There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patien... more There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication. Two phase I pharmacokinetic and safety studies of i.v. oseltamivir were carried out in healthy volunteers. The first was an open-label, randomized, four-period, two-sequence, single-dose trial of 100 mg, 200 mg, and 400 mg oseltamivir i.v. over 2 h and a 75-mg oral dose of oseltamivir. The second was a double-blind, placebo-controlled, parallel-group, multiple-dose study in which participants were randomized to 100 mg or 200 mg oseltamivir or placebo (normal saline) i.v. over 2 h every 12 h for 5 days. Exposure to the active metabolite oseltamivir carboxylate (OC) after dosing achieved with 100 mg oseltamivir administered i.v. over 2 h was comparable to that achieved with 75 mg administered orally. Single i.v. doses of oseltamivir up to 400 mg were well tolerated with no new safety signals. Multiple-dose data confirmed good tolera...
Background: Antiangiogenic therapy is routinely used in a variety of cancer entities. Hypertensio... more Background: Antiangiogenic therapy is routinely used in a variety of cancer entities. Hypertension is the most common side effect of all currently available antiangiogenic treatments. Patients and Methods: In this prospective observational clinical trial, we investigated risk factors for blood pressure elevation in patients exposed to an antiangiogenic agent and explored the correlation between hypertension and the duration of antiangiogenic treatment. Results: In 169 patients, pre-existing antihypertensive medication was the most prominent risk factor associated with increased blood pressure during therapy. Between visits 1 and 3, the median systolic blood pressure increased by 10.85 mmHg in patients with pre-existing hypertension receiving antihypertensive medication while it increased by only 2.69 mmHg in patients without hypertension. The median increase in diastolic pressure was 7.28 versus 0.11 mmHg in patients with versus without pre-existing hypertension. Increases in blood pressure occurred early (within 6 weeks of starting therapy). In spite of this significant increase in the blood pressure, no major bleeding events or other related complications were observed during antiangiogenic therapy. Conclusions: Pre-existing hypertension and treatment with antihypertensive medication correlated with a more pronounced increase in blood pressure. Thus, intensified antihypertensive therapy might be warranted early during bevacizumab therapy in patients already receiving antihypertensive treatment.
Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to... more Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia...
Purpose: These are the final results of a national registry on cancer patients with COVID-19 in S... more Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. Results: From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus <65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p < 0.001) and oxygen requirement (OR 20.28, p < 0.001) were indepe...
Objective CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibit... more Objective CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC504.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B). Design and methods (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B). Results DC24 was attained in 5/21 (95% CI: 8.2–47.2) patients in (A) and none in (B). The media...
BACKGROUND International guidelines state that bone-targeted agents such as denosumab or zoledron... more BACKGROUND International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. METHODS To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-spe...
Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (... more Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99...
SummaryPurpose BAL101553, the prodrug of the microtubule-destabilizer BAL27862, previously showed... more SummaryPurpose BAL101553, the prodrug of the microtubule-destabilizer BAL27862, previously showed signs of antitumor activity when administered as a 2-h infusion, but its use was limited by vascular toxicity. We investigated an alternative dosing strategy aimed at improving the safety profile of BAL101553. Methods This multicenter, open-label, Phase 1 dose-escalation study used a 3 + 3 design to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and antitumor activity of BAL101553 administered as a 48-h IV infusion on Days 1, 8, and 15 of a 28-day cycle. Patients received oral BAL101553 on Days 15–21 of cycle 2 to assess oral bioavailability. Results BAL101553 was well tolerated at doses up to ≤70 mg/m2. Three grade 3 DLTs occurred: hypotension (70 mg/m2), hyponatremia and neutropenia (both 90 mg/m2). The MTD for 48-h IV BAL101553 was 70 mg/m2. At this dose level, the AUC for BAL27862 was 8580 ng.h/mL and the Cmax was 144 ng/mL. No apparen...
There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patien... more There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication. Two phase I pharmacokinetic and safety studies of i.v. oseltamivir were carried out in healthy volunteers. The first was an open-label, randomized, four-period, two-sequence, single-dose trial of 100 mg, 200 mg, and 400 mg oseltamivir i.v. over 2 h and a 75-mg oral dose of oseltamivir. The second was a double-blind, placebo-controlled, parallel-group, multiple-dose study in which participants were randomized to 100 mg or 200 mg oseltamivir or placebo (normal saline) i.v. over 2 h every 12 h for 5 days. Exposure to the active metabolite oseltamivir carboxylate (OC) after dosing achieved with 100 mg oseltamivir administered i.v. over 2 h was comparable to that achieved with 75 mg administered orally. Single i.v. doses of oseltamivir up to 400 mg were well tolerated with no new safety signals. Multiple-dose data confirmed good tolera...
Background: Antiangiogenic therapy is routinely used in a variety of cancer entities. Hypertensio... more Background: Antiangiogenic therapy is routinely used in a variety of cancer entities. Hypertension is the most common side effect of all currently available antiangiogenic treatments. Patients and Methods: In this prospective observational clinical trial, we investigated risk factors for blood pressure elevation in patients exposed to an antiangiogenic agent and explored the correlation between hypertension and the duration of antiangiogenic treatment. Results: In 169 patients, pre-existing antihypertensive medication was the most prominent risk factor associated with increased blood pressure during therapy. Between visits 1 and 3, the median systolic blood pressure increased by 10.85 mmHg in patients with pre-existing hypertension receiving antihypertensive medication while it increased by only 2.69 mmHg in patients without hypertension. The median increase in diastolic pressure was 7.28 versus 0.11 mmHg in patients with versus without pre-existing hypertension. Increases in blood pressure occurred early (within 6 weeks of starting therapy). In spite of this significant increase in the blood pressure, no major bleeding events or other related complications were observed during antiangiogenic therapy. Conclusions: Pre-existing hypertension and treatment with antihypertensive medication correlated with a more pronounced increase in blood pressure. Thus, intensified antihypertensive therapy might be warranted early during bevacizumab therapy in patients already receiving antihypertensive treatment.
Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to... more Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia...
Purpose: These are the final results of a national registry on cancer patients with COVID-19 in S... more Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. Results: From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus <65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p < 0.001) and oxygen requirement (OR 20.28, p < 0.001) were indepe...
Objective CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibit... more Objective CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC504.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B). Design and methods (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B). Results DC24 was attained in 5/21 (95% CI: 8.2–47.2) patients in (A) and none in (B). The media...
BACKGROUND International guidelines state that bone-targeted agents such as denosumab or zoledron... more BACKGROUND International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. METHODS To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-spe...
Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (... more Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99...
SummaryPurpose BAL101553, the prodrug of the microtubule-destabilizer BAL27862, previously showed... more SummaryPurpose BAL101553, the prodrug of the microtubule-destabilizer BAL27862, previously showed signs of antitumor activity when administered as a 2-h infusion, but its use was limited by vascular toxicity. We investigated an alternative dosing strategy aimed at improving the safety profile of BAL101553. Methods This multicenter, open-label, Phase 1 dose-escalation study used a 3 + 3 design to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and antitumor activity of BAL101553 administered as a 48-h IV infusion on Days 1, 8, and 15 of a 28-day cycle. Patients received oral BAL101553 on Days 15–21 of cycle 2 to assess oral bioavailability. Results BAL101553 was well tolerated at doses up to ≤70 mg/m2. Three grade 3 DLTs occurred: hypotension (70 mg/m2), hyponatremia and neutropenia (both 90 mg/m2). The MTD for 48-h IV BAL101553 was 70 mg/m2. At this dose level, the AUC for BAL27862 was 8580 ng.h/mL and the Cmax was 144 ng/mL. No apparen...
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Papers by Roger Von Moos