Dose adjustment of cisplatin, etoposide, and ifosfamide according to kidney function: a retrospective analysis and implications for medication safety.

Clearance of cisplatin, etoposide, and ifosfamide depends on kidney function and dosages should be adjusted in patients with renal impairment. However, there is still limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment. Three thousand four hundred forty-eight prescriptions to 369 patients, treated in the Comprehensive Cancer Center of a German university hospital, were retrospectively evaluated. The administered relative doses of cisplatin, etoposide, and ifosfamide were compared with relative doses recommended at the time of prescription according to the patients' creatinine clearance. Cisplatin is contraindicated according to two German summary of product characteristics (SmPC) in patients with a creatinine clearance < 60 mL/min. Nevertheless, 37 cisplatin prescriptions were made for this group of patients (i.e., 2.0% of all cisplatin prescriptions). According to one German SmPC (valid in the year of data analysis), etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, while it is contraindicated below 15 mL/min. Thirteen etoposide prescriptions were without dose reduction in patients with creatinine clearance from 15 to 50 mL/min (1.5% of all etoposide prescriptions); one patient received etoposide with creatinine clearance below 15 mL/min. In 8.9% of ifosfamide prescriptions, patients did not receive a reduced dose in spite of respective recommendations. Dosages of cisplatin, etoposide, and ifosfamide are not always adjusted as recommended in patients with renal impairment. Consistent international dosing recommendations (e.g., in SmPCs), preferentially included in clinical decision support systems, should be developed to tackle this problem.

Antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting in palliative first-line treatment of colorectal cancer patients: the Northern Bavarian IVOPAK I Project.

PURPOSE: This study aims to evaluate adherence to guidelines of antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting (CINV) in the palliative first-line treatment of colorectal cancer (CRC) patients in Northern Bavaria. METHODS: We collected detailed information on chemotherapy and supportive drugs in 103 patients within a prospective observational study. The study was conducted to determine quality of care within an interdisciplinary context (first endpoint) and direct costs of palliative treatment for patients with CRC between 2006 and 2010 (second endpoint, Emmert et al. (Eur J Health Econ, 2012) [1]). In this paper, we evaluate adherence to Multinational Association of Supportive Care in Cancer (MASCC) 2006 recommendations for prophylaxis of CINV during the first administration of chemotherapy as well as incidence and grade of CINV within 120 h thereafter. RESULTS: Of the patients studied, 95 patients (92%) received moderately emetogenic (oxaliplatin- and/or irinotecan-containing combined chemotherapy treatment) and eight (8%) received low emetogenic chemotherapy (either 5-fluorouracil (5-FU) or capecitabine monotherapy). Antiemetic prophylaxis could be assessed in 101 out of 103 (98%) of patients. MASCC-recommended antiemetic prophylaxis was prescribed in three patients (3%). Nonadherence was mainly caused by omission of dexamethasone. Nausea and/or vomiting occurred in 18 patients (18%) within a 120-h period. All documented episodes were grade 1 or 2 according to the Common Toxicity Criteria of the National Cancer Institute. None of these patients received the recommended prophylaxis for CINV. In only one patient, antiemetic prophylaxis was intensified during the next chemotherapy application. CONCLUSIONS: In the Integrated Health Care in the Palliative Treatment of Colorectal Carcinoma (IVOPAK) I Project, adherence to the MASCC clinical recommendations was very poor. Extent of CINV in this patient population seems to be underestimated. There is an urgent need to improve clinicians' awareness of this patient-relevant side effect.