Beyond the bevacizumab resistance, combined effects of erlotinib in heavily pretreated patients with recurrent ovarian cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16505-e16505
Author(s):  
Yoshihiro Kikuchi ◽  
Masashi Takano ◽  
Yuji Ikeda ◽  
Ryoko Kikuchi ◽  
Kazuya Kudoh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Solid Tumors ◽  
Synergistic Effects ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cytotoxic Agents ◽  
Ovarian Cancers ◽  
Heavily Pretreated ◽  
Pretreated Patients

e16505 Background: In heavily pretreated ovarian cancer patients, bevacizumab (B) combined with conventional chemotherapy has been reported to improve the response. However, responses to B are usually transient and resistance inevitably develops. The vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) are valid targets in many solid tumors, and their inhibitors have synergistic effects in preclinical studies. Methods: In 13 patients with heavily pretreated ovarian cancers, after development of B resistance erlotinib (E) (150 mg/day, 3 week, one week rest) and B (2 mg/kg/week, 3 week, one week rest) were administered with cytotoxic agents until development of disease progression or unmanageable adverse effects (AE). The primary endpoint in this study was response rate (RR) and progression-free survival (PFS). Results: Of 13 patients, 3 patients were not evaluable for response evaluation criteria in solid tumors (RECIST). Of 10 patients, 3 (30%) patients had partial responses (PR), 4 (40%) had stable diseases (SD), resulting in 70% clinical benefit rate (CBR). The PFS lasts more than 6 months in 4 (40%) patients. Although main AEs by E were rash, diarrhea and mucositis, all cases were manageable and tolerable. Conclusions: E administration after development of B resistance can reverse effects of B in 70% of heavily pretreated patients with recurrent ovarian cancers. AE of E was manageable and tolerable. These results warrant further studies in such clinical settings.

Effects of weekly bevacizumab and pegylated liposomal doxorubicin in heavily pretreated patients with recurrent or progressed ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5547-5547
Author(s):  
Y. Kikuchi ◽  
H. Kouta ◽  
R. Kikuchi ◽  
M. Takano ◽  
T. Kita ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Treatment Options ◽  
Evaluation Criteria ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Cytotoxic Agents ◽  
Ca 125 ◽  
Heavily Pretreated ◽  
Pretreated Patients

5547 Background: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded a promising therapeutic target. Bevacizumab (A) has significant antitumor activity in combination with cytotoxic agents. Currently, pegylated liposomal doxorubicin (D) is provided as one of the standard treatment options in recurrent ovarian cancer. Thus, we attempted to determine effects in combination of A and D for heavily pretreated patients with recurrent or progressed ovarian cancer. Methods: Twenty-two patients with heavily pretreated (more than one regimen or more than 6 cycles by paclitaxerl and carboplatin) received at least more than 3 cycles of weekly A-D consisting of A: 2 mg/kg and D: 10 mg/m2 (3 weeks, one week rest). The primary endpoint was response according to CA 125 and response evaluation criteria in solid tumor (RECIST) criteria. Results: Of 22 patients evaluable for CA 125 response, 7 (32%) had a response (decrease of >50%), and 8 (36%) patients had not progressed (doubling of CA 125) following 6 months on treatment. In RECIST evaluation, 2 (9%) patients had complete remission (CR) and 6 (27%) had partial remission (PR), resulting in 55% clinical benefit rate (CBR). Progression free interval (PFI) showed more than 6 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in only one case and was conservatively treated. Although nasal bleeding was frequently observed, no treatment was required. A induced hypertension was also observed and manageable. Hand-foot syndrome seemed due to D was seen in 3 of 22 patients and treatment was required in only one case. Conclusions: B seemed to enhance effect of D. This is the first study of weekly A-D in heavily pretreated ovarian cancer patients. Weekly A-D warrants further clinical study in such clinical settings. No significant financial relationships to disclose.

Retreatment of Irinotecan in Later Lines of Therapy for Metastatic Colorectal Cancer: A Retrospective Study

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Moon Ki Choi ◽  
Yongjun Cha ◽  
Ji Yeon Baek
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Epidermal Growth ◽  
Grade 3

<b><i>Background:</i></b> Due to few efficacious options in later lines of therapy in metastatic colorectal cancer (mCRC), there has been considerable interest in the possibility of retreatment with previously administered agents. This study investigated the efficacy and safety of irinotecan retreatment (IRI2) in patients with refractory mCRC. <b><i>Methods:</i></b> We performed a retrospective analysis of patients with mCRC who were retreated with irinotecan-based regimens. The retreatment regimens with anti-epidermal growth factor receptor therapies were excluded. <b><i>Results:</i></b> A total of 64 patients were included. Patients had a median age of 56 years and were offered mainly in the setting of third- or fourth-line therapy with IRI2. The disease control rate was 78.2% including an objective response of 23.5%. Median progression-free survival and overall survival were 5.5 and 19.3 months, respectively. The most frequent grade 3 or higher toxicities were nausea/vomiting (27.9%) and neutropenia (25%). <b><i>Conclusion:</i></b> IRI2 might be a reasonable option for heavily pretreated patients with mCRC who achieved disease control with prior irinotecan therapy.

scholarly journals Frequency and Prognosis of Epidermal Growth Factor Receptor Variant III Mutations in Glioblastoma Multiforme among Indian Patients: A Single-Institution Study

2020 ◽  
Vol 09 (03) ◽  
pp. 126-129
Author(s):  
Wesley Mannirathil Jose ◽  
Vinayak Munirathnam ◽  
V. Narendranath ◽  
Arun Philip ◽  
Pavithran Keechilat
Keyword(s):  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Epidermal Growth Factor ◽  
World Literature ◽  
Mutational Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Cancer Center ◽  
Epidermal Growth

Abstract Background Glioblastoma multiforme (GBM) is a disease with poor outcome. Alterations or mutations in epidermal growth factor receptors (EGFRs) are found in GBM and may be targeted to improve outcomes. Aims We analyzed the frequency of EGFR variant III (vIII) mutations in patients with GBM and their outcomes after standard treatment. Materials and Methods This is a retrospective study conducted in a single tertiary cancer center in south India. Forty patients with GBM who had their entire treatment done at this center were identified, and their primary tumor tissue blocks were retrieved. Genomic DNA was extracted, and molecular analysis was performed and analyzed. The results of mutational analysis were correlated with treatment outcome of the patients. Statistical Analysis Survival outcome was analyzed using the Kaplan–Meier method. The log-rank test was used to assess the association between the groups and various parameters. Results Our study showed a similar incidence of EGFR vIII alterations as published in world literature, but we did not find any difference in overall survival (OS) and progression-free survival (PFS) in patients with EGFR vIII mutation compared with nonmutant cohort. Conclusions Contrary to the existing literature which indicated EGFR vIII alterations to be a negative prognostic indicator, our study did not find it to be an independent predictor of prognosis among Indian GBM patients treated with present standard of care.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: Results from two phase 1 clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1038-1038
Author(s):  
Sara A. Hurvitz ◽  
Haeseong Park ◽  
Sophia Frentzas ◽  
Catherine M. Shannon ◽  
Katharine Cuff ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Salivary Gland Cancer ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Two Phase ◽  
Site Specific ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
A Site

1038 Background: ARX788 is a site-specific, homogeneous, and highly stable ADC. The payload AS269 is conjugated to the synthetic amino acids para-acetylphenylalanine (pAF) in a humanized anti-HER2 mAb. ARX788 demonstrated promising activity in HER2-positive, HER2-low, and T-DM1 resistant tumors in preclinical studies. Here we present the phase 1 clinical data evaluating the safety, antitumor activity, and PK of ARX788 in advanced solid tumors. Methods: The standard 3+3 design (0.33 - 1.5 mg/kg; Q3W or Q4W) is used to determine the MTD and/or RP2D in two phase 1 studies in HER2-positive solid tumors in U.S. and Australia (ACE-Pan tumor-01) and in HER2-positive breast cancers in China (ACE-Breast-01). The efficacy endpoints include ORR and DCR. Intensive PK sampling in first 3 cycles is performed to characterize serum PK profiles of ARX788, total Ab, and pAF-AS269. Results: 69 and 34 heavily pretreated patients received ARX788 monotherapy in the ACE-Breast-01 (median 6 prior lines of therapy) and ACE-Pan tumor-01 trial (including breast, gastric/GEJ, NSCLC, ovarian, urothelial, biliary track, endometrial, and salivary gland cancer) respectively. Dose escalation for both studies have been completed with no DLT reported. MTD has not been reached. ARX788 was generally well tolerated with most AEs being grade 1 or 2. The most common grade >3 AEs include ocular AEs (5.7 %) and pneumonitis (4.3%) in the ACE-Breast-01 trial; pneumonitis (2.9%) and fatigue (2.9%) in the ACE-Pan tumor-01 trial. Low systemic toxicities in terms of the incidence rate and grade (as shown in table). No treatment-related death. In the 1.5 mg/kg cohort, ORR was 74% (14/19) and 67% (2/3) for ACE-Breast-01 and ACE-Pan tumor-01, respectively. DCR was 100%. Median DOR or median PFS has not been reached. PK profiles for total antibody and ARX788 were generally comparable across all dose levels. Mean T1/2 for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg. Serum pAF-AS269 concentrations peaked with a median time of 168 h. Serum exposure of pAF-AS269 was low with the Cmax and AUC at cycle 1 being approximately 0.1% and 0.18% of those for ARX788 on a molar basis, respectively. Conclusions: High stability of ARX788 and low serum exposure of pAF-AS269 may underlie the low systemic toxicity, which differentiates it from other ADCs. Clinical trial information: NCT032550070 .[Table: see text]

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