A retrospective study of bifractionated CPT-11 with LF5FU infusion (FOLFIRI-3) in colorectal cancer patients pretreated with oxaliplatin and CPT-11 containing chemotherapies.
A retrospective study of bifractionated CPT-11 with LF5FU infusion (FOLFIRI-3) in colorectal cancer patients pretreated with oxaliplatin and CPT-11 containing chemotherapies
Viel E, Demarchi MD, Chaigneau L et al.
Am J Clin Oncol, 2008, 31, 89-94
This article presents the results of a retrospective monocentric study conducted to assess the efficacy and tolerability of a FOLFIRI-3 regimen in patients with metastatic colorectal cancer (CRC) previously treated with chemotherapies containing oxaliplatin and CPT-11.
The FOLFIRI regimen is considered a standard of treatment in first-line therapy for CRC, but the poor results of this regimen in second-line therapy led to the development of the FOLFIRI-2 and FOLFIRI-3 regimens. Preclinical evidence suggested that the antiproliferative activity of the 5-FU and CPT-11 combination is schedule-dependent: in vitro the major antineoplastic effects were observed when irinotecan was administered before 5-FU. The FOLFIRI-2 regimen was demonstrated to be effective but associated with major side effects. The FOLFIRI-3 regimen, however, has proved its efficacy and safety as second-line therapy with oxaliplatin-pretreated patients.
In this retrospective study, 27 metastatic CRC patients previously exposed to irinotecan and/or oxaliplatin were treated with the FOLFIRI-3 regimen as second-line therapy. The median age was 63.6 years (range 49-76), and 63% of the patients were males. Fifty-nine per cent of the patients had colon carcinoma and 41% had rectal carcinoma. All of the patients had already received chemotherapy containing irinotecan, and 96% had received oxaliplatin. The FOLFIRI-3 regimen was administered every 14 days: on day 1 irinotecan, 100 mg/[m.sup.2], as a 1-hour infusion running concurrently with calcium folinate 400 mg/[m.sup.2], as a 2-hour infusion, followed by 5-FU, 2400 mg/[m.sup.2], as a 46-hour infusion. On day 3 irinotecan, 100 mg/[m.sup.2], was again infused after the end of the 5-FU infusion. The median number of cycles administered was 7.6 (range 1-18). The most frequent cause of treatment disruption was disease progression. In only one case was the treatment interrupted due to toxicity.
The FOLFIRI-3 regimen was well tolerated: there were few adverse events and usually less than grade 2. The most frequently reported were nausea, vomiting, diarrhoea, mucositis, anaemia and neutropenia. Grade 3 and 4 toxicities were observed: nausea (11%), diarrhoea (11%), anaemia (7.4%) and neutropenia (7.4%). The level of partial response was 7.4%, while 37% of patients achieved stable disease. Time to progression was 4.47 months (range 0-11) and median overall survival was 8.9 months (range 0.72 -21.4).
These results are consistent with those reported in studies evaluating the role of FOLFOX, capecitabine and cetuximab in metastatic CRC pretreated with 5-FU and irinotecan (but we have to remember that in this study only 27 patients were evaluated). This study suggests that the FOLFIRI-3 regimen is an effective and safe regimen in pretreated (also with CPT-11) patients with metastatic CRC. The fractionated administration of irinotecan might restore chemosensitivity in patients resistant to FOLFIRI.
Commentary by Roberto Labianca
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|Publication:||Advances in Gastrointestinal Cancer|
|Article Type:||Clinical report|
|Date:||Sep 1, 2008|
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