Post hoc exploratory analysis of two phase 2 trials of quizartinib monotherapy in patients (pts) with FLT3-ITD–mutated (mu) relapsed/refractory (R/R) AML with or without prior 1st-generation FLT3 tyrosine kinase inhibitors (TKI) treatment.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7017-7017 ◽  
Author(s):  
Mark J. Levis ◽  
Catherine Choy Smith ◽  
Koji Ishizuka ◽  
Ken Kobayashi ◽  
Meena Arunachalam ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Exploratory Analysis ◽  
Phase 2 ◽  
Two Phase ◽  
Tki Treatment ◽  
Post Hoc

scholarly journals Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

2019 ◽  
Vol 12 (1) ◽  
pp. e226121 ◽  
Author(s):  
Tajwar Nasir ◽  
Claudia Lee ◽  
Alexandra SC Lawrence ◽  
Jeremy S Brown
Keyword(s):  
Tyrosine Kinase ◽  
Invasive Aspergillosis ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Case Series ◽  
High Dose ◽  
Effective Management ◽  
Traditional Risk Factors ◽  
Tki Treatment ◽  
Systemic Corticosteroid Therapy

We describe three cases of pulmonary aspergillosis (PA) in three patients without traditional risk factors for invasive aspergillosis infection, such as prolonged neutropenia or high dose systemic corticosteroid therapy. All three patients developed PA while taking tyrosine kinase inhibitors (TKI) and sustained greater clinical improvement once TKI were withdrawn. Our case series supports the theory TKI treatment can increase susceptibility to PA without causing neutropenia. Recognition that TKI treatment may predispose to invasive aspergillosis will allow for rapid recognition of affected patients and more effective management of future cases.

Risk of arterial thromboembolic events (ATEs) with tyrosine kinase inhibitors (TKIs) used in renal cell carcinoma: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13119-e13119
Author(s):  
Muhammad Zain Farooq ◽  
Jessey Mathew ◽  
Saad Malik ◽  
V V Pavan Kedar Mukthinuthalapati ◽  
Noureen Asghar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Thromboembolic Events ◽  
Phase 2 ◽  
Open Label ◽  
Increased Risk ◽  
Arterial Thromboembolic Events

e13119 Background: Tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of metastatic RCC and Sunitinib is approved for the use in adjuvant setting. Arterial thromboembolic events (ATEs) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence associated with the use of FDA approved TKIs used in treatment of RCC. Methods: PubMed, EMBASE, Cochrane Central and Scopus databases were searched to identify phase 2 and 3 RCTs of TKI therapy in RCC. Trials were included if they reported ATEs defined as arterial thrombosis, cerebral ischemia or infarction, myocardial ischemia and myocardial infarction. The DerSimonian-Laird random effects meta-analysis was performed using CMAv3 software to derive pooled estimates of incidence rates of ATEs with its 95% confidence interval (CI). I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: 1755 studies retrieved in the initial search, and 13 phase 2 and 3 clinical trials (n = 4983) were included in the quantitative analysis. The trials had open label design which can potentially result in bias. Risk of bias was low in all other domains. TKIs used for the treatment of RCC included sunitinib (n = 2632), sorafenib (n = 981), cabozantinib (n = 78), pazopanib (n = 844), axitinib (n = 189) and tivozanib (n = 259). The incidence of ATEs with the use of TKIs was 2.9% (95% CI: 2-3%). Cabozantinib was associated with the highest rate of ATEs (11.5%, 95% CI: 6-21%), followed by sunitinib (2.6%, 95% CI:2-3%) pazopanib (2.6%, 95% CI:2-4%) and axitinib (2.1%, 95% CI: 1-6%). The TKI with lowest event rate of ATE was tivozanib (0.8%, 95% CI:0.2-3%). Conclusions: The use of TKIs is associated with increased risk of developing ATEs. Clinicians should be aware of the possibility of increased ATEs and counsel the patients about this increased risk to enhance the process of informed decision making.

Hypogonadism in male cancer patients treated with the tyrosine kinase inhibitors sunitinib (SUN) or sorafenib (SOR)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3565-3565
Author(s):  
P. Wolter ◽  
H. Wildiers ◽  
D. Vanderschueren ◽  
H. Dumez ◽  
P. Clement ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Normal Range ◽  
Gonadal Dysfunction ◽  
Grade 3 ◽  
Tki Treatment

3565 Background: SUN and SOR are multi-targeted tyrosine kinase inhibitors (TKIs) inhibiting several kinases (VEGFR- 1,2; c-kit; PDGFR-α,β; flt-3; RET). SUN is approved for treatment of imatinib-resistant gastrointestinal stromal tumors (GIST) and metastatic renal cell carcinoma (RCC), SOR is used for RCC and hepatocellular carcinoma. We observed in some pts with fatigue under TKI treatment low testosterone (T) levels and started assessing the incidence and severity of gonadal dysfunction prospectively in male pts receiving these TKIs. Methods: Gonadal status (serum total testosterone (TT), free testosterone (FT), sex-hormone binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were evaluated in pts with RCC or GIST under SUN or SOR. SUN was given at a daily dose of 50 mg p.o. 4 weeks on, 2 weeks off, SOR at a daily oral dose of 800 mg. Results: We identified 27 pts (median age 63, range: 27–77), for which data on gonadal function were available, 23 RCC (85 %), 4 GIST (15%), with 22 (85.5%) receiving SUN and 5 (18.5%) SOR. Median treatment duration was 48 (2–202) weeks, 13 (48%) underwent dose reductions, in 4 (15%) pts due to grade 3 fatigue. All pts had at least once during TKI treatment T levels lower than normal (TT < 300 ng/dL and/or FT < 5 ng/dL), 17 (63%) had a low T with normal LH/FSH, 4 (15%) a low T with an elevated LH/FSH and 6 (22%) a low T and elevated FSH, but normal LH. The median TT level in the whole group was 194 ng/dL (21–477, normal range: 300–1,000 ng/dL), the median FT level in the whole group was 4.01 (0.45–9.07, normal range: 5–20 ng/dL). In the SUN cohort the median levels for TT and FT were slightly lower on day 28 in comparison to day 1 (184.5 vs 206 ng/dL for TT and 3.935 vs 4.225 ng/dl for FT). Pts with information available on testosterone at baseline (n = 8) tended to have slightly diminished baseline T levels (median: 222.5 [61–319] ng/dL), but 50% of these pts had been treated with other TKIs before. Two pts with grade 3 fatigue under SUN had very low T levels shortly after starting SUN (21 and 28 ng/dL, respectively). Conclusions: We observed a high incidence of hypogonadism in male RCC and GIST pts under treatment with SUN or SOR. Hypogonadism may likely contribute to the fatigue associated with these agents. [Table: see text]

scholarly journals Complete Remission With Tyrosine Kinase Inhibitors in Renal Cell Carcinoma

2012 ◽  
Vol 30 (5) ◽  
pp. 482-487 ◽  
Author(s):  
Laurence Albiges ◽  
Stéphane Oudard ◽  
Sylvie Negrier ◽  
Armelle Caty ◽  
Gwenaëlle Gravis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Complete Remission ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Local Treatment ◽  
Tki Treatment

Purpose Complete remission (CR) is uncommon during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs), but it may occur in some patients. It remains a matter of debate whether therapy should be continued after CR. Methods A multicenter, retrospective analysis of a series of patients with mRCC who obtained CR during treatment with TKIs (sunitinib or sorafenib), either alone or with local treatment (surgery, radiotherapy, or radiofrequency ablation), was performed. Results CR was identified in 64 patients; 36 patients had received TKI treatment alone and 28 had also received local treatment. Most patients had clear cell histology (60 of 64 patients), and all had undergone previous nephrectomy. The majority of patients were favorable or intermediate risk; however, three patients were poor risk. Most patients developed CR during sunitinib treatment (59 of 64 patients). Among the 36 patients who achieved CR with TKI alone, eight continued TKI treatment after CR, whereas 28 stopped treatment. Seventeen patients who stopped treatment (61%) are still in CR, with a median follow-up of 255 days. Among the 28 patients in CR after TKI plus local treatment, 25 patients stopped treatment, and 12 of these patients (48%) are still in CR, with a median follow-up of 322 days. Conclusion CR can occur after TKI treatment alone or when combined with local treatment. CR was observed at every metastatic site and in every prognostic group.

scholarly journals Patient Preferences for Stopping Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4274-4274
Author(s):  
Rachel MA Kyle ◽  
Alejandro Lazo-Langner ◽  
Anargyros Xenocostas ◽  
Ian H. Chin-Yee ◽  
Kang Howson-Jan ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Relapse Rate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Interquartile Range ◽  
Median Response ◽  
Tki Treatment

Abstract Abstract 4274 Introduction: After the introduction of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) became the first cancer with a medical treatment that affords patients a normal lifespan. First-line treatment includes one of the three approved TKIs with regular molecular monitoring. Several reports have described individuals stopping imatinib and remaining in complete molecular response (CMR). There are currently several ongoing randomized clinical trials evaluating the safety of stopping TKI treatment in patients with a sustained CMR. In 2010 the preliminary results from the STIM (STop IMatinib) trial (Mahon, Lancet Oncology), were published. Results showed that 38% of patients had a sustained CMR after 2 years off TKI treatment and the remaining 62% who relapsed responded to restarting their previous TKI treatment. As this research will potentially influence clinical practice in the near future, we aimed to explore patient reactions, preferences and risk acceptability of stopping TKI treatment. With that in mind we conducted an interview-assisted survey of CML patients seen at a single tertiary care centre. Methods: We included CML patients with cytogenetic and molecular Ph+ chromosome confirmation currently being treated with a TKI. Patients were approached during regular follow-up appointments. A survey was conducted through structured interviews using a standard form. Patients' preferences were explored through a case-based scenario using Visual Analog Scales ranging from 0 to 100% or 5-point Likert scales ranging from “absolutely stop” (1) to “absolutely not stop” (5). A trained interviewer asked the survey questions and was able to clarify questions that were unclear to the participant. Data was analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. 95% confidence intervals for the proportions were calculated using the normal approximation interval. Results: Interviews were conducted between June and August 2012 at the London Regional Cancer Program (LRCP) in London, Ontario. 38 out of 40 (95%) CML patients approached completed the survey. Mean age of participants was 51 years old and 47% were male. 37% of participants had not finished high school and another 37% had completed college/university/trade school. Participants had a diagnosis of CML for an average of 50 months prior to enrollment. The majority (21/38 participants, 55%) were taking imatinib, with 11 (29%) on nilotinib and 6 (16%) on dasatinib. 71% (95% CI ± 14%) of the participants said that taking their medications daily was “simple and easy and they were able to remember 100% of the time.” 26% reported daily side effects while 24% reported never experiencing side effects from their TKI. 79% (95% CI ± 13%) of the participants said that they have never considered stopping the drug based on the side effects that they experience. 61% of participants responded that fear of the disease going out of control keeps them taking their TKI (95% CI ± 16%), whereas 34% responded that it is their doctor's strong recommendation that motivates them (95% CI ± 15%). When asked what risk of relapse after stopping the TKI they would be willing to accept the median response was a 25% relapse rate (interquartile range 20–50). When responding to the same question after informing the participant that all patients have responded to restarting TKIs the median response increased to a 35% relapse rate (interquartile range 20–60). When given a relapse rate of 20% and a likert scale ranging from “absolutely stop” to “absolutely not stop,” the median response was “likely stop” with the 25th and 75th interquartile ranges being “absolutely stop” and “likely not stop” respectively. When the published relapse rate of 60% was given, however, the median was “likely not stop” with the 25th interquartile range at “neutral to stopping” and 75thinterquartile range at “absolutely not stop.” Discussion: This data suggests that the majority of participants perceive little difficulty with taking their TKI regularly and have never considered stopping it. Two major determinants on participant's decisions are fear of the disease going out of control and their physician's influence. Further, with the published rate of relapse after stopping TKI treatment the majority of individuals would choose to continue taking their medications for CML. Disclosures: Lazo-Langner: LeoPharma: Honoraria; Pfizer: Honoraria. Hsia:Novartis: Participant in Advisory Board Other.

Are tyrosine kinase inhibitors an effective treatment in testicular metastases from kidney cancer? Case report and review of the literature

2021 ◽  
pp. 030089162110592
Author(s):  
Fabio Turco ◽  
Marcello Tucci ◽  
Rosario Francesco Di Stefano ◽  
Alessandro Samuelly ◽  
Maristella Bungaro ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Target Therapy ◽  
Indirect Evidence ◽  
Cancer Case ◽  
Review Of The Literature ◽  
Testicular Lesions ◽  
Tki Treatment ◽  
Testicular Metastases

Testicular metastases from renal cell carcinoma (RCC) are extremely rare. Tyrosine kinase inhibitors (TKI) are the cornerstone of systemic therapy for metastatic RCC. We report a case of testicular metastasis in a 72-year-old patient with RCC that developed 17 years after nephrectomy and response to TKI treatment, a retrospective literature search on testicular metastases from RCC, and the indirect evidence described in the literature on the efficacy of chemotherapy and target therapy on testicular lesions.

Sign in / Sign up

Export Citation Format

Share Document