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(Drug information on fluorouracil) (5-FU)/leucovorin and irinotecan(Drug information on 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 each.
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.