Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion

Abstract

The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation. The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42-92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6-61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups. Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I and Pharmacokinetic Study of the Polyamine Synthesis Inhibitor SAM486A in Combination with 5-Fluorouracil/ Leucovorin in Metastatic Colorectal Cancer

“…In seven (27%) patients, somnolence grade 1 was observed. Skin toxicity, particularly hand-foot syndrome, was seen in 15 patients (58%); however, in only one patient at the dose level of 125 mg/m 2 did hand and foot syndrome toxicity exceed grade 2 resulting in a dose reduction of 5-FU/LV and cotreatment with pyridoxine (19). Only one patient at the dose level of 125 mg/m 2 did have one episode of neutropenic sepsis.…”

Comparative Assessment of Skin and Subcutaneous Toxicity in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

“…Topical corticosteroids have an effective role in the management of symptoms however these may also cause thinning of the skin (Komamura et al, 1995;Vakalis et al, 1998), which was observed in some female patients in our study. The patients were also prescribed with Vitamin B6, which is known to be highly effective in both the prophylaxis and control of symptoms (Fabian et al, 1990). Other than HFS, there were no other symptoms of grade 3 in the patients of FOLFOX 4 pertaining to skin and subcutaneous toxicity (Figure 2A).…”

Cyclophosphamide, methotrexate and infusional 5-fluorouracil (infusional CMF) in metastatic breast cancer

“…Palmar-plantar erythrodysthesia, a potential complication of infusional 5-fluorouracil therapy, was treated with pyridoxine 50 mg t.i.d., p.o. (Fabian et al, 1990). The infusion was continued until disease progression or 24 weeks of treatment had been completed.…”