Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer

Abstract

SummaryThe purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg m -2 ) was given every 2 weeks and PVI 5-FU (300 mg m -2 day -1 ) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15-46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n = 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3-4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7-73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer.

Hypersensitivity and idiosyncratic reactions to oxaliplatin

“…Table 1 summarizes the reported incidence in various clinical trials in patients with advanced colorectal carcinoma who received a 2‐hour infusion of oxaliplatin in combination with 5‐FU/leucovorin 5–24. Based on these published results, the incidence was 0.55%.…”

Oxamusplatin: a cytotoxic Pt(ii) complex of a nitrogen mustard with resistance to thiol based sequestration displays enhanced selectivity towards cancer

“…[15][16][17][18][19] In contrast, oxaliplatin with a trans-(R,R)-1,2-diaminocyclohexane (DACH) carrier ligand and oxalato leaving group show less systemic toxicity. 13,[20][21][22] Oxaliplatin overcomes CDDP resistance due to the change in the carrier ligand that alters the type of DNA adducts formed. 13,[20][21][22] This strategy has inspired the generation of many excellent Pt (II/IV) complexes.…”

“…13,[20][21][22] Oxaliplatin overcomes CDDP resistance due to the change in the carrier ligand that alters the type of DNA adducts formed. 13,[20][21][22] This strategy has inspired the generation of many excellent Pt (II/IV) complexes. 7,11,23 A wide variety of Pt(II) complexes viz.…”

The Role of 5-Fluorouracil (5-FU) Reintroduction with Irinotecan or Oxaliplatin in Truly 5-FU-Refractory Advanced Colorectal Cancer Patients

“…Nevertheless, the subset of patients benefiting from this treatment strategy was those in whom treatment was interrupted after a response or disease stabilization. Few data exist exploring the role of continuous infusion of 5-FU in bolus 5-FU-resistant colorectal cancer patients, but some studies clearly demonstrated that patients refractory to bolus 5-FU might respond to continuous IV infusion [6, 9, 10, 11]. Recently Andre et al [12] suggested that the reintroduction of infusional 5-FU and oxaliplatin (FOLFOX) in patients pretreated with the same chemotherapy regimen could still show clinical activity in terms of response rate in advanced colorectal cancer.…”