High-dose continuous infusion folinic acid and bolus 5-fluorouracil in patients with advanced colorectal cancer: a phase II study.

Abstract

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

Hepatic Resection After Rescue Cetuximab Treatment for Colorectal Liver Metastases Previously Refractory to Conventional Systemic Therapy

“…Using mainly systemic FU-LV and oxaliplatincontaining chronomodulated regimens, we have demonstrated the ability to convert 14% of patients from an unresectable status to a resectable situation, with a postoperative 5-year survival rate of 33%. [8][9][10] More recently, however, the addition of biologic agents (bevacizumab or cetuximab) to cytotoxic chemotherapy has increased the rate and extent of tumoral responses, [11][12][13] suggesting that the addition of these agents to second-line or higher line regimens could improve resectability rates in treatment-refractory patients. [3][4][5][6] Although the combination of systemic chemotherapy and liver surgery can convert a significant proportion of patients from a palliative situation to a potentially curative situation, the majority of initially unresectable liver metastases do not respond sufficiently to initial chemotherapy to become resectable.…”

Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure

“…Using optimal regimens , objective tumour responses may be expected in 25-30% of cases and are generally of short duration. Second-line therapeutic options have long been very disappointing (Ahlgren et al, 1991;Bertrand et al, 1992) and until recently patients were usually not offered alternative treatment after 5FU failure. However, encouraging preliminary results have been recently published using continuous 5FU (Izzo et al, 1992) with response rates of 16%.…”

Developments of the fluoropyrimidines as inhibitors of thymidylate synthetase: Pharmacologic and clinical aspects

“…Antitumor activity of S'dFUrd in humans is probably similar to that observed with S-FU [28,29]. However, at the posologies and schedules used in the clinics, the drug induced prohibitive neurologic toxicity and cardiac abnormalities which render its use extremely difficult in humans [28,29], There are new attempts at synthesis of other prodntgs Bertrand et al [39] 15 Budd et al [40] 53 54 Schmoll et al [41] 68 Petrelli et al [ of the 5'dFUrd-type. The aim is to produce a compound that would be a better substrate for uridine phosphorylase than 5'dFUrd, leading to enhanced release of 5-FU within the cell.…”

“…Since 1982, a number of phase I1 studies have been reported in patients with colorectal, gastric, and more recently, breast carcinomas. In colorectal carcinoma patients who were not previously treated with chemotherapy, the mean response rate calculated from 16 available studies [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] was 31%, ranging from 15-54% (Table I). In patients who Bruckner et al [35] Madajewicz et al I371 Cunningham et al [38] Byrne et al [50] Valone et al [51] Bertrand et al 1521 Laufman et al [44] Hines et al [ were previously treated with chemotherapy [33][34][35]37,38,44, the mean response rate obtained in nine trials was 15% (range, 0-50%) ( Table 11).…”