Phase I study of irinotecan by 24-h intravenous infusion in combination with 5-fluorouracil in metastatic colorectal cancer.

Abstract

BACKGROUND:

This study was intended to ascertain the feasibility of a combination therapy with irinotecan by 24-h intravenous infusion (24-h CPT-11) and 5-fluorouracil (5-FU) for patients with metastatic colorectal cancer, to estimate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD), to determine the recommended dose (RD) for the Phase II study, and to evaluate the efficacy of the combination therapy.

METHODS:

The dosage regimen was as follows: CPT-11 was given by 24-h CPT-11 on day 1, followed by 24-h intravenous infusion of 5-FU on day 2. This regimen was repeated every 2 weeks. The dose of CPT-11 was escalated in five steps from 50 to 75, 100, 125, or 150 mg/m(2) (levels 1-5), whereas the dose of 5-FU was fixed at 800 mg/m(2).

RESULTS:

Twenty-six patients were recruited for this study, and 25 of the 26 patients were eligible for the assessment. The DLTs of 24-h CPT-11/5-FU therapy included grade 3 diarrhea in 1 patient treated at level 1, and grade 3 neutropenia in 1 patient and grade 4 neutropenia in 1 patient at level 4. In level 5, in 3 cases the next administration could not be done for 22 days or more as a consequence of anorexia. Thus, the level 5 was made a MTD and the level 4 was made a RD. The main side effects of grade 3 or higher, although nausea/vomiting occurred, were mild and tolerable in severity overall. The overall response rate was 24.0% (6PR/25).

CONCLUSION:

This study suggests that 24-h CPT-11/5-FU therapy is feasible and effective for treatment of metastatic colorectal cancer.

• Authors: Mariko Kambe, Hiroaki Kikuchi, Makio Gamo, Takashi Yoshioka, Yasuo Ohashi, Ryunosuke Kanamaru
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 17 Issue 2 Pg. 150-4 (Apr 2012) ISSN: 1437-7772 [Electronic] Japan
• PMID: 21786211 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, blood, pharmacokinetics)
• Colorectal Neoplasms (drug therapy, pathology)
• Diarrhea (chemically induced)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Infusions, Intravenous
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Neutropenia (chemically induced)