A phase II study of sunitinib administered in a continuous daily regimen in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4529-4529 ◽  
Author(s):  
P. H. De Mulder ◽  
J. Roigas ◽  
S. Gillessen ◽  
S. Srinivas ◽  
P. Pisa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Colon Perforation ◽  
Efficacy Data ◽  
Significant Difference ◽  
Hand Foot Syndrome

4529 Background: Renal cell carcinomas are known for their vascularity and production of high levels of VEGF. Sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor of multiple receptors including VEGFR, PDGFR, KIT, RET, and FLT3, has previously demonstrated significant efficacy in 168 patients (pts) with mRCC, with a 42% objective response rate (ORR) at 50 mg/day in 6-week (wk) cycles of 4 wks on treatment followed by 2 wks off. This study sought to determine the efficacy and safety of single-agent sunitinib in mRCC when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints includedprogression-free survival, adverse events (AEs) and quality of life measures. Results: A total of 88/100 planned pts have been randomized to date: AM (43) and PM (45), and enrollment will be completed by end January 2006. 44 pts have been on continuous sunitinib treatment at 37.5 mg/day for >16 wks (3), >12 wks (9), >8 wks (12), and >4 wks (20). 2 pts (2.3%) discontinued (colon perforation and renal insufficiency) and 9 (10.2%) dose reduced to 25 mg/day due to grade 2/3 AEs: mucositis (2), hand-foot syndrome (2), thrombocytopenia (2), asthenia (1), nausea/diarrhea (1), and neutropenia (1). Preliminary efficacy data show some tumor shrinkage in the majority of patients evaluated at 4 wks, with 3 initial partial responses. There has been no significant difference between pts who received AM or PM doses. The most commonly reported AEs were mucositis, fatigue, hair/skin discoloration, and hand-foot syndrome. Conclusions: Sunitinib administered at a continuous dose of 37.5 mg/day was generally well tolerated; only a few patients required treatment breaks and/or dose reduction. Preliminary efficacy data are encouraging. Mature data will be presented. [Table: see text]

Randomized phase II study of docetaxel plus vandetanib (D+V) versus docetaxel followed by vandetanib (D-V) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (OC): SWOG S0904.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5015-5015 ◽  
Author(s):  
Robert L. Coleman ◽  
James Moon ◽  
Anil Sood ◽  
Donna Branham ◽  
James Edwin Delmore ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Primary Therapy ◽  
Antitumor Effects ◽  
Angiogenic Therapy ◽  
Randomized Phase Ii ◽  
Therapy Stratification

5015 Background: Antiangiogenesis therapy has led to antitumor effects both preclinically and clinically. Vandetanib (V) is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET. These targets are of interest in OC care, as targeting has shown anti-tumor efficacy, particularly in combination with taxanes. We explored the efficacy, safety, and toxicity of docetaxel (D) and V in women with recurrent OC. Methods: Women with resistant, refractory, or progressive/persistent OC were eligible for this randomized phase II study provided they had not received D or V for recurrent disease. Patients were allowed to receive other anti-VEGF targeted agents for primary therapy (stratification variable). Up to 3 additional cytotoxic regimens for recurrence were allowed. Patients were allocated 1:1 to D(75 mg/m2, I.V.)+V (100 mg daily, p.o.) or D(75 mg/m2). Patients receiving single agent D were allowed to crossover to V upon progression (D-V). The primary endpoint was PFS. Other objectives were: OS, objective response (ORR), and frequency/severity of adverse events. The study was designed with 84% power to detect a 1.55 PFS hazard ratio using a one-sided P of 0.1. Results: 131 patients were enrolled; 5 were excluded (1 ineligible, 4 eligible but untreated). 9% had received prior anti-angiogenic therapy. 61 patients on D+V were assessable for toxicity; 19 (31%) had treatment-related G4 events, primarily hematologic. Similarly, 17 (26%) of 65 patients receiving D alone had G4 events, primarily hematologic. 34 (52%) patients crossed over to V; no G4 events were recorded among 32 evaluable patients. G3 diarrhea was observed in 14% of D+V patients; 5% D-V patients. G3 acneiform rash occurred in 2% and 0%, respectively. The median PFS estimates were 3.0 mos (D+V) vs 3.5 (D-V); HR (PFS): 0.98 (80% CI:0.75-1.27). For OS, the median estimates were 14 mos (D+V) vs 12 mos (D-V); HR (OS):0.84 (80% CI:0.56-1.28). ORR was 14% and 17%, respectively. Crossover V response was 4% (1/27 measurable patients). Conclusions: D+V was well tolerated in this population however, did not prolong PFS with respect to D.

A phase II study of infigratinib in previously treated advanced/metastatic cholangiocarcinoma with FGFR gene fusions/alterations.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS356-TPS356
Author(s):  
Milind M. Javle ◽  
Robin Kate Kelley ◽  
Christoph Springfeld ◽  
Ghassan K. Abou-Alfa ◽  
Teresa Macarulla ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Objective Response ◽  
Genetic Alterations ◽  
Gene Fusions ◽  
Fgfr2 Gene

TPS356 Background: The FGFR family plays an important role in cholangiocarcinoma, with FGFR2 gene fusions detected in about 15% of patients with cholangiocarcinoma. Infigratinib is an FGFR1–3-selective oral tyrosine kinase inhibitor under evaluation in multiple indications including front-line and pre-treated cholangiocarcinoma. CBGJ398X2204 is an ongoing phase II study evaluating the efficacy of single-agent infigratinib in patients with advanced or metastatic cholangiocarcinoma with FGFR genetic alterations who have received prior gemcitabine. Methods: Study CBGJ398X2204 consists of 3 cohorts and patients in all cohorts receive oral infigratinib once daily for 21 days of a 28-day treatment cycle. Treatment will continue until progressive disease, intolerance, withdrawal of consent, or death. Cohort 1 includes patients with FGFR2 gene fusions or translocations. Cohort 2 includes patients with FGFR genetic alterations other than FGFR2 gene fusions (patients in both Cohorts 1 and 2 must not have received any prior FGFR inhibitors). Cohort 3 includes patients with FGFR2 gene fusions who have received prior treatment with a selective FGFR inhibitor other than infigratinib. The primary endpoint is objective response rate (ORR, RECIST v1.1 per central review). Secondary endpoints include overall survival and overall response rate (per investigator). Safety, pharmacokinetics, and exploratory genetic alterations/biomarkers will also be measured. The study was initiated in 2014 and has a planned enrollment of up to 160 patients across all 3 cohorts (120 in Cohort 1, 20 in Cohort 2, and 20 in Cohort 3). Cohort 1 has completed enrollment and findings from this Cohort are the focus of a separate abstract submitted to the meeting. Results are not currently available from Cohorts 2 and 3 (trial in progress). Clinical trial information: NCT02150967.

Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4603-4603 ◽  
Author(s):  
Y. Bang ◽  
Y. Kang ◽  
W. Kang ◽  
N. Boku ◽  
H. Chung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Mucosal Inflammation ◽  
Open Label ◽  
Preliminary Results ◽  
Grade 3

4603 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. We investigated the safety and activity of SU monotherapy in pts with previously-treated gastric cancer. Preliminary results from this open-label, multicenter, phase II study are reported. Methods: Eligibility criteria included measurable stage IV disease; 1 prior chemotherapy regimen; and ECOG PS =1. Pts took SU 50 mg/day for 4 wks followed by 2 wks off treatment in 6-wk cycles. A Simon 2-stage design was used with a target accrual of 38 pts in the first stage, expanding to 63 pts if =2 partial responses (PRs) were observed. The primary endpoint was RECIST-defined objective response rate. Secondary endpoints included duration of response and safety. Pharmacokinetic (PK) Ctrough parameters were also monitored. Results: As of Sept 15 2006, 38 evaluable pts (median age 56 years [range 29–78]; 2–3 metastatic sites [63%]; prior treatment with 5-FU ± platinum [P] [24%], capecitabine ± P [13%], TS-1 ± P [26%], other [37%]) have received a median of 2 SU cycles (range 1–3). Of 21 pts evaluable for efficacy, 1 PR has been confirmed and 8 pts had stable disease (SD), 4 with SD for =2 cycles. The most commonly reported AEs were typically grade 1/2 in severity and included stomatitis, skin discoloration, fatigue, anorexia, diarrhea, hand-foot syndrome (HFS), nausea and vomiting. Grade 3/4 toxicities included HFS (10.5%), fatigue (7.9%), anorexia (7.9%) and mucosal inflammation (5.3%). Grade 3/4 hematologic toxicities included neutropenia (29%), thrombocytopenia (29%) and anemia (11%). 7 pts experienced serious SU- related AEs requiring dose modifications in 3 pts and treatment discontinuation in 1 pt. Preliminary PK investigations indicate that concentrations seen in gastric pts are similar to those seen in other pts treated with SU. Conclusions: These initial findings show that SU is generally well tolerated and may have single-agent antitumor activity in pre-treated gastric cancer pts. Further trials with SU in combination with standard chemotherapy regimens are planned. No significant financial relationships to disclose.

A phase II study of oral ENMD-2076 administered to patients (pts) with advanced soft tissue sarcoma (STS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS10593-TPS10593
Author(s):  
Herbert H. F. Loong ◽  
Martin E. Blackstein ◽  
Abha A. Gupta ◽  
David Hogg ◽  
Helen Mackay ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Dose Escalation Study ◽  
Significance Level

TPS10593 Background: The use of angiogenic and Aurora kinase inhibitors has been shown to abrogate tumour growth in STS. ENMD-2076 is an oral Aurora A and angiogenic kinase inhibitor that has demonstrated single-agent activity in sarcoma cell lines. Prior phase I dose escalation study has determined the maximum tolerated dose of ENMD-2076 to be 160mg/m2, with a recommended starting dose of 275mg/day. In that study, one patient with STS experienced durable stable disease (21 months). Primary Objective: To determine the activity of ENMD-2076 in advanced STS (with ≤1 prior line of therapy) as defined by 6-month progression-free survival rate (PFSR). Secondary Objectives: (i) To determine the safety and tolerability of ENMD-2076, (ii) To determine the objective response rate (ORR) as per RECIST criteria and duration of response, (iii) To perform exploratory analysis of factors associated with survival. Study Design and Methodology: This is a single-center, open-labeled phase II study of ENMD-2076 in advanced STS. Pts are commenced on 275 mg daily dose on a 28 day cycle. Treatment-emergent adverse events will be assessed by the NCI-CTCAE (4.0). Radiographic or clinical tumour measurements will occur every 2 cycles. Sample Size Justification: It is assumed that ENMD-2076 shall be deemed non-efficacious in this population if the true 6- month PFSR probability is <15% (p0), whilst a 6-month PFSR probability >40% will be considered positive for activity. This translates to a minimum of 21 evaluable subjects required in the study, within which ≥6 patients need to have shown lack of progression at 6 months in order for this study to be considered positive. This design has a significance level of 10% and power of 90%. Methods: PFSR at 6-months will be estimated using the Kaplan-Meier method. ORR will be estimated and 2-sided 95% exact binomial confidence interval will be provided. Study Progress: At deadline for abstract submission, 3 patients have been enrolled onto this study. Clinical trial information: NCT01719744.

A phase II study of sitravatinib (Sitra) in combination with nivolumab (Nivo) in patients (Pts) undergoing nephrectomy for locally-advanced clear cell renal cell carcinoma (accRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 312-312
Author(s):  
Jose A. Karam ◽  
Pavlos Msaouel ◽  
Surena F. Matin ◽  
Matthew T Campbell ◽  
Amado J. Zurita ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Cell ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Unmet Need ◽  
Cell Renal Cell Carcinoma

312 Background: Sitra is a spectrum-selective receptor tyrosine kinase inhibitor (TKI) that targets TAM receptors (TYRO3, AXL, MERTK), VEGFR2, c-Kit, and MET. These receptors regulate several immune suppressive cell types in the tumor microenvironment, including M2-polarized macrophages, MDSCs, and T regulatory cells, which are implicated in resistance to checkpoint inhibitors. ccRCC is characterized by upregulation of VEGF and overexpression of MET and AXL. Sitra may combine effectively with immune checkpoint inhibition to augment antitumor activity in ccRCC. About 39% of patients with accRCC who receive surgery with curative intent relapse representing an unmet need in this setting. Together these data support the evaluation of neoadjuvant sitra with nivo in accRCC. Methods: This phase II study (NCT03680521) evaluated sitra and nivo in pts with locally- advanced ccRCC who were candidates for curative nephrectomy. Single-agent sitra (120 mg) was administered daily (QD) for 2 weeks, with nivo (240 mg intravenously Q2W) added to sitra for 4-6 weeks. A plan for potential dose de-escalation was implemented using a modified toxicity probability interval method with a maximum toxicity of 20% at the tolerated dose. Pts underwent pathology/tissue evaluation at 3 timepoints: biopsy prior to treatment, biopsy prior to the addition of nivo, and nephrectomy specimen evaluation at time of nephrectomy. The primary endpoint was objective response (RECIST 1.1); secondary endpoints included safety, PK, and correlative immune effects (selected protein and gene expression and immune cell populations). Results: A total of 20 pts were evaluated for safety (95% had T3 or higher stage tumors, 65% with baseline hypertension). Dose-limiting toxicities (DLTs) led to a dose de-escalation, resulting in 7 pts treated at 120 mg QD sitra and 13 pts treated at 80 mg QD. DLTs included grade 3 (Gr3) hypertension (n=6); deep vein thrombosis and pulmonary embolism (Gr3) were observed in 1 additional pt. Median duration of sitra treatment was 6.3 weeks at the 80 mg dose and 7.1 weeks at the 120 mg dose. With a median follow-up of 9.4 months after initiation of systemic therapy, no pts have relapsed. In 17 pts evaluable for efficacy, the investigator-assessed confirmed ORR was 11.8%, including 2 PRs (33.3% ORR in pts who received 120 mg sitra). No pts experienced progressive disease while on therapy. Median DFS was not reached. There was 1 delayed surgery due to nivo-related thyroiditis that resolved. Reported TRAEs: Gr1/Gr2 in 55% of pts (dysphonia 50%, fatigue 45%, diarrhea 40%, hypertension 30%, increased ALT 30%), Gr3 in 45% of pts (hypertension 30%). There were no Gr4/Gr5 TRAEs. Correlative blood and tissue analyses will be presented. Conclusions: The combination of sitra and nivo is clinically active with a manageable safety profile as a neoadjuvant therapy for accRCC. Clinical trial information: NCT03680521 .

scholarly journals Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma

2021 ◽  
Author(s):  
Cara Kenney ◽  
Tricia Kunst ◽  
Santhana Webb ◽  
Devisser Christina ◽  
Christy Arrowood ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Phase Ii ◽  
Pancreas Cancer ◽  
Phase Ii Study ◽  
Mapk Pathway ◽  
Single Agent ◽  
Objective Response ◽  
Ductal Adenocarcinoma ◽  
Active Inhibitor ◽  
Orally Active

SummaryBackground Preclinical evidence has suggested that a subset of pancreatic cancers with the G12R mutational isoform of the KRAS oncogene is more sensitive to MAPK pathway blockade than pancreatic tumors with other KRAS isoforms. We conducted a biomarker-driven trial of selumetinib (KOSELUGO™; ARRY-142886), an orally active, allosteric mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, in pancreas cancer patients with somatic KRASG12R mutations. Methods In this two-stage, phase II study (NCT03040986) patients with advanced pancreas cancer harboring somatic KRASG12R variants who had received at least one standard-of-care systemic therapy regimen received 75 mg selumetinib orally twice a day until disease progression or unacceptable toxicity occurred. The primary outcome of the study was best objective response (BOR). Results From August 2017 to February 2018 a total of 8 patients with confirmed somatic KRASG12R mutations and a median age of 61.5 years were treated with selumetinib. Seven out of eight (87.5%) had received two or more lines of prior systemic chemotherapy. After a median follow-up period of 8.5 months (range 2 to 20), three patients had stable disease for more than 6 months while receiving selumetinib. No patients achieved an objective partial response. Median progression-free survival (PFS) was 3.0 months (95% CI, 0.8–8.2) and median overall survival (OS) 9 months (95% CI, 2.5–20.9). Conclusion This study in heavily pre-treated pancreatic adenocarcinoma patients suggests alternative strategies beyond single agent MEK inhibition are required for this unique, molecular subset of pancreatic cancer patients. The trial was registered on February 2nd, 2017 under identifier NCT03040986 with ClinicalTrials.gov.

Multi-institutional phase II study of carboplatin-gemcitabine combination chemotherapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18179-18179
Author(s):  
J. Sasaki ◽  
H. Uramoto ◽  
K. Kashiwabara ◽  
H. Kishi ◽  
E. Moriyam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Group Performance ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Grade 3

18179 Background: Because elderly pts may tolerate platinum-based combination chemotherapy poorly, single-agent chemotherapy is selected for the treatment regimen. However, retrospective subgroup analyses have consistently indicated that elderly pts indeed benefit from platinum-based combination chemotherapy as well as their younger counterparts. This phase II study evaluated the efficacy and safety of carboplatin-gemcitabine combination chemotherapy in elderly pts with advanced NSCLC. Methods: Fifty-four pts aged more than 70 years old (median, 77; range, 70–88) with previously untreated advanced NSCLC were enrolled on this trial. Additional criteria included the presence of measurable lesions, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Pts received carboplatin at an area under the curve of 4 mg/ml/min on the first day and gemcitabine at 1000 mg/m2 on the first and eighth day of consecutive 3 week periods. The primary endpoint was to determine the objective response rate of this platinum-doublet regimen. The RECIST criteria were used to measure response. Results: Enrolled pts included 15/39 with stage IIIB/IV diseases. Fifty-one out of enrolled pts were eligible for efficacy and safety analyses. The median number of treatment cycles was 4 (range, 1–7). Fifteen partial responses (response rate: 29%) were obtained. The median TTP was 118 days. Hematological toxicities of grade 3/4 included leukopenia (46%), neutropenia (72%) and thrombocytopenia (50%). Non-hematological toxicities of grade 3/4 included nausea (6%), appetite loss (7%), fatigue (7%) and infection (9%). Conclusions: The combination carboplatin-gemcitabine at these doses has shown activity with a favorable toxicity profile for fit elderly pts with advanced NSCLC. No significant financial relationships to disclose.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Decreased toxicity schedule of suitinib in renal cell cancer: 2 weeks on/1 week off

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16113-e16113
Author(s):  
F. Gyergyay ◽  
K. Nagyványi ◽  
I. Bodrogi
Keyword(s):  
Weight Loss ◽  
Side Effects ◽  
Dose Reduction ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Objective Response ◽  
Dose Intensity ◽  
Hand Foot Syndrome

e16113 Background: Sunitinib (SU) is an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET approved for treatment of metastatic renal cell cancer (mRCC). Pharmacokinetics and pharmacodynamics suggest that dose reduction might decrease the plasma concentration of SU and its major metabolite to an ineffective level. Methods: Pts with mRCC, measurable disease, ECOG PS 0–2 received SU 50 mg po daily 4 weeks on/2 weeks off. Results: Of 36 pts, median age 59.5 yrs (range 42–83), M/F (26:10), ECOG: 0 (21); 1 (9); 2 (6); prior nephrectomy (35),prior radiation therapy (28), prior cytokine therapy: IFNα (25), IL-2+IFNα (9) none (2); pts with 1 metastatic organ (24); 2 metastatic sites (7); ≥ 3 sites (5); Sites of metastases: Lung (27), Bone (11), Liver (3); MSCC risk factors: 0 (20), 1–2 (14); ≥3 (2). Objective response occurred: PR (13) 42%; CR (2) 5%; SD (9) 25%. Number of cycles (6 weeks cycles) given was: 162 (2–15).Main side effects were: fatigue 42% (Gr≥3: 17%), diarrhoea 42% (Gr≥3: 25%), nausea 31% (Gr≥3: 6%), stomatitis 10%, anorexia 10%, weight-loss 20% (Gr≥3: 11%), hand-foot syndrome 39% (Gr≥3: 17%), hypertension 28%, anemia 25%, neutropenia 8%, thrombopenia 11%, hypothyroidism 11%. Five cases of dose reduction and two cases of treatment discontinuation occurred due to toxicity. During the second part of the study if serious toxicity had been reported, instead of dose reduction, two weeks on and one week off schedule (50mg daily) had been offered to pts. 14 pts (79 cycles) were treated according to the schedule. Short term side effects decreased significantly: fatigue 28%, diarrhea 14%, nausea 14%, stomatitis 7%, anorexia 7%, weight-loss 7%, hand-foot syndrome 14%, hypertension 7%, anemia 14%, hypothyroidism 11%. Conclusions: Further prospective studies are needed to confirm the better tolerance of the SU, without decreasing the dose intensity of the treatment. No significant financial relationships to disclose.

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