Phase II randomised trial of raltitrexed–oxaliplatin vs raltitrexed–irinotecan as first-line treatment in advanced colorectal cancer

Abstract

The purpose of this phase II randomised trial was to determine which of two schemes, raltitrexed-irinotecan or raltitrexed-oxaliplatin, offered better activity and less toxicity in patients with advanced colorectal cancer (CRC). A total of 94 patients with previously untreated metastatic CRC were included and randomised to receive raltitrexed 3 mg m À2 followed by oxaliplatin 130 mg m À2 on day 1 (arm A), or CPT-11 350 mg m À2 followed by raltitrexed 3 mg m À2 (arm B). In both arms treatment was repeated every 3 weeks. Intent-to-treat (ITT) analysis showed an overall response rate of 46% (95% CI, 29.5 -57.7%) for arm A, and 34% (95% CI, 19.8 -48.4%) for arm B. Median time to progression was 8.2 months for arm A and 8.8 months for arm B. After a median follow-up of 14 months, 69% of patients included in arm A were still alive, compared to 59% of those included in arm B. Overall, 31 patients (65%) experienced some episode of toxicity in arm A and 32 patients (70%) in arm B, usually grade 1 -2. The most common toxicity was hepatic, with 29 patients (60%) in arm A and 24 patients (62%) in arm B, and was grade 3 -4 in four (8%) and four (9%) patients, respectively. In all, 14 patients (29%) from arm A and 24 patients (52%) from arm B had some grade of diarrhoea (Po0.03). Neurologic toxicity was observed in 31 patients (64%) in arm A, and was grade 3 -4 in five patients (10%), while a cholinergic syndrome was detected in nine patients (19%) in arm B. There were no differences in haematologic toxicity. One toxic death (2%) occurred in arm A and three (6.5%) in arm B. In conclusion, both schemes have high efficacy as first-line treatment in metastatic CRC and their total toxicity levels are similar. Regimens with raltitrexed seem a reasonable alternative to fluoropyrimidines.

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

“…On the basis of the predefined eligibility criteria, we selected 12 studies [3][4][5][7][8][9][10][11][12][13][14][15] that fulfilled the qualitative and quantitative requirements of the systematic analysis. A total of 735 patients were enrolled across the selected trials (range, 37-94).…”

“…Aparicio et al [7] Carnaghi et al [4] Cascinu et al [3] Chiara et al [8] Feliu et al [10] Feliu et al [9] TOMIRI Feliu et al [9] TOMOX Gravalos et al [5] Martoni et al [11] Neri et al [12] Santini et al [13] Seitz et al [15] Scheithauer et al [14] 0 required, unlike fluoropyrimidines [1]. In addition, results reported at the American Society of Clinical Oncology meeting in 2000 suggest that the prophylactic use of the 5-HT3 antagonist ondansetron reduces the severity of nausea and diarrhea, preventing dehydration, and the use of dexamethasone reduces the incidence of fever and fatigue [23].…”

Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis

“…It has the same target as FUDR, but their mechanisms of action are different [21]. Raltitrexed has been widely used for the treatment of metastatic CRC, alone or in combination with oxaliplatin [22][23][24]. The combination of raltitrexed and oxaliplatin shows response rates of 41-54% and median survival times of 14.6-15.6 months for metastatic CRC [25][26][27][28].…”

Cost-Effectiveness Analysis of First-Line Chemotherapies in Metastatic Colorectal Cancer

“…Two large multicenter trials, in Great Britain and France, are addressing this question and hopefully answers will be provided in approximately 2 years. New aggressive protocols combining raltitrexed with oxaliplatin or irinotecan are currently evaluated in phase II studies, either in first- or second-line treatment of metastatic colorectal cancer [27,28,29,30]. …”