TY - JOUR
T1 - Multicenter Phase II trial assessing effectiveness of imatinib mesylate on relapsed or refractory KIT-positive or PDGFR-positive sarcoma
AU - Sugiura, Hideshi
AU - Fujiwara, Yasuhiro
AU - Ando, Masashi
AU - Kawai, Akira
AU - Ogose, Akira
AU - Ozaki, Toshifumi
AU - Yokoyama, Ryohei
AU - Hiruma, Toru
AU - Ishii, Takeshi
AU - Morioka, Hideo
AU - Mugishima, Hideo
N1 - Funding Information:
Acknowledgments. The authors express sincere appreciation to Tadashi Hasegawa, MD, Takashi Nikaido, MD, and Shinji Sakurai, MD for diagnoses based on histopathology. The authors thank Masahiro Saito, MD, Katsuji Shinagawa, MD, and Kensei Tobinai, MD for evaluation of safety analysis as well as Masahiko Kusumoto, MD and Masahiro Tsuboi, MD for evaluation of the effectiveness analysis. The authors thank also Masahiro Takeuchi, PhD and Shiro Takahashi, PhD for assistance with statistics. Imatinib was provided as an investigational drug by Novartis Pharmaceutical Co., Ltd., Tokyo, Japan. This study was supported by the promotion program for registration-directed clinical trials by the Japanese Medical Association (CCT1501).
PY - 2010/9
Y1 - 2010/9
N2 - Background: Imatinib myselate is a molecularly targeted drug that inhibits Abl tyrosine kinase, as well as type III tyrosine kinase receptors such as platelet-derived growth factor receptor (PDGFR), KIT, colony-stimulating factor 1 receptor (CSF-1R), and discoidin domain receptor (DDR). Ph1 chromosome-positive chronic myeloid leukemias (CMLs), KIT-positive gastrointestinal stromal tumors (GISTs), and PDGFR-positive dermatofibrosarcoma protuberans (DFSP) have been reported to be responsive to imatinib treatment. We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Methods: Patient ages ranged from 12 and 75 years. Eligibility criteria included (1) metastatic sarcomas with a definitive diagnosis based on histopathology or that were completely unresectable and locally advanced; (2) relapsed or refractory cases that had completed standard treatment; and (3) a tumor confirmed by immunohistochemical staining to be KIT- or PDGFR-positive. A 600-mg dose of imatinib was administered to patients once a day, with each patient receiving six courses of the drug and each course lasting 4 weeks. In cases categorized as stable or progressive, the imatinib dose was increased to 800 mg/day administered twice daily. Results: A total of 25 patients who met the eligibility criteria were enrolled in the trial; 22 were evaluated for response. The response rate with a 600 mg/day dose of imatinib was 4.5% (0 complete response, 1 partial response). There were no other objective responses after increasing imatinib to 800 mg/day (0/10). We estimated 50% progression-free survival to be 61.0 days for an imatinib dose of 600 mg/day based on the Kaplan-Meier method. Side effects of imatinib were generally similar to those observed in previous clinical trials. Conclusions: Our results did not indicate effectiveness of imatinib monotherapy at a dose of 600 or 800 mg/day in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Our findings suggest the need to evaluate the synergistic effect of combination therapy with other anticancer drugs.
AB - Background: Imatinib myselate is a molecularly targeted drug that inhibits Abl tyrosine kinase, as well as type III tyrosine kinase receptors such as platelet-derived growth factor receptor (PDGFR), KIT, colony-stimulating factor 1 receptor (CSF-1R), and discoidin domain receptor (DDR). Ph1 chromosome-positive chronic myeloid leukemias (CMLs), KIT-positive gastrointestinal stromal tumors (GISTs), and PDGFR-positive dermatofibrosarcoma protuberans (DFSP) have been reported to be responsive to imatinib treatment. We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Methods: Patient ages ranged from 12 and 75 years. Eligibility criteria included (1) metastatic sarcomas with a definitive diagnosis based on histopathology or that were completely unresectable and locally advanced; (2) relapsed or refractory cases that had completed standard treatment; and (3) a tumor confirmed by immunohistochemical staining to be KIT- or PDGFR-positive. A 600-mg dose of imatinib was administered to patients once a day, with each patient receiving six courses of the drug and each course lasting 4 weeks. In cases categorized as stable or progressive, the imatinib dose was increased to 800 mg/day administered twice daily. Results: A total of 25 patients who met the eligibility criteria were enrolled in the trial; 22 were evaluated for response. The response rate with a 600 mg/day dose of imatinib was 4.5% (0 complete response, 1 partial response). There were no other objective responses after increasing imatinib to 800 mg/day (0/10). We estimated 50% progression-free survival to be 61.0 days for an imatinib dose of 600 mg/day based on the Kaplan-Meier method. Side effects of imatinib were generally similar to those observed in previous clinical trials. Conclusions: Our results did not indicate effectiveness of imatinib monotherapy at a dose of 600 or 800 mg/day in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Our findings suggest the need to evaluate the synergistic effect of combination therapy with other anticancer drugs.
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U2 - 10.1007/s00776-010-1506-9
DO - 10.1007/s00776-010-1506-9
M3 - Article
C2 - 20953927
AN - SCOPUS:78149452583
SN - 0949-2658
VL - 15
SP - 654
EP - 660
JO - Journal of Orthopaedic Science
JF - Journal of Orthopaedic Science
IS - 5
ER -