A Randomised Phase II Study of Irinotecan in Combination with 5-FU/FA Compared with Irinotecan Alone as Second-Line Treatment of Patients with Metastatic Colorectal Carcinoma

Abstract

We conducted a randomised phase II study to compare irinotecan monotherapy with irinotecan in combination with infusional 5-fluorouracil/folinic acid (5-FU/FA) regarding efficacy and safety of these regimens in second-line therapy after failed fluoropyrimidine therapy in patients with metastatic colorectal cancer (mCRC). Patients and Methods: 55 patients with mCRC after failure of a first-line therapy were randomised to receive either irinotecan 80 mg/m2 followed by FA 500 mg/m2 and 5-FU 2,000 mg/m2 24 h weekly for 6 weeks, with courses repeated on day 50 (arm A), or irinotecan 125 mg/m2 weekly for 4 weeks, with cycles repeated on day 43 (Arm B). Results: Both regimens yielded a partial response rate of 11% with identical progression-free survival (3.7 months for both regimens) and similar overall survival (9.5 months for the combination therapy vs. 10.7 months for the monotherapy). Both regimens were very well tolerated, and the combination of irinotecan with 5-FU/FA did not result in increased toxicity. Conclusion: Our study confirms that irinotecan alone or in combination with infusional 5-FU/FA is an effective and safe regimen for CRC patients who failed first-line therapies. However, the role of 5-FU in addition to irinotecan for fluoropyrimidine failures remains unclear. Due to the small sample size, a decision cannot be made which therapy should be preferred, and a significant contribution to the efficacy of single-agent irinotecan is not obvious from this small randomised phase II trial.

Systematic review of benefits and risks of second-line irinotecan monotherapy for advanced colorectal cancer

“…In 10 study samples, irinotecan was administered 3-weekly, using a dose of 350 mg/m 2 [5,17,19,20,23,25,29,30,33,35]. In seven study samples, irinotecan was administered weekly for 4 consecutive weeks, using a dose of 125 mg/m 2 , followed by a 2-week rest period [15,16,18,22,26,35,37]. The remaining 14 study samples used other regimens, including dose variations on the 3-weekly schedule [21,30] and the weekly schedule [14,18,28,32].…”

DC Bead™: a major development in the toolbox for the interventional oncologist

“…The DC Bead does, however, have some interaction with certain campothecin analogues, such as irinotecan [17] and topotecan hydrochloride [18], again owing to the presence of a resident positive charge on the tertiary amine groups of these salts (Figure 1). Irinotecan has been used as a monotherapy to treat certain patients with mCRC and in combi nation with other drugs in many first-and second-line regimens [19]. Combining the DC Bead with irinotecan is, therefore, the preferred option for controlling liver-dominant disease and has shown considerable early promise [20,21].…”

Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model

“…Although surgical resection in selected patients can achieve 25–45 % 5-year survival, in all other patient groups it is less than 5 %. Systemic chemotherapy can palliate symptoms and improve survival and in recent years the topoisomerase I inhibitor irinotecan, has been approved for use in combination with 5-FU/folinic acid in patients without prior chemotherapy and for the second-line treatment of this disease as a single agent in patients who have failed an established 5-FU-containing treatment regimen [1]. …”