5-Fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: a multicenter randomised phase II study of the Southern Italy Oncology Group.

Abstract

PURPOSE:

The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial.

PATIENTS AND METHODS:

A total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of age > or = 70 and < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT-11 regimen, arm B 68 patients). Both treatments were repeated every two weeks. The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen.

RESULTS:

Thirty-three and sixty-four patients were evaluable in arm A and B, respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median duration of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 vs. 10 months, P = 0.0016). All patients were evaluable for toxicity which was mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms.

CONCLUSIONS:

The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literature, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.

• Authors: E Maiello, V Gebbia, F Giuliani, G Paoletti, N Gebbia, S Cigolari, S Fortunato, T Pedicini, N Borsellino, M Lopez, G Colucci
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 11 Issue 8 Pg. 1045-51 (Aug 2000) ISSN: 0923-7534 [Print] England
• PMID: 11038044 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Controlled Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Colorectal Neoplasms (drug therapy, pathology)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Infusions, Intravenous
• Injections, Intravenous
• Irinotecan
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Treatment Outcome