Australian experience of a modified schedule of FOLFOX with high activity and tolerability and improved convenience in untreated metastatic colorectal cancer patients

Abstract

This study determined the efficacy and safety of a modified FOLFOX regimen that improved patient convenience without compromising oxaliplatin dose intensity. A total of 62 patients with previously untreated metastatic colorectal cancer were enrolled to receive, entirely as outpatients, 2-weekly cycles of oxaliplatin 100 mg m À2 i.v. over 2 h, together with leucovorin 400 mg m À2 over 2 h, 5-fluorouracil (5-FU) 400 mg m À2 , bolus, followed by a 46-h infusion of 5-FU at 2.4 g m À2 . Treatment was given until progression or unmanageable toxicity. In all, 61 patients received Xone oxaliplatin dose and a median of 11 treatment cycles (range 1 -20 cycles); 22 (36%) reported grade 3/4 neutropenia and 13 patients (21%) experienced grade 3 neurotoxicity; 16 patients (26%) discontinued treatment due to disease progression or death, 15 (25%) due to neurotoxicity and six (10%) due to haematological toxicity. Of the 56 eligible patients, complete or partial responses were observed in 29 or 52% (95% confidence interval 38 -65%). Median progression-free survival was 8.2 months (7.1 -9.9) and median overall survival was 18.7 months (14.0 -23.4). In our experience, a modified schedule of FOLFOX improves convenience without compromising efficacy or toxicity. British Journal of Cancer (2005) Oxaliplatin unlike cisplatin has demonstrated activity against colon carcinoma cell lines in vitro and has also shown synergistic activity in experimental models (Raymond et al, 1997). Several large randomised trials have confirmed the efficacy of the oxaliplatin/5-fluorouracil (5-FU)/leucovorin (LV) combination as first-line therapy in metastatic colorectal cancer. In De Gramont's et al (2000) phase III trial, FOLFOX4 was significantly superior to the infusional regimen, LV5FU2, in response rate and progressionfree survival (PFS) and the combination of chronomodulated 5-FU/LV and oxaliplatin produced a significantly higher response rate and superior PFS to the 5-FU/LV regimen alone (Giacchetti et al, 2000). In a recent three-arm study in 796 untreated patients with metastatic colorectal cancer (Goldberg et al, 2004), FOLFOX4 was significantly superior to the irinotecan and bolus 5-FU/LV combination (IFL) and a third regimen of oxaliplatin plus irinotecan (IROX) in response rate, time to progression and overall survival, and induced fewer Grade 3 or 4 toxicities.The original FOLFOX4 regimen, however, does have drawbacks for patients, as it requires intravenous treatment in hospital for 48-h every 2 weeks. Several variations of this regimen, incorporating oxaliplatin dose intensification or simplification of the LV/5-FU schedule, have been evaluated in clinical trials.A retrospective analysis by Maindrault-Goebel et al (2000) of three phase II studies, in previously treated patients, using three different FOLFOX regimens showed that increased oxaliplatin dose intensity (485 mg m À2 ) improved response rates and PFS without compromising tolerability. One of the more effective regimens, FOLFOX6, utilised an oxaliplatin dose of 100 mg m À2 on da...

FOLFOX-4 Stop and Go and Capecitabine Maintenance Chemotherapy in the Treatment of Metastatic Colorectal Cancer

“…Furthermore, the median RD (9.2 months) and median PFS (8.6 months) were comparable with those usually observed with L-HOP-based combinations [1, 9,14]. However, the low progressive disease rate (9.4%) and the high percentage of patients that went on to surgical resection of metastases (15.6%) perhaps may reflect a better than average group performance with regard to patient selection, as is always the hazard of phase II trials.…”

“…In a recent multicenter randomized trial, severe neurotoxicity was observed in 18% of patients after a median of 12 FOLFOX-4 cycles; the median PFS was 8.7 months [14]. Another recent study about a modified FOLFOX regimen, in which L-HOP was used at a dose of 100 mg/m 2 , reported comparable PFS (8.2 months), but a higher incidence of severe neurotoxicity (21%) compared to our population study [9]. …”

“…L-HOP-induced cumulative neurotoxicity develops progressively in 10–15% of patients after a cumulative dose of 780–800 mg/m 2 , corresponding to approximately nine cycles at the 85 mg/m 2 dose, which is the dose used in FOLFOX-4. Severe neuropathy with L-HOP-based regimens has been reported in the range of 17%–21% in the majority of trials [1, 3, 9, 10]. …”

A Retrospective Study of the Safety and Efficacy of a First-Line Treatment with Modified FOLFOX-4 in Unresectable Advanced or Recurrent Gastric Cancer Patients

“…A FOLFOX-4 regimen was identified as a tolerable and effective therapeutic modality in cases of advanced gastric cancer. Response rates range from 39 to 56%, TTP is from 5.2 to 7.1 months, and the median OS is between 8.6 and 11.4 months [3,8,12,18,19,20]. Despite the current numerous efforts of randomized trials in unresectable advanced or recurrent gastric cancer patients treated with the FOLFOX-4 regimen, only limited, globally accepted standard data have been established.…”

“…It is an effective agent with a different toxicity profile for the treatment of advanced gastric cancer patients in several phase II studies [9,10,11]. The combination of oxaliplatin, 5-FU and leucovorin (FOLFOX) has been the standard treatment for patients with metastatic or advanced colorectal cancers [12]. In comparison with cisplatin, FOLFOX has a low-toxicity profile, with substantially lower rates of myelosuppression, nephrotoxicity and ototoxicity but with at least equivalent antitumor activities [13].…”