CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II

Abstract

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m À2 ) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN þ ). Median age was 60 years (range 43 -75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2 -15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48 -0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.

Irinotecan and radiosensitization in rectal cancer

“…In this trial 33 patients with locally advanced rectal cancer (1 cT2, 29 cT3, 3 cT4, and 21 cN + ) were enrolled and treated in an otherwise identical manner [35]. Surgery with total mesorectal excision (TME) was performed within 1 week after the completion of radiation therapy.…”

Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications

“…On the other hand, Gollins et al [14], Aschele et al [22], Sato et al [23] as well as Voelter et al [8] report rather low anastomotic leakage rates of 6.4%, 2%, 0% and 6% respectively from a group of 31, 747, 67 and 21 patients with sphincter sparing surgery. All studies concerning an intensified neoadjuvant RCT regime lack either a substantial number of patients and are basically series without a control group or do not focus on the surgical outcome [5,15,22,23].…”

Therapie des frühen und lokal fortgeschrittenen Rektumkarzinoms

“…Irinotecan wurde im Rahmen einer Phase-I/II-Dosiseskalationsstudie (Tabelle 7) präoperativ mit einer akzelerierten hyperfraktionierten RT kombiniert [37]. 5-FU wurde nicht appliziert.…”