A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m(2) doxorubicin or equivalent were allowed. Left ventricular ejection fraction of > 50 % was required. Patients received PLD 50 mg/m(2) every 28 days or capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %;P = 0.31). Both PLD and capecitabine are effective first-line agents for MBC

Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2–1.0%. Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitorin

Immunochemotherapy - A Missed Opportunity for Metastasized Malignant Melanoma? Reporting a Therapeutic Success with Checkpoint Inhibitor Rechallenge after Cytotoxic Immuno-Priming in a Heavily Pretreated Patient

Treatment of metastasized malignant melanoma still has very limited therapeutic options. After exhaustion of immuno-checkpoint inhibition (ICI) and potentially targeted therapy, no promising alternatives are currently available. We report on an 83-year-old patient suffering from disseminated metastatic melanoma who showed an almost complete response to ICI following chemotherapy, after repeated failure of different regimens including two nonresponsive regimens of ICI. The presented outcome suggests a cytotoxic immuno-priming, facilitating a response to prior nonresponsive ICI. As this concept has not been established until now for malignant melanoma, in contrast to multiple other cancer entities, our case report corroborates previous evidence and therefore suggests a new treatment option, which should be researched further

Blasenkarzinom (Urothelkarzinom)

Das Harnblasenkarzinom gehört zu den häufigen malignen Tumoren. Männer sind dreimal öfter als Frauen betroffen, das mittlere Erkrankungsalter liegt bei über 70 Jahren. Urothelkarzinome machen über 90% aller Blasenkarzinome aus. Die häufigste Manifestationsform ist das oberflächliche, nicht muskelinvasive Urothelkarzinom. Risiken sind lokale Rezidive und die Entwicklung eines höheren Stadiums. Beim muskelinvasiven Blasenkarzinom ist die Behandlung multimodal mit optimaler, patienten-orientierter Zystektomie und der Option einer frühen Chemotherapie. Bei metastasierter Erkrankung ist eine medikamentöse Tumortherapie indiziert. Zum bisherigen Standard der zytostatischen Behandlung kommen aktuell die Optionen einer Immuntherapie mit Checkpoint-Inhibitoren. Nicht-urotheliale Blasenkarzinome sind nicht Gegenstand dieser Leitlinie

Herpes Zoster Vaccination Rates in Hematological and Oncological Patients—Stock Taking 2 Years after Market Approval

Background: Vaccinations have the potential to significantly lower the burden of disease for many major infections in the high-risk population of hematological and oncological patients. In this regard Shingrix®, an inactivated Varicella Zoster Virus vaccine, received market approval in the European Union in March 2018, after prior US approval in October 2017, and recommendations specifically state immunocompromised, including oncological, patients. As vaccination rates are considered to be poor in oncological patients, determining the current vaccination rates for Shingrix® two years after market approval is important in defining the need for intervention to bring this potentially high-impact vaccine to the patients. Methods: We analyzed data of the EVO Study to provide data for Herpes zoster vaccination rates in oncological patients. The EVO Study was an interventional study evaluating the potential of increasing vaccination rates of specified must-have vaccinations by an instructional card in the oncological setting. Numbers presented in this publication merged baseline data and follow-up data of the control group; hence data not affected by the intervention. Results: Data of 370 patients were analyzed; 21.1% with hematological malignancies and 78.9% with solid cancer. Only 3.0% were vaccinated with Shingrix®. Patients with hematological malignancy were more likely to be vaccinated than those with solid cancer (7.7 vs. 1.7%). Conclusion: Despite clear recommendations and a pressing need in the high-risk population of hematological and oncological patients, the vast majority of patients are still left without vaccine protection against Herpes zoster by Shingrix®