Comparative Cost Analysis Of Intravenous And Subcutaneous Administration Of Rituximab In Lymphoma Patients.

PURPOSE: The availability of different routes of administration of rituximab, with different dosing and times of infusion in the day care unit, raises the question of which formulation would be the best in terms of direct cost, particularly with the approval of new intravenous (IV) rituximab biosimilars. We aim to retrospectively compare the direct costs of IV and subcutaneous (SC) rituximab in lymphoma, considering drug cost, pharmacy handling and occupation in day care unit in Son Espases University Hospital during 2017, now that the IV biosimilar is available. PATIENTS AND METHODS: The data were collected from Oncosafety®-AVIDA for doses and SAP® for economic data. The costs of occupation are published by the Local Health Service. RESULTS: In 2017, 527 cycles were prescribed for 103 patients with lymphoma: 141 IV and 386 SC. Median doses were 690 mg and 1400 mg with a median cost of the drug of 1458.45€ and 1334.77€ for IV and SC routes, respectively. The nurse handling costs were 4.49€ and 2.24€, respectively. The cost of the day care unit occupation was 493€ and 123€, respectively. Overall, the median total cost per cycle was 1955.94€ for the IV, 1460.01€ for the SC and 1729€ for the biosimilar (p<0.001). The sensitivity analysis showed that it would be necessary for the cost of the IV biosimilar to be 34% lower than the price of SC rituximab to make a difference. CONCLUSION: This study shows a reduction in the cost with the administration of SC rituximab in real life compared with using the IV original rituximab and the biosimilar. This information is relevant for healthcare managers and administrations and applies only in the case of drugs with SC original presentations still not available in their correspondent biosimilars.

2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.

BACKGROUND: High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods. OBJECTIVE: To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2. METHODS: Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS). RESULTS: The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal. CONCLUSION: DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.

Differential Impact of Relative Dose-Intensity Reductions in Diffuse Large B-Cell Lymphoma Treated with R-CHOP21 or R-CHOP14.

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.

Efficacy of taxanes as adjuvant treatment of breast cancer: a review and meta-analysis of randomised clinical trials.

OBJECTIVES: To evaluate the magnitude of benefit obtained by taxanes as adjuvant treatment of breast cancer and to assess the best method for their administration. MATERIAL AND METHODS: We performed a systematic search of phase III randomised clinical trials that included patients with non-metastatic breast cancer in whom comparisons were chemotherapy (CT) containing a taxane (docetaxel or paclitaxel) vs. CT without taxanes (first-generation trials), or CT with taxane in both treatment arms (second-generation trials), administered after surgery. The parameters of efficacy evaluated were disease-free survival (DFS) and overall survival (OS). The data obtained in the first-generation trials (number of relapses and deaths) were submitted to a meta-analysis. The odds ratio (OR) combined with DerSimonian and Laird (OR DL) and 95% confidence interval (95% CI) were calculated. Further, an analysis was performed of those trials that included only patients with nodal involvement (N+). In both cases, the results were also analysed as a function of the taxane used, and with indirect comparisons between the two. The second-generation trials were analysed to assess the optimum method of administration. RESULTS: A total of 17 trials were selected for the meta-analysis (30,672 patients). The OR DL was 0.82 (95%CI: 0.76-0.88) for DFS and 0.83 (95% CI: 0.75-0.91) for OS. In N+ patients the results were 0.80 (95% CI: 0.74-0.86) and 0.79 (95% CI: 0.69-0.89), respectively. Docetaxel and paclitaxel significantly increased the DFS and OS. In our indirect comparison, the benefit of docetaxel on OS was significantly superior to that obtained with paclitaxel in N+ patients (OR: 0.79; 95% CI: 0.63-0.98). CONCLUSIONS: The administration of adjuvant CT-based taxanes reduces the risk of relapse and death. This reduction is superior in clinical trials that included only N+ patients. With the available evidence, it would appear that the best method of administering paclitaxel is weekly and for docetaxel tri-weekly.