Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer

Abstract

a Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/ or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatment, 19 patients were considered as chemo-resistant and 14 patients as chemo-refractory. OXA 110 mg/m 2 (over 2 h) and IRI 175 mg/m 2 (over 1 h) were delivered on day 1,

Bimonthly Chemotherapy with Oxaliplatin, Irinotecan, Infusional 5-Fluorouracil/Folinic Acid in Patients with Metastatic Colorectal Cancer Pretreated with Irinotecan- or Oxaliplatin-Based Chemotherapy

“…The combination of 5-FU, folinic acid, OHP and CPT-11 has been studied in colorectal cancer patients either untreated for metastatic diseases [30][31][32][33][34] or pretreated with 5-FU [24][25][26][27][28][29] . In a minority of the pretreated patients, 5-FU was administered as part of combination regimens with either CPT-11 and OHP 25,26,29 . Only the study of Stathopoulos et al 28 reports results obtained with the triple combination in patients all previously treated with FOLFIRI.…”

“…In most of these studies 5-FU was used as a protracted 25,30,32,33 or short (90 min) 34 infusion regimen, or as a hybrid regimen (bolus + infusion) 24,27,31 . In three studies 5-FU was administered as a bolus injection 26,28,29 . The majority of these studies constitute phase I-II trials since dose-finding for 5-FU 26 , FA 27 , CPT-11 26,27,30,33 and OHP 26,27,33 has been employed.…”

“…These findings along with the demonstration of synergism or additivity of the ternary combination of CPT-11, OHP and 5-FU in preclinical studies 23 , have attracted considerable attention to the ternary combination of these drugs in the clinic. This ternary combination has shown marked clinical activity in phase I-II trials performed in both previously treated [24][25][26][27][28][29] and untreated [30][31][32][33][34] metastatic colorectal cancer patients at doses comparable to those used in binary combinations. These results are consistent with the superiority of the ternary combination of these drugs over their binary combinations.…”

“…More rarely, fatal toxic episodes have been observed 34 . Despite these studies, there are still few data available on the use of this ternary combination as second-line treatment for patients pretreated with OHP-or CPT-11based chemotherapy 25,26,28,29 .…”

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group

“…We have already assessed this triplet in pre-treated patients with metastatic gastrointestinal carcinomas [27,28]. Here we report on the safety and activity of this regimen in untreated gastric cancer patients.…”