Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer

Aparicio, Jorge; Vicent, J. M.; Maestu, I.; Garcera, S.; Busquier, Isabel; Bosch, C.; Llorca, C.; Díaz, Roberto; Fernández-Martos, Carlos; Galán, Antonio

doi:10.1093/annonc/mdg285

Cited by 24 publications

(30 citation statements)

References 26 publications

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“…The observed pattern of toxicity resembles that described in previous phase I–II trials of the same combination [9,10,11,12,13,14]. Hematological toxicity and mucositis seem to be lower than with combinations of 5-FU and CPT-11, whereas diarrhea, emesis, and asthenia are somewhat higher.…”

Section: Discussionsupporting

confidence: 80%

“…CPT-11, 350 mg/m 2 was administered as a 60-min infusion followed 1 h later by raltitrexed, 3 mg/m 2 administered as a 15-min infusion, both in a thrice-weekly schedule. This one-day schedule was selected by the consistent phase I data existing and our group’s previous experience [9, 11, 12]. Atropine prophylaxis and antiemetics (dexamethasone plus antiserotoninergic) were routinely prescribed.…”

Section: Methodsmentioning

confidence: 99%

“…Preclinical data suggest a synergistic activity between CPT-11 and raltitrexed and three recent phase I studies have shown that single-agent full doses of both drugs can be safely given thrice-weekly [9,10,11]. The reported efficacy ranged from 15.4% (in second-line) [12] to 34–46% (in first-line treatment) [13,14] in only two of three phase II studies published to date.…”

Section: Introductionmentioning

confidence: 99%

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First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

Aparicio

Vicent²,

Maestu³

et al. 2005

Oncology

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Objectives: The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment. Methods: Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m²) plus raltitrexed (3 mg/m²), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity. Results: A total of 331 cycles were administered, with a median of five cycles per patient (range, 1–16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18–44%). The incidence of grade 3–4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months. Conclusions: The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

Aparicio

Vicent²,

Maestu³

et al. 2005

Oncology

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“…In agreement with these authors, we consider that this administration approach could be more convenient for patients. This same regimen has been used as second-line therapy in a series of 52 patients with 5FU-resistant CRC, where a partial response rate of 13.5% was obtained with moderate toxicity (grade 3 -4 diarrhoea, 23%; grade 3 -4 neutropenia, 17%) (Aparicio et al, 2003). Other authors, however, have investigated the activity and tolerance of CPT-11 administration followed by raltitrexed 24 h later (Stevenson et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study

et al. 2004

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To evaluate the efficacy and toxicity of irinotecan (CPT-11) in combination with raltitrexed as first-line treatment of advanced colorectal cancer (CRC). A total of 91 previously untreated patients with advanced CRC and measurable disease were enrolled in this phase II study. The median age was 62 years (range 31 -77); male/female 54/37; ECOG performance status was 0 in 50 patients (55%), one in 39 (43%) and two in two (2%). Treatment consisted of CPT-11 350 mg m À2 in a 30-min intravenous infusion on day 1, followed after 30 min by a 15-min infusion of raltitrexed 3 mg m À2 . Measurements of efficacy included the following: response rate, time to disease progression and overall survival. Of the 83 evaluable patients valuable to objective response, there were five complete responses (6%) and 23 partial responses (28%), for an overall response rate of 34% (95% CI: 25.9 -46.5%). In all, 36 patients (43%) had stable disease, whereas 19 (23%) had a progression. The median time to progression was 11.1 months and the median overall survival was 15.6 months. A total of 487 cycles of chemotherapy were delivered with a median of five per patient. Grade 3 -4 WHO toxicities were as follows: diarrhoea in 13 patients (15%), nausea/vomiting in four (4%), transaminase increase in six (7%), stomatitis in two (2%), febrile neutropenia in three (3%), anaemia in five (6%) and asthenia in three (3%). The combination CPT-11 -raltitrexed is an effective, well-tolerated and convenient regimen as front-line treatment of advanced CRC.

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“…These polyglutamates are approximately 60-to 100-fold more active than the parent compound and are retained intracellularly [3,4]. In phase III studies in advanced CRC the agent showed similar efficacy to 5-fluorouracil and leucovorin with a less toxicity and a more convenient every three-week schedule [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)

et al. 2010

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Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer

Abstract: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.

Cited by 24 publications

References 26 publications

First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study

A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)

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