourteen patients were randomly assigned to receive LV 200 mg/m2 intravenously (IV) and FU 400 mg/m2 IV bolus, followed by FU 600 mg/m2 IV over 22 hours on days 1 and 2, every 2 weeks (LV5FU2); or LV and FU as described, plus oxaliplatin 85 mg/m2 IV over 2 hours on day 1 of the schedule (FOLFOX4). The primary end point was overall response. RESULTS: Baseline characteristics were similar in the two treatment arms. Objective response (complete + partial) rates for LV5FU2 versus FOLFOX4 were 2% v 13% (P = .0027), respectively. Median time to disease progression was 2.4 v 4.8 months (P < .0001), and median survival was 11.4 v 9.9 months (P = .20) for LV5FU2 and FOLFOX4, respectively. Among the 72 patients who crossed over from LV5FU2 to FOLFOX4, 6% responded. Symptomatic improvement was significantly better for patients in the FOLFOX4 arm (32% v 18% for LV5FU2, P = .05). Grade 3/4 toxicities for LV5FU2 and FOLFOX4 were neutropenia (13% and 42%, respectively), diarrhea (6% and 16%, respectively), and overall neuropathy (0% and 6%, respectively). CONCLUSION: In patients with metastatic CRC, the FOLFOX4 regimen was superior to LV5FU2 with a higher response rate and time to disease progression. FOLFOX4 is an effective regimen even after disease progression on two previous chemotherapy regimens with fluoropyrimidines and irinotecan. |
| Keywords: | survival; adult; controlled study; treatment outcome; aged; disease-free survival; middle aged; survival analysis; clinical trial; mortality; fluorouracil; dose response; comparative study; disease free survival; cancer staging; antineoplastic agent; neoplasm staging; adenocarcinoma; controlled clinical trial; phase 2 clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; drug administration schedule; pathology; dose-response relationship, drug; risk assessment; colorectal neoplasms; probability; colorectal tumor; folinic acid; reference values; maximum tolerated dose; platinum complex; drug administration; oxaliplatin; organoplatinum compounds; infusions, intravenous; leucovorin; drug pulse therapy; intravenous drug administration; reference value; pulse therapy, drug; humans; prognosis; human; male; female; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 22 |
| Issue: | 23 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2004-12-01 |
| Start Page: | 4753 |
| End Page: | 4761 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15570076 |
| DOI: | 10.1200/jco.2004.03.119 |
| DOI/URL: | |
| Notes: | J. Clin. Oncol. -- Cited By (since 1996):34 -- Export Date: 16 June 2014 -- Source: Scopus |
