Effectiveness of a vitamin D regimen in deficient multiple myeloma patients and its effect on peripheral neuropathy.

PURPOSE: Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D3 supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D3 regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D3 supplementation on PN. METHODS: Thirty-nine MM patients with inadequate (< 75 nmol/L [= 30 ng/mL]) 25-hydroxyvitamin D (25(OH)D) levels were included in this multicenter, prospective, single-arm study, of whom 35 patients completed the study. They received oral vitamin D3 for 6 months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200 IU/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN. RESULTS: Median 25(OH)D increased from 38 (IQR 32-52) nmol/L at baseline to 77 (IQR 72-87) nmol/L after 6 months (P < 0.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50-75 nmol/L. Furthermore, in 37% of the participants, PN severity decreased (P = 0.007). CONCLUSION: The use of substantially higher vitamin D3 doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research.

Clinical implications of food-drug interactions with small-molecule kinase inhibitors.

During the past two decades, small-molecule kinase inhibitors have proven to be valuable in the treatment of solid and haematological tumours. However, because of their oral administration, the intrapatient and interpatient exposure to small-molecule kinase inhibitors (SMKIs) is highly variable and is affected by many factors, such as concomitant use of food and herbs. Food-drug interactions are capable of altering the systemic bioavailability and pharmacokinetics of these drugs. The most important mechanisms underlying food-drug interactions are gastrointestinal drug absorption and hepatic metabolism through cytochrome P450 isoenzymes. As food-drug interactions can lead to therapy failure or severe toxicity, knowledge of these interactions is essential. This Review provides a comprehensive overview of published studies involving food-drug interactions and herb-drug interactions for all registered SMKIs up to Oct 1, 2019. We critically discuss US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines concerning food-drug interactions and offer clear recommendations for their management in clinical practice.

Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. Although the HIPEC procedure is adopted throughout the world, major differences exist between treatment protocols regarding the carrier solution, perfusate volume, use of an open or closed technique, duration of the perfusion and application of additional flushing. These differences can influence the pharmacokinetics and pharmacodynamics of oxaliplatin and might thereby have an impact on the efficacy and/or safety of the treatment. Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure.

Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific populations of patients with type 2 diabetes. The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 6-month double-blind study, patients with an HbA(1c) (A1C) >8% and insulin requirements of >50 units/day were randomly assigned to receive treatment with placebo or 500 or 1,000 mug chromium daily in the form of chromium picolinate. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, and insulin requirements. RESULTS: In this per-protocol analysis (n = 46), the decrease in A1C was approximately equal across the three groups (0.4%). All patients had a BMI >25 kg/m(2). No differences were found in the secondary end points. We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile. CONCLUSIONS: There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes.

Cost-benefit analysis of capecitabine versus 5-fluorouracil/leucovorin in the treatment of colorectal cancer in the Netherlands.

BACKGROUND: Capecitabine is an oral prodrug of 5-fluorouracil and has been studied for the treatment of colorectal cancer. In 2 Phase III trials, capecitabine was at least as effective as 5-fluorouracil plus leucovorin and had a more favorable toxicity profile. OBJECTIVE: A cost-benefit analysis was used to assess the pharmacoeconomic profile of capecitabine compared with 5-fluorouracil/leucovorin, given according to the Mayo regimen, for colorectal cancer patients treated in the Netherlands. METHODS: The medical files of patients treated for colorectal cancer at a single center from 1999 to 2002 were examined to determine the numbers of outpatient visits for 5-fluorouracil/leucovorin administration, health care use and medication to manage adverse effects, and travel distance to and from the hospital. The costs of capecitabine treatment were simulated by assuming that the same patients were treated with capecitabine instead of 5-fluorouracil/leucovorin. Toxicity data for capecitabine were derived from 2 Phase III studies that compared capecitabine and 5-fluorouracil/leucovorin. RESULTS: The files of 65 patients were reviewed. Thirty-two patients received adjuvant treatment and 33 patients were treated palliatively for metastatic disease. The mean total costs of palliative treatment were Euro 4004 with capecitabine and Euro 5614 with 5-fluorouracil/leucovorin. These results were robust in sensitivity analyses. The cost savings were primarily related to the number of outpatient visits for capecitabine versus the number of day-care treatment days for 5-fluorouracil/leucovorin, despite the higher acquisition costs of capecitabine. CONCLUSIONS: Based on this analysis, treatment of colorectal cancer with oral capecitabine is cost saving in the Netherlands compared with 5-fluorouracil plus leucovorin administered according to the Mayo regimen. Baseline savings were estimated at Euro 1610 for palliative treatment and Euro 934 for adjuvant treatment.