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Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among cancer patients. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in ovarian cancer patients. We measured NFL in medium from human induced pluripotent stem-cell derived sensory neurons (iPSC-SNs) treated with paclitaxel. Serum NFL (sNFL) levels were quantified in 190 ovarian cancer patients receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. PIPN-related adverse outcomes were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients that discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner (P0.001, ANOVA). sNFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 (95% CI 1.16-5.22), adjusted HR: 2.25 (95% CI: 0.88-5.79)). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction due to PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). NFL constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, sNFL can be utilized to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.

A 24-year-old woman with asthma presented with symptoms of upper airway infection and tachypnoea and wheezes. She had a history of admissions to intensive care units (ICU) due to respiratory insufficiency. The initial lactate concentration was 2.1 mmol/l. The treatment consisted of inhaled and intravenous β ² agonists. Hereafter, the lactate concentration rose to 9.8 mmol/l, and the patient was admitted to the ICU due to severe asthma exacerbation. The elevation of lactate concentration cleared after discontinuation of β ² agonist therapy. Although lactic acidosis is a rare side effect to β ² agonist treatment, it is important to recog-nize it when present.

e-Cigarettes have gained worldwide popularity as a substitute for smoking, but concern has been raised regarding the long-term effects associated with their use. We report a case of a 45-year-old female consumer of e-cigarettes who presented with 4 months of abdominal pain and fever. Initial imaging discovered multiple pulmonary nodules and liver lesions suspicious of widespread metastases; however, an extensive evaluation found no evidence of malignancy. Results of a lung biopsy revealed an area with multinucleated giant cells suggestive of a foreign body reaction to a lipophilic material. Upon cessation of e-cigarette use (known as vaping), the lung nodules disappeared, and the liver lesions regressed. Our case report suggests that vaping can induce an inflammatory reaction mimicking metastatic cancer.

Kittelhåndbog for onkologer og hæmatologer i DK Håndteringen af lægemiddelinteraktioner i klinisk praksis er vanskelig. Patienternes kliniske udtryk er præget af broget mangfoldighed og evidensniveauet for flertallet af interaktioner begrænser sig ofte til kasuistikker eller enkelte små interaktionsstudier. I praksis overlades det til klinikeren at undersøge og afgøre for hvert enkelt tilfælde hvorvidt lægemiddelinteraktion kan have betydning. Dette stiller store krav til klinikere i almindelighed og til hæmatologer og onkologer i særdeleshed pga disses tiltagende brug af polyfarmaci og komplicerede behandlingsregimer med snævre terapeutiske intervaller.Lægemiddelinteraktion mellem antineoplastisk virkende lægemidler og ikke antineoplastisk virkende lægemidler gennemgås efter systematisk udvælgelse. Kilder: http://www.interaktionsdatabasen.dk/ der drives af Lægemiddelstyrelsen, Swedish Finnish Interaction X-referencing (SFINX) (http://www.janusinfo.se/) der drives af Läkemedelscentrum i Stockholm läns landsting, Stockleys Drug Interactions (8.udg, 2008 -Pharmaceutical Press, ed.:K.Baxter), www.Medicin.dk , Produktresumeer (SPC) og PubMed.Resultat: 190 interaktionsmonografier fordelt på 51 af ialt 67 antineoplastisk virkende stoffer. Monografierne er uden klinisk vejledning. Der opgives en enkelt reference til originalkilde.

Når lokalbehandling til candidainfektion ikke er nok, er næste valg systemisk behandling. Men hvad, hvis kvinden ammer? Kan systemisk behandling med tablet fluconazol anvendes? Svaret er ja – men langvarig behandling (> 2 uger) bør undgås. Fluconazol vil udskilles i brystmælk, men mængden af fluconazol, som barnet derved indtager, er lav.

I denne artikel præsenteres en sygehistorie, hvor en ældre kvinde får tiltagende konfusion og psykotiske symptomer en uge efter seponering af højdosis-tramadol og skift til Contalgin. Disse mulige seponeringssymptomer kan skyldes abrupt ophør af tramadols serotonerge effekt, og forfatterne konkluderer, at man må have skærpet opmærksomhed på atypiske bivirkninger i forbindelse med seponeringaf især langvarig/høj-dosering af tramadol, særligt hvis symptomerne ikke umiddelbart svinder ved morfinsubstitution.

Lægemiddelinformationen ved Odense Universitetshospital hjælper med svar på spørgsmål fra den kliniske hverdag i almen praksis. Vi begynder med spørgsmål omkininbehandling til natlige lægkramper. Er det indiceret, og er der kontraindikationer? Artiklen påpeger også, at natlige lægkramper og restless legssyndrome er to forskellige tilstande, der skal behandles forskelligt

BackgroundToxicity and therapeutic effects of paclitaxel vary greatly between patients and remain a clinically relevant problem with regard to the handling of dose delay/reduction or termination of treatment. We investigated the notion that single nucleotide polymorphisms (SNPs) in CYP2C8 could be partly responsible for this variation. Paclitaxel is mainly metabolized by CYP2C8; SNPs have been investigated in this context before but conclusions are still lacking. We present a prospective study of paclitaxel clearance (CL) in 93 Caucasian females with epithelial ovarian cancer with regard to the CYP2C8 *1b, *1c, *3 and *4 genotypes.Material and methodsAll patients were diagnosed with primary ovarian/peritoneal cancer and received 175mg/m2 paclitaxel over 3 hrs plus carboplatin (AUC5-6) q3w. All patients gave written and verbal consent. The study was approved by ethics committees in Denmark and Sweden. Blood was sampled at 3hrs, 5-8 hrs and 18-24hrs after start of infusion. Total plasma paclitaxel was quantified using HPLC. CremophorEL® (CrEL) was determined as described by Sparreboom et al.1998. CL of unbound paclitaxel was estimated using total concentrations, CrEL and other parameters in the model described by Henningsson et al.2003 using NONMEM VI. Genotypes were determined using Pyrosequencing. Genotypes were in HW equilibrium, except *1b (p=0.01).ResultsThe PK model predicted the data well. The CL of unbound paclitaxel was lower for patients with the CYP2C8*3 and *4 variants (pCYP2C8variantNPaclitaxel CL geometric mean (l/h)95% c.iP-value(T-test of log transformed CL)Wt/Wt49395.0[370.3;421.4] Wt/*1b + *1b/*1b(n=1)44374.5[348.8;402.2]0.267Wt/Wt69382.4[362.1;404.0] Wt/*1c24393.1[355.4;434.8]0.617Wt/Wt74394.7[375.2;415.3] Wt/*319350.0[310.0;395.3]0.041*Wt/Wt86390.9[372.1;410.7] Wt/*47320.8[281.7;365.3]0.028*Note: for the one patient carrying both the *3 and *4 variant CL was 269.7 l/hConclusionsThis study implies reduced elimination of paclitaxel in Caucasian female patients with the CYP2C8*3 and *4 genotypes. This confirms several in vitro studies and pilot studies but is different to Henningsson et al 2005 and Marsh et al 2006 which could be explained by differences in dose ranges, infusion times and/or related to gender. The finding is important in terms of understanding inter individual variability of paclitaxel pharmacokinetics and might in the future provide useful information for individualized chemotherapy.