Page last updated: 2024-10-20

pteridines and Neutropenia

pteridines has been researched along with Neutropenia in 5 studies

Neutropenia: A decrease in the number of NEUTROPHILS found in the blood.

Research Excerpts

ExcerptRelevanceReference
"This study investigated the feasibility of predicting the neutropenia-related effects of a therapy that combines the investigational drug BI 2536 (inhibitor of Polo-like kinase 1) and pemetrexed, an approved anticancer drug."7.76Prediction of neutropenia-related effects of a new combination therapy with the anticancer drugs BI 2536 (a Plk1 inhibitor) and pemetrexed. ( Döge, C; Freiwald, M; Fritsch, H; Munzert, G; Soto, E; Staab, A; Trocóniz, IF, 2010)
"Neutropenia was described by a semi-mechanistic model resembling proliferation at the stem cell compartment, maturation, degradation, and homeostatic regulation."6.75Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development. ( Fritsch, H; Munzert, G; Soto, E; Staab, A; Tillmann, C; Trocóniz, IF; Trommeshauser, D, 2010)
"This study investigated the feasibility of predicting the neutropenia-related effects of a therapy that combines the investigational drug BI 2536 (inhibitor of Polo-like kinase 1) and pemetrexed, an approved anticancer drug."3.76Prediction of neutropenia-related effects of a new combination therapy with the anticancer drugs BI 2536 (a Plk1 inhibitor) and pemetrexed. ( Döge, C; Freiwald, M; Fritsch, H; Munzert, G; Soto, E; Staab, A; Trocóniz, IF, 2010)
"To determine the maximum tolerated dose (MTD) of volasertib, a Polo-like kinase inhibitor, combined with afatinib, an oral irreversible ErbB family blocker, in patients with advanced solid tumors (NCT01206816; Study 1230."2.80A phase I study of volasertib combined with afatinib, in advanced solid tumors. ( De Smet, M; Herremans, C; Liu, D; Machiels, JP; Peeters, M; Pilz, K; Rottey, S; Specenier, P; Strelkowa, N; Surmont, V, 2015)
"BI 2536 is a potent, highly selective inhibitor of polo-like kinase (Plk) 1."2.78A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer. ( Chu, QS; Ellis, PM; Fritsch, H; Gaschler-Markefski, B; Gyorffy, S; Laurie, SA; Leighl, N; Munzert, G, 2013)
"Neutropenia was described by a semi-mechanistic model resembling proliferation at the stem cell compartment, maturation, degradation, and homeostatic regulation."2.75Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development. ( Fritsch, H; Munzert, G; Soto, E; Staab, A; Tillmann, C; Trocóniz, IF; Trommeshauser, D, 2010)

Research

Studies (5)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's5 (100.00)24.3611
2020's0 (0.00)2.80

Authors

AuthorsStudies
Machiels, JP1
Peeters, M1
Herremans, C1
Surmont, V1
Specenier, P1
De Smet, M1
Pilz, K1
Strelkowa, N1
Liu, D1
Rottey, S1
Soto, E3
Staab, A3
Tillmann, C1
Trommeshauser, D1
Fritsch, H3
Munzert, G4
Trocóniz, IF3
Freiwald, M2
Döge, C1
Doege, C1
Ellis, PM1
Chu, QS1
Leighl, N1
Laurie, SA1
Gaschler-Markefski, B1
Gyorffy, S1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBW 2992 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit[NCT01206816]Phase 157 participants (Actual)Interventional2010-10-04Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Number of Participants With Dose Limiting Toxicities (DLT)

MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, <500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever >38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2. (NCT01206816)
Timeframe: 22 Days

Interventionparticipants (Number)
Volasertib150 mg+Afatinib 30 mg (Schedule A)0
Volasertib 225 mg+Afatinib 30 mg (Schedule A)0
Volasertib 300 mg+Afatinib 30 mg (Schedule A)3
Volasertib 300 mg+Afatinib 40 mg (Schedule A)2
Volasertib 300 mg+Afatinib 50 mg (Schedule B)0
Volasertib 300 mg+Afatinib 70 mg (Schedule B)5
Volasertib 300 mg+Afatinib 90 mg (Schedule B)2

Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0

Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0 (NCT01206816)
Timeframe: After the first drug administration until 28 days after the last drug administration, up to 413 days.

Interventionparticipants (Number)
Volasertib150 mg+Afatinib 30 mg (Schedule A)3
Volasertib 225 mg+Afatinib 30 mg (Schedule A)3
Volasertib 300 mg+Afatinib 30 mg (Schedule A)18
Volasertib 300 mg+Afatinib 40 mg (Schedule A)3
Volasertib 300 mg+Afatinib 50 mg (Schedule B)3
Volasertib 300 mg+Afatinib 70 mg (Schedule B)19
Volasertib 300 mg+Afatinib 90 mg (Schedule B)6

Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.

"Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The 3 + 3 design with de-escalation for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days." (NCT01206816)
Timeframe: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)

,
Interventionmg (Number)
VolasertibAfatinib
Volasertib in Combination With Afatinib (Schedule A)30030
Volasertib in Combination With Afatinib (Schedule B)30070

Number of Patients With Best Overall Response.

"Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response, partial response, stable disease, progressive disease or not evaluable.~As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive diseaseNot evaluableUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)000300
Volasertib 300 mg+Afatinib 30 mg (Schedule A)018812
Volasertib 300 mg+Afatinib 40 mg (Schedule A)000300
Volasertib 300 mg+Afatinib 50 mg (Schedule B)001200
Volasertib 300 mg+Afatinib 70 mg (Schedule B)0051004
Volasertib 300 mg+Afatinib 90 mg (Schedule B)002400
Volasertib150 mg+Afatinib 30 mg (Schedule A)010200

Number of Patients With Disease Control

"Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.~As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
YESNOUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)030
Volasertib 300 mg+Afatinib 30 mg (Schedule A)992
Volasertib 300 mg+Afatinib 40 mg (Schedule A)030
Volasertib 300 mg+Afatinib 50 mg (Schedule B)120
Volasertib 300 mg+Afatinib 70 mg (Schedule B)5104
Volasertib 300 mg+Afatinib 90 mg (Schedule B)240
Volasertib150 mg+Afatinib 30 mg (Schedule A)120

Number of Patients With Objective Response (OR)

"Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).~As Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions." (NCT01206816)
Timeframe: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

,,,,,,
Interventionparticipants (Number)
YesNoUnknown
Volasertib 225 mg+Afatinib 30 mg (Schedule A)030
Volasertib 300 mg+Afatinib 30 mg (Schedule A)1172
Volasertib 300 mg+Afatinib 40 mg (Schedule A)030
Volasertib 300 mg+Afatinib 50 mg (Schedule B)030
Volasertib 300 mg+Afatinib 70 mg (Schedule B)0154
Volasertib 300 mg+Afatinib 90 mg (Schedule B)060
Volasertib150 mg+Afatinib 30 mg (Schedule A)120

Trials

4 trials available for pteridines and Neutropenia

ArticleYear
A phase I study of volasertib combined with afatinib, in advanced solid tumors.
    Cancer chemotherapy and pharmacology, 2015, Volume: 76, Issue:4

    Topics: Administration, Oral; Adult; Afatinib; Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort

2015
Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development.
    Cancer chemotherapy and pharmacology, 2010, Volume: 66, Issue:4

    Topics: Algorithms; Cell Cycle Proteins; Chromatography, High Pressure Liquid; Data Interpretation, Statisti

2010
Comparison of different semi-mechanistic models for chemotherapy-related neutropenia: application to BI 2536 a Plk-1 inhibitor.
    Cancer chemotherapy and pharmacology, 2011, Volume: 68, Issue:6

    Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Cycle Proteins; Humans; Lung Neoplasms;

2011
A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer.
    Clinical lung cancer, 2013, Volume: 14, Issue:1

    Topics: Administration, Intravenous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma,

2013

Other Studies

1 other study available for pteridines and Neutropenia

ArticleYear
Prediction of neutropenia-related effects of a new combination therapy with the anticancer drugs BI 2536 (a Plk1 inhibitor) and pemetrexed.
    Clinical pharmacology and therapeutics, 2010, Volume: 88, Issue:5

    Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Smal

2010