Heated (37 degrees C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy?

BACKGROUND/PURPOSE: Oxaliplatin-associated neuropathy remains a dose-limiting toxicity of the standard chemotherapy regimen of oxaliplatin and capecitabine for metastatic colorectal cancer. No preventive strategy has definitively been established. Because this neuropathy is triggered by cold, we hypothesized that infusing oxaliplatin at 37 degrees C might reduce neuropathy. METHODS: In this open-label pilot feasibility trial, patients with no prior chemotherapy for metastatic colorectal cancer were included. Treatment consisted of capecitabine 1,000 mg/m(2) bid on days 1-14 and oxaliplatin 130 mg/m2 on day 1 of a 21-day cycle. The oxaliplatin infusion was administered through a fluid-warming device at a constant temperature of 37 degrees C over 2 h. The primary endpoint was feasibility and drug reactions during the infusion. Secondary endpoints included acute and chronic neuropathy as well as response rate. RESULTS: Twenty patients were enrolled, and a total of 95 cycles administered. Median cumulative oxaliplatin dose was 735 mg/m(2). Apart from one patient with laryngeal spasm, no other infusion-related adverse events were observed. Of the patients, 35% reported grade 3/4 acute dysesthesia or paresthesia according to a patients questionnaire. Chronic neuropathy according to NCI CTC v3.0 was observed in 85% (grade 1) and 15% (grade 2), respectively. The overall response rate was 45% (95% CI 23-67%; 5% complete remission; 40% partial remission) and stable disease was achieved in another 30% of patients. CONCLUSION: Administration of heated oxaliplatin in combination with capecitabine is feasible and well tolerated without additional toxicity. While we have observed a relatively low rate of chronic cumulative neuropathy with heated oxaliplatin, this procedure appears not promising enough for us to recommend its further clinical evaluation.

High Risk of Hypophosphatemia in Patients with Previous Bariatric Surgery Receiving Ferric Carboxymaltose: A Prospective Cohort Study.

BACKGROUND: Iron deficiency is a common finding in patients with previous bariatric surgery, and parenteral supplementation is frequently required. Ferric carboxymaltose (FCM) is among the preferred compounds used but may be associated with new-onset hypophosphatemia. This study was undertaken to study the prevalence of hypophosphatemia following FCM in patients with previous bariatric surgery, a population that may be at particular risk due to highly prevalent secondary hyperparathyroidism. METHODS: Patients with previous bariatric surgery and iron depletion scheduled for FCM infusion were prospectively studied before and one week after FCM application. The primary endpoint was new-onset hypophosphatemia. Patients were followed until plasma phosphate had normalized without replacement. RESULTS: Fifty-two patients (40 females) following Roux-en-Y gastric bypass (n = 50) or sleeve gastrectomy (n = 2), with a median age of 46 years (range 22-68) and a BMI of 32.2 kg/m2 (27.5-37.3), were analyzed. Fifteen patients (29%) developed new-onset hypophosphatemia, with 11 (21%) requiring oral phosphate supplementation for a median duration of 14 days (14-25). The plasma phosphate decreased by 0.3 mmol/l (-0.5--0.2; p < 0.001) secondary to a 56% increase in the fractional urinary phosphate excretion (p < 0.001). This was associated with a significant increase in serum intact FGF23 (+30%; p < 0.001) and a decrease in serum 1,25(OH)2 vitamin D3 concentrations (-37.6%; p < 0.001). CONCLUSION: Patients with previous bariatric surgery receiving FCM are at considerable risk of developing significant hypophosphatemia secondary to increased renal phosphate wasting through a mechanism involving FGF23. Monitoring plasma phosphate should be considered following FCM in patients with previous bariatric surgery. CLINICAL TRIAL REGISTRATION: ISRCTN registry, ISRCTN12291677, https://www.isrctn.com.