Continuous-infusion 5-fluorouracil in metastatic colorectal cancer patients pretreated with bolus 5-fluorouracil: Clinical evidence of incomplete cross-resistance

Falcone, Alfredo; Cianci, C.; Pfanner, E.; Bertuccelli, M.; Brunetti, I.; Muttini, M. P.; Dargenio, F.; Ricci, Sergio; Conté, Pierfranco

doi:10.1093/oxfordjournals.annonc.a058813

Cited by 18 publications

(6 citation statements)

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“…Combinations of irinotecan or oxaliplatin with 5-FU and leucovorin for first-line therapy of metastatic CRC have demonstrated improved response rates and median survival times over 5-FU and leucovorin alone (1, 2). In addition, infusional 5-FU has replaced bolus 5-FU as a platform for combination chemotherapy based on decreased toxicity and improved efficacy (3, 4). In the initial study investigating the combination of oxaliplatin, 5-FU, and leucovorin (FOLFOX-4) for first-line therapy of metastatic CRC, there was a 50% objective response rate compared to 22% with infusional 5-FU/leucovorin (LV5FU2) alone (2).…”

Section: Introductionmentioning

confidence: 99%

A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin in Previously Untreated Patients with Metastatic Colorectal Cancer

Fisher

Kuo

Ramsey

et al. 2008

Clinical Cancer Research

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Purpose: We investigated the gefitinib, 5-fluorouracil (5-FU), leucovorin and oxaliplatin (IFOX) regimen as first-line therapy in patients with metastatic colorectal cancer. Experimental Design: Eligible patients had stage IV colorectal adenocarcinoma, and had not received prior chemotherapy for metastatic disease. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin, leucovorin, and 5-FU (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg orally daily throughout the 14-day cycle. Results: Forty-five patients were enrolled and were assessable for toxicity. Forty-three patients were assessable for response.Thirty-one of the 43 patients (72%) had either a complete or partial response by the Response Evaluation Criteria in Solid Tumors. Median overall survival was 20.5 months. Median time to progression was 9.3 months. Commonly encountered grade 3 or 4 toxicities included diarrhea in 67% of patients and neutropenia in 60%. Grade 2 acneiform skin rash typical of gefitinib occurred in 60% of patients. Conclusions: IFOX is an active first-line regimen in patients with metastatic colorectal adenocarcinoma, showing higher response rates but also increased toxicities compared with FOLFOX-4 alone in a similar patient population.Over the last 10 years, incremental gains in response rates and the median survival for patients with metastatic colorectal cancer have been achieved with the introduction of active new chemotherapeutic and biologically targeted agents. Combinations of irinotecan or oxaliplatin with 5-fluorouracil (5-FU) and leucovorin for first-line therapy of metastatic colorectal cancer have shown improved response rates and median survival times over 5-FU and leucovorin alone (1, 2). In addition, infusional 5-FU has replaced bolus 5-FU as a platform for combination chemotherapy based on decreased toxicity and improved efficacy (3,4). In the initial study investigating the combination of oxaliplatin, 5-FU, and leucovorin (FOLFOX-4) for first-line therapy of metastatic colorectal cancer, there was a 50% objective response rate compared with 22% with infusional 5-FU/leucovorin alone (2). The FOLFOX-4 regimen was also associated with a longer time to progression (9.0 months versus 6.2 months) and a trend toward improved overall survival. Although a direct comparison of FOLFOX-4 and irinotecan, 5-FU, and leucovorin in previously untreated patients showed that FOLFOX-4 was superior, a subsequent comparison of FOL-FOX-6 and folinic acid, 5-FU, and irinotecan showed no significant difference in efficacy (5, 6). This confirmed that both irinotecan and oxaliplatin are active agents against colorectal cancer, and selection of an appropriate regimen could focus on their different toxicity profiles.The effort to further improve the efficacy and tolerability of treatment for metastatic colorectal cancer has led to the discovery of new agents targeting cell-signaling molecules such as epidermal growth factor receptor (EGFR). EGFR expression has been shown in 60% to 80% of ...

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Section: Introductionmentioning

confidence: 99%

A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin in Previously Untreated Patients with Metastatic Colorectal Cancer

Fisher

Kuo

Ramsey

et al. 2008

Clinical Cancer Research

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“…Its biochemical modulation with leucovorin (LV) or its administration by continuous venous infusion (CI) has improved its activity, and responses have been observed in approximately 20–30% of patients [4, 8, 9]. In particular CI 5-FU has demonstrated some activity even in patients resistant to the bolus-based 5-FU chemotherapy [10, 11]. Because both the LV and the CI schedule should potentiate 5-FU cytoxicity by enhancing thymidylate synthase inhibition [12], several studies have combined LV with CI 5-FU, and some have reported promising results [13, 14, 15, 16, 17, 18].…”

Section: Introductionmentioning

confidence: 99%

Infusions of Fluorouracil and Leucovorin: Effects of the Timing and Semi-Intermittency of Drug Delivery

Falcone¹,

Allegrini²,

Antonuzzo

et al. 1999

Oncology

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Preclinical and clinical studies have demonstrated that the circadian modulation of 5-FU delivery may reduce toxicities and improve antitumor activity. However, the relative importance of the timing of 5-FU delivery has not been clinically addressed. The aims of this study were to determine the toxicities, the maximum tolerable doses and the activity of a regimen with 5-fluorouracil (5-FU) and leucovorin (LV) administered as a 14-day continuous infusion according to a flat or three different chronomodulated rhythms in patients with metastatic gastrointestinal carcinomas. A total of 113 patients entered the study and their characteristics were comparable among the four groups. Toxicities included mainly stomatitis and diarrhea, and a reduced toxicity was observed in all the three chronogroups that allowed the delivery of higher dose intensities. Response rates were not significantly different among the four groups. These results suggest that a reduction in 5-FU+LV toxicity and an increase in 5-FU dose intensity can be obtained by a nonsinusoidally circadian modulated infusion. However, the reduction in toxicity observed seems to be dependent mainly on the quasi-intermittency and not on the timing of 5-FU+LV delivery.

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“…The median time to progression for patients receiving second-line therapy is approximately 3 months and the median survival of these patients is 6-8 months. [12][13][14][15] A randomized phase III trial compared continuous infusion 5-FU to Irinotecan among patients who had failed prior treatment with a 5-FU regimen. 10 Only one partial response (PR) (0.7%) was observed among 134 patients treated with continuous infusion 5-FU and 6 (4.5%) PRs were observed in the irinotecan arm.…”

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confidence: 99%

Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucovorin

Reid

Freeman²,

Post³

et al. 2005

Cancer Gene Ther

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Continuous-infusion 5-fluorouracil in metastatic colorectal cancer patients pretreated with bolus 5-fluorouracil: Clinical evidence of incomplete cross-resistance

Cited by 18 publications

References 0 publications

A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin in Previously Untreated Patients with Metastatic Colorectal Cancer

A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin in Previously Untreated Patients with Metastatic Colorectal Cancer

Infusions of Fluorouracil and Leucovorin: Effects of the Timing and Semi-Intermittency of Drug Delivery

Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucovorin

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