Recent combinations of chemotherapy have significantly improved the response
rate and survival time for patients with metastatic colorectal cancer. This
improvement has been initially demonstrated with the combination of fluorouracil
(5-FU)/leucovorin and irinotecan (CPT-11, Camptosar), which now is considered
and recommended as first-line treatment. The combination of improved efficacy
with survival benefit should translate into a better cure rate in patients with
resected, locally advanced, nonmetastatic colorectal cancer for whom adjuvant
chemotherapy with 5-FU/leucovorin is of proven benefit. Several randomized phase
III trials are ongoing in Europe or would begin shortly to assess the potential
benefit of a 5-FU/leucovorin-irinotecan combination in the adjuvant setting
for patients with stage II or III colorectal cancer. This article will review
the inclusion criteria and goal of these European trials. An update on accrual
and on tolerance will also be provided. [ONCOLOGY 16(Suppl 3):13-15, 2002]
In industrialized countries,
colorectal cancer is the most frequently occurring cancer in adults. A positive effect on cure rate has been seen over
the past decade with the use of adjuvant therapy, but about 50% of patients
diagnosed with colorectal cancer still will die eventually from metastatic
disease. An estimated 30% of patients probably have overt metastatic disease at
the time of surgical resection.
In patients whose tumors extend through the bowel wall to regional lymph
nodes (International Union Against Cancer stage III), adjuvant therapy
consisting of a leucovorin-biomodulated fluorouracil (5-FU) regimen improves
survival time. The role of adjuvant therapy in the treatment of stage II
colorectal cancer in which lymph nodes are not affected is not yet defined and
remains under investigation.
The combination of irinotecan (CPT-11, Camptosar), a topoisomerase I
inhibitor, with the standard 5-FU/leucovorin regimen has been shown to improve
both response rate and survival in previously untreated patients with advanced
colorectal cancer as compared with that achieved with 5-FU/leucovorin
alone.[1,2] This improved efficacy in first-line therapy of metastatic
colorectal cancer should translate into a better control of micrometastases and
improvement of 5-year survival rate. Ongoing trials in Europe that are assessing
the use of irinotecan in combination therapy for adjuvant treatment of
colorectal cancer are presented in this article, with an update on the status of
Five randomized trials of irinotecan in the adjuvant setting are either
planned or ongoingfour in colon cancer and one in rectal cancer patients (Table
1). These trials aim to evaluate the effects of adding irinotecan to
5-FU/leucovorin on survival in patients receiving adjuvant treatment.
Aventis V307 (PETTAC 3)
V307, the Aventis-sponsored trial, started in September 1999. This study,
chaired by E. van Cutsem, is designed mainly to assess the role of irinotecan in
addition to infusional 5-FU/leucovorin in patients with stage III colon cancer.
Stage II patients are also eligible for the study at the physician’s
discretion. Patients are assigned randomly to receive 5-FU/leucovorin alone or
5-FU/leucovorin plus 80 mg/m² of irinotecan weekly or 180 mg/m² of irinotecan
given every 2 weeks.
1. Douillard JY, Cunningham D, Roth AD, et al: Irinotecan combined with
fluorouracil compared with fluorouracil alone as first-line treatment for
metastatic colorectal cancer:A multicentre randomized trial. Lancet 355:1041-1047, 2000.
2. Saltz LB, Cox JV, Blanke C, et al: Irinotecan plus fluorouracil and
leucovorin for metastatic colorectal cancer. New Engl J Med 343:905-914, 2000.