Entry Detail
| General information | |
| Database: | DB00580 |
| Objective: | The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). |
| Authors: | Vertheyij J, et al |
| Title: | Imatinib mesylate (STI571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other softtissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Groupphase II study. |
| Journal: | Eur J Cancer. |
| Year: | 2003 |
| PMID: | 12957454 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS) |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Results from an EORTC Soft Tissue and Bone Sarcoma Groupphase II study |
| Key Patients Feature: | Eligibility criteria included histologicallyprovenadvanced and/or metastatic GIST characterised by KITexpression, or any other subtype of STS, not necessarilyselected by KIT expression, graded according to theTrojani system and incurable by surgery or radiotherapy, excluding malignant mesothelioma, chondrosarcoma, neuroblastoma, osteosarcoma, Ewing¡¯ssarcoma and embryonal rhabdomyosarcoma.atients had to have at least one measurable targetlesion witha minimum size of at least one diameter52 cm, or 51 cm if measured on spiral computedtomography (CT) scan, with evidence of progressionwithin 6 weeks prior to study entry: No more thanone line of previous combination chemotherapy ortwo singleagent regimens were allowed. The chemotherapy should have been discontinued for more than4 weeks; for GIST, patients who had not been previously treated were also eligible: Patients had tohave had no previous radiation therapy to the soleindex lesion used to assess response and be aged greaterthan 15 years with a World Health Organization(WHO) performance status <2; an absolute neutrophilcount more than 1.5 109/l; platelet count morethan 100 109/l; serum creatinine 4120 micromol/lor calculated creatinine clearance (Cockcroftmethod) >1.1 ml/s; total bilirubin 430 micromol/l;no comedication withwarfarin was allowed. |
| Biomarker: | Immunohistochemical expression of KIT expression |
| Biomark Analysis: | This dose is active in patients with KITpositive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit. |
| Control Group Info: | single arm |
| Treatment Info: | were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). All tumours were subject to a stringent pathological review by an expert panel. Immunohistochemical expression of KIT expression was evaluated. |
| Primary End Point: | safety and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 51 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In GIST patients, the current response rates (RRs) are 4% complete remission (CR), 67% partial remission(PR), 18% stable disease (SD) and 11% progression (PD). 73% of GIST patients are free from progression at 1 year. In the otherSTS group, there were no objective responses |
| Disease Control Rate: | 0.9 |
| Median Time to Progression: | The median time to progression in this group of patients was 58 days |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent sideeffects were anaemia (92%), periorbital oedema (84%), skin rash (69%), fatigue (76%), nausea (57%), granulocytopenia (47%) and diarrhoea (47%). Most of these sideeffects were mild to moderate and no patient was taken off study due to sideeffects. Skin rashand periorbital oedema frequently seem to be self limiting, despite continued treatment. |
| Conclusions: | Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KITpositive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit. |