Clinical Study

Sequential Administration of 5-Fluorouracil (5FU)/Leucovorin (LV) Followed by Irinotecan (CPT-11) at Relapse versus CPT-11 Followed by 5-FU/LV in Advanced Colorectal Carcinoma
A Phase III Randomized Study
Nicolas Tsavaris^a, Christos Kosmas^f, Helias Skopelitis^a, Nicitas Papadoniou^g, Aristidis Polyzos^b, George Zografos^b, Efstathios Adoniou^c, John Gryniatsos^d, Evangelos Felekouras^d, Michalis Zacharakis^a, Francheska Sigala^d, Christos Bacoyiannis^d, George Papastratis^e, Efstathios Papalambros^d

Oncology Units,
^aDepartment of Pathophysiology and
^bFirst Department of Propedeutic Medicine,
^cSecond Department of Surgery and
^dFirst Department of Surgery, Laikon General Hospital, University of Athens School of Medicine, and
^eThird Department of Surgery, G. Gennimatas General Hospital, Athens,
^fDepartment of Gastroenterology, General Hospital of Rhodes, Rhodes, and
^gSecond Department of Medical Oncology, 'Metaxa' Cancer Hospital, Piraeus, Greece

Address of Corresponding Author

Chemotherapy 2007;53:282-291 (DOI: 10.1159/000102583)

  Key Words

• Colorectal cancer
• 5-Fluorouracil
• Irinotecan
• Leucovorin

  Abstract

Purpose: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). Patients and Methods: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m² LV and 425 mg/m² 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m²), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. Results: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. Conclusions: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Nicolas Tsavaris, MD
Department of Pathophysiology, Athens University School of Medicine
Laikon General Hospital
GR-11527 Athens (Greece)
Tel./Fax +30 10 646 3191, E-Mail tsavari1@otenet.gr

  Article Information

Received: October 31, 2005
Accepted after revision: May 2, 2006
Published online: May 10, 2007
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 6, Number of References : 33