levoleucovorin and Nephrocalcinosis

Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Hypercalciuria; Irinotecan; Leucovorin; Magnesium; Male; Nephrocalcinosis; Prognosis; Renal Tubular Transport, Inborn Errors; Retrospective Studies; Survival Rate

The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrat-e-Rasoul Hospital in Tehran.. A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85 mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was 130 mg/m(2), every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms.. Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ≥ 25. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without.. Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.

Topics: Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Humans; Hypercalciuria; Iran; Leucovorin; Male; Middle Aged; Nephrocalcinosis; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Peripheral Nervous System Diseases; Renal Tubular Transport, Inborn Errors; Risk Factors