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11 Dec 2017
Combining the DASH (Dietary Approaches to Stop Hypertension) diet with low sodium intake reduces systolic blood pressure (SBP) in individuals with pre- and stage 1 hypertension, with progressively higher reductions at greater levels of baseline SBP, a recent study has shown.
Tristan Manalac, 5 days ago
Major depressive disorder (MDD) appears to be more prevalent in females than in males, particularly in those who are divorced or widowed, a recent study from Singapore has found.
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01 Dec 2017
At a symposium during the 25th Congress of the Obstetrical and Gynaecological Society of Malaysia in Kuala Lumpur, Professor Susan Davis discussed the unique implications of women living decades beyond menopause, and how healthcare professionals can best manage menopausal symptoms in the short and long term.

Pyridoxine has little impact on capecitabine-induced hand-foot syndrome

Roshini Claire Anthony
08 Aug 2017

Pyridoxine does not reduce the incidence of grade ≥2 hand-foot syndrome in patients on capecitabine single-agent chemotherapy, according to a phase III trial conducted at the National Cancer Centre Singapore (NCCS).

Patients (n=210, median age 58 years, 77 percent female, 81 percent Chinese) receiving capecitabine as single agent therapy for any malignancy were randomized to receive daily doses of oral pyridoxine (200 mg) or placebo for a maximum eight capecitabine cycles. Breast and colorectal cancer were the primary cancer sites in most participants (66 and 29 percent, respectively).

The incidence of grade ≥2 hand-foot syndrome was comparable between patients given pyridoxine and placebo (31.4 percent vs 37.1 percent; p=0.38), with median time to onset not reached in patients in both groups, and no between-group difference (p=0.73). [JAMA Oncol 2017;doi:10.1001/jamaoncol.2017.1269]

Serum folate (odds ratio [OR], 1.30, 95 percent confidence interval [CI], 1.12–1.52 per 5 nmol/L increase; p<0.001) and red blood cell folate levels (OR, 1.28, 95 percent CI, 1.10–1.49 per 200 nmol/L increase; p=0.001) were independent predictors of an increased risk of developing grade ≥2 hand-foot syndrome.

Of 7,614,942 DNA variants determined from the study population, 300 were associated with grade ≥2 hand-foot syndrome at genome-wide significance (p <5 x 10-8), including a DPYD variant (rs75267292; p=1.57 x 10-10) and two SPRY2 variants involved in wound healing (rs117876855; p <1.01 x 10-8 and rs139544515; p=1.30 x 10-8).

“Genotyping is not routinely used in the clinical setting, so it is more for the generation of hypotheses in the pathophysiology of [hand-foot syndrome],” said lead investigator Dr Yap Yoon-Sim, a senior consultant oncologist at NCCS.

About half of Singaporean patients on capecitabine experience hand-foot syndrome, the symptoms of which are a reason for capecitabine dose reduction. Dose interruption or reduction, if necessary, is usually employed as treatment, as well as urea cream or emollients, and even analgesics if the pain is severe, said Yap.

According to the researchers, East Asians have demonstrated a lower risk of toxicity to fluoropyrimidines compared with their Caucasian counterparts, reflected in this study by the low occurrence of grade 3 or 4 diarrhoea, stomatitis, and neutropenia, although more than 30 percent of study participants had grade ≥2 hand-foot syndrome. This highlights the possibility that “the aetiology and predisposing factors for hand-foot syndrome” may differ from that of other capecitabine-related toxicities, they said, and called for studies into determining if these DNA variants can potentially predict a patient’s risk of hand-foot syndrome.

 

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Most Read Articles
11 Dec 2017
Combining the DASH (Dietary Approaches to Stop Hypertension) diet with low sodium intake reduces systolic blood pressure (SBP) in individuals with pre- and stage 1 hypertension, with progressively higher reductions at greater levels of baseline SBP, a recent study has shown.
Tristan Manalac, 5 days ago
Major depressive disorder (MDD) appears to be more prevalent in females than in males, particularly in those who are divorced or widowed, a recent study from Singapore has found.
6 days ago
Tadalafil may not be effective for reducing the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD), as shown in a recent study.
01 Dec 2017
At a symposium during the 25th Congress of the Obstetrical and Gynaecological Society of Malaysia in Kuala Lumpur, Professor Susan Davis discussed the unique implications of women living decades beyond menopause, and how healthcare professionals can best manage menopausal symptoms in the short and long term.