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

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.

Topoisomerase I and IIα protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy

“…Irinotecan yielded response rates of 15–25% in 5-FU-refractory patients [ 36 – 44 ], not dissimilar to those observed in first-line treatment of colorectal cancer (18–32%) [ 45 – 47 ] and in contrast to the expected decreasing response rate from the application of irinotecan in second-line treatment. Treating patients with irinotecan upon progression to 5-FU/LV seems to be yielding more significant results compared to the opposite sequence, based in our previous experience, where the best results with sequential monotherapies were obtained when 5-FU/LV was followed by irinotecan (5-FU/LV → CPT11) at disease progression or relapse [ 41 ].…”

Characterization of 5-Fluorouracil-Resistant Cholangiocarcinoma Cell Lines

“…Chemotherapy is thus considered a preferred treatment option in order to prevent postsurgical cancer recurrence [4] . 5-Fluorouracil (5-FU) is a standard chemotherapeutic agent used to treat many types of cancers [5,6] , and indeed is currently used in the palliative treatment of CCA. However, clinical studies have demonstrated a relatively poor response rate (0-40%) of this cancer to 5-FU chemotherapy [7] .…”

Safety and Efficacy of Modified FOLFOX6 for Treatment of Metastatic or Locally Advanced Colorectal Cancer

“…A total of 95 patients (84.8%) were further treated with other chemotherapy regimens, which mainly included irinotecan ( table 2 ). [14], irinotecan and UFT (uracil and tegafur) with or without oral LV [17], TS-1 (1 M tegafur + 0.4 M gimestat + 1 M otastat potassium) and irinotecan [18], and irinotecan alone [19]. 2 Regimens that did not include irinotecan were Roswell Park Memorial Institute regimen (RPMI) [20], UFT with or without oral LV [21], TS-1 and hepatic arterial infusion of 5-FU [22].…”