Sunitinib- and Sorafenib-lnduced Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor

2012 ◽  
Vol 46 (10) ◽  
pp. 1438-1438 ◽  
Author(s):  
Nedim Turan ◽  
Mustafa Benekli ◽  
Selcuk Cemil Ozturk ◽  
Salih Inal ◽  
Leyla Memis ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gastrointestinal Stromal Tumor ◽  
Renal Biopsy ◽  
Growth Factor Receptor ◽  
Stromal Tumor ◽  
Class Effect ◽  
Receptor Inhibition ◽  
Antiangiogenic Drugs ◽  
Grade 3 ◽  
Endothelial Growth Factor

Objective TO report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. Case Summary A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. Discussion Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. Conclusions The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.

scholarly journals Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib

2012 ◽  
Vol 5 (3) ◽  
pp. 651-656 ◽  
Author(s):  
Maria Caterina Pallotti ◽  
Maria Abbondanza Pantaleo ◽  
Margherita Nannini ◽  
Francesca Centofanti ◽  
Benedetta Fabbrizio ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gastrointestinal Stromal Tumor ◽  
Stromal Tumor ◽  
Time Treatment ◽  
Long Time

scholarly journals A Malignant Gastrointestinal Stromal Tumor of the Gallbladder Immunoreactive for PDGFRA and Negative for CD 117 Antigen (c-KIT)

HPB Surgery ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Athanasios Petrou ◽  
Pari Alexandrou ◽  
Alexandros Papalambros ◽  
Angelica Saetta ◽  
Paraskevi Fragkou ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Growth Factor Receptor ◽  
Stromal Tumor ◽  
Platelet Derived Growth Factor ◽  
Stromal Tumors ◽  
Cd 117 ◽  
Factor Receptor Alpha ◽  
Malignant Gists ◽  
First Time

Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT).

Incorporation of bevacizumab (B) and erlotinib (Er) with induction (Ind) and concurrent (Conc) carboplatin (Cb)/paclitaxel (P) and 74 Gy of thoracic radiotherapy in stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
M. A. Socinski ◽  
T. E. Stinchcombe ◽  
J. S. Halle ◽  
D. T. Moore ◽  
W. J. Petty ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Conformal Radiotherapy ◽  
Vascular Endothelial ◽  
Treatment Paradigm ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Endothelial Growth Factor ◽  
Pet Scans

7528 Background: Therapies directed at both the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways have been shown to improve survival in NSCLC and also have radiosensitizing properties. Methods: Pts receive Ind Cb (AUC 6), P (225 mg/m2) and B (15 mg/kg) on d1 and 22. PET scans are done pre- and post-I. On day 43, pts receive weekly Cb (AUC 2 x 7) and P (45 mg/m2 x 7) with 74 Gy (2 Gy/d) of thoracic conformal radiotherapy (TCRT). Cohort I (n=5) received B at 10 mg/kg q2wks during C therapy. Cohorts II and III (both n=5) received the same dose of B as in cohort I but also received Er at 100 mg and 150 mg po Tuesday - Friday of each week of C therapy, respectively. The primary endpoint is PFS at 1 year. All histologies are allowed including squamous (SQ) (an early stopping rule is in place for pulmonary hemorrhagic (PH) complications in SQ pts). Results: Thus far, 31 eligible PS 0–1 pts have been accrued (med age 62 yrs, range 41–74, 19 non- squamous, 12 SQ, 63% IIIA, 37% IIIB). Ind CbP + B has been well tolerated (1 gr 3 hypertension). No PH during Ind has been seen (including the 12 SQ cell pts). Response after Ind, 37% PR, 59% SD, 4% PD. Tumor volumes and PET SUVs have significantly decreased comparing pre- and post-Ind studies (p=0.0001 and p=0.0002, respectively). Cohort II has been expanded as the phase II regimen. To date, 25 of 26 (96%) pts have achieved the dose of 74 Gy (1 pt stopped at 60 Gy due to ILD). During Conc therapy, the principal toxicity has been esophagitis (53.8% gr 2, 19.2% gr 3). One grade 3 PH occurred in 1 SQ pt. One gr 5 late (> 2 mos after treatment) PH occurred in a SQ pt. Overall response rate following treatment - 68.2% (95% CI, 45–86%). The PFS at 1 year is 58% (95% CI, 34–76%) with an estmated 1-year overall survival rate of 79% (95% CI, 53–92%) which compares favorably to our historical experience. Conclusions: Preliminarily, we conclude that 1) Incorporation of B and E into this treatment paradigm appears feasible, 2) Esophagitis remains the primary toxicity, 3) Phase II accrual continues but early analysis of survival appears promising. Further details regarding the TCRT parameters and toxicity will be presented. [Table: see text]

Randomized phase II study of S-1/CDDP plus TSU-68 versus S-1/CDDP in patients with advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 72-72
Author(s):  
Kensei Yamaguchi ◽  
Wasaburo Koizumi ◽  
Hisashi Hosaka ◽  
Yasutaka Takinishi ◽  
Norisuke Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Parallel Group ◽  
Common Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

72^ Background: Gastric cancer (GC) is the second leading cause of cancer death in Japan as well as globally. Effective treatment of GC remains a therapeutic challenge. Although in the AVAGAST trial, bevacizumab was found to offer no survival benefit. Angiogenesis continues to be the standard treatment for GC, and thus, clinical trials on many anti-angiogenic drugs have been conducted. TSU-68 (orantinib) is an oral, angiokinase inhibitor targeting the vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. The present study evaluated the progression-free survival (PFS) and pharmacokinetics (PK) of TSU-68 in combination with Japanese standard S-1 and cisplatin (S-1/CDDP) in patients with advanced GC. Methods: In this open-label, multicenter, randomized, controlled, parallel-group, phase II trial, patients were randomized to Arm A (S-1/CDDP) or Arm B (TSU-68 plus S-1/CDDP). All patients received oral S-1 (40-60 mg/m2) twice daily for 21 days followed by a 14 day rest plus intravenous CDDP (60 mg/m2) on Day 8, repeated every 35 days. In Arm B pts received oral TSU-68 (400 mg/dose) alone, twice daily by addition 35 days. The primary endpoint was PFS. Results: In total, 93 patients were enrolled. For Arm A [male:female ratio], n=47 [35:11]; Arm B, n=45 [30:15]; the respective median age was 63.5 and 62.0 years. The median PFS was 7.0 and 6.8 months in Arms A and B, respectively (HR, 1.23; 95%CI, 0.74 to 2.05; P=0.425); the respective response rates were 56.5% and 62.2%. The most common grade 3/4 toxicities were neutropenia (Arms A and B, 34.8% and 31.1%) and hemoglobin (Arms A and B, 26.1% and 48.9%). There were no differences in other toxicities between the 2 arms, both treatments were tolerated, and no treatment-related deaths were observed. In the PK study, although Arm B had a significantly lower plasma exposure to FT, CDHP, and Oxo compared to Arm A, the exposure to 5-FU was not different between the 2 arms. The exposure to CDDP in Arm B was significantly but slightly lower than that in arm A. Conclusions: Thus,TSU-68 plus S-1/CDDP therapy did not prolong PFS of patients with advanced GC as compared with S-1/CDDP. Clinical trial information: JapicCTI-101327.

scholarly journals Gastrointestinal stromal tumor with nephrotic syndrome as a paraneoplastic syndrome: a case report

2014 ◽  
Vol 8 (1) ◽  
Author(s):  
Kiyoko Takane ◽  
Yutaka Midorikawa ◽  
Shintaro Yamazaki ◽  
Takahiro Kajiwara ◽  
Naoki Yoshida ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Case Report ◽  
Gastrointestinal Stromal Tumor ◽  
Paraneoplastic Syndrome ◽  
Stromal Tumor
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