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High-dose chronomodulated infusion of 5-fluorouracil (5-FU) and folinic acid (FA) (FF5–16) in advanced colorectal cancer patients

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Abstract

Purpose

. The best way to deliver infusional 5-fluorouracil (5-FU) and folinic acid (FA) has yet to be determined. The aim of this prospective phase II trial was to verify the tolerability, activity and efficacy of chronomodulated 5-FU-FA (FF5–16) every 3 weeks in 48 untreated patients (group A), and 28 pretreated and four non-measurable, advanced colorectal cancer (ACC) patients (group B).

Methods

The sinusoidal delivery of both drugs started at 10.00 p.m. and ended at 10.00 a.m., with peak flow at 4.00 a.m. for 5 consecutive days. The initial 5-FU dose was 900 mg/m2/day with intra-patient dose increase at 1,000 and 1,100 mg/m2/day, at the second and third course, respectively; FA was injected at a fixed dose of 150 mg/m2/day (Garufi et al.1997).

Results

Neither death from toxicity nor hematological toxicities were encountered. Maximal toxicity consisted of Grade 3 oral mucositis in 41% of patients, in only 8% of 535 courses. It was possible to achieve objective responses in 31% of untreated patients, with a progression free survival (PFS) of 7 months, median survival of 14 months and a 2-year survival rate of 28%. Similar results for PFS and survival were obtained in pretreated patients as well. Univariate analysis and multivariate analysis showed that response was related to the occurrence of mucositis and diarrhea (p=0.03 and p=0.0007) and to performance status (PS) (p=0.01). Quality of life, measured with the EORTC QLQ-C30+3 questionnaire, was unaffected by treatment and was better in patients with good PS and responsiveness.

Conclusions

In this chronomodulated FF5–16 phase II study, the probability of obtaining a relevant tumor reduction was significantly correlated with a patient variable such as PS, and toxicity variables such as mucositis and diarrhea. This observation and the validation of predictive factors for QoL deserve further investigation in ACC patients.

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Authors and Affiliations

  1. SC Oncologia Medica C, Istituto Regina Elena, Istituti Fisioterapici Ospitalieri, Via E. Chianesi, 53, 00144 , Rome, Italy

    Edmondo Terzoli, Carlo Garufi, Albina Rita Zappalà, Barbara Vanni, Giancarlo Antonini Cappellini & Anna Maria Aschelter

  2. Psicologia, Istituto Regina Elena, Rome, Italy

    Patrizia Pugliese & Maria Perrone

  3. Statistica, Istituto Regina Elena, Rome, Italy

    Diana Giannarelli

Authors
  1. Edmondo Terzoli
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  2. Carlo Garufi
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  3. Albina Rita Zappalà
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  4. Barbara Vanni
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  5. Patrizia Pugliese
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  6. Giancarlo Antonini Cappellini
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  7. Anna Maria Aschelter
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  8. Maria Perrone
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  9. Diana Giannarelli
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Correspondence to Edmondo Terzoli.

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Terzoli, E., Garufi, C., Zappalà, A.R. et al. High-dose chronomodulated infusion of 5-fluorouracil (5-FU) and folinic acid (FA) (FF5–16) in advanced colorectal cancer patients. J Cancer Res Clin Oncol 130, 445–452 (2004). https://doi.org/10.1007/s00432-004-0560-0

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