title: Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group.
abstract: In a phase I study conducted by the EORTC Soft Tissue and Bone Sarcoma Group, 40 patients with advanced soft tissue sarcomas, most of whom had gastrointestinal stromal tumors (GISTs), received imatinib at doses of 400 mg q.d., 300 mg b.i.d., 400 mg b.i.d., or 500 mg b.i.d. Dose-limiting toxicities, including severe nausea, vomiting, edema and rash, were seen at the highest dose level; the maximum tolerated dose was therefore 400 mg b.i.d. Imatinib was active in the group of 35 patients with GISTs, producing partial responses in 19 (54%) patients and stable disease in 13 patients (37%). Responding patients have now been followed for a minimum of 10 months. The most common side effects seen in patients continuing on therapy have been periorbital edema (40%), peripheral edema (37.5%), fatigue (30%), skin rash (30%) and nausea/vomiting (25%). Severe late myelosuppression has also been seen occasionally. Eighteen (51%) GIST patients continue to have partial responses and 11 (31%) continue with stable disease. Thus, 82% of patients with GISTs are still obtaining clinically important benefits with continued imatinib therapy. Some patients showed accelerated progressive disease shortly after starting imatinib. On the other hand, following drug withdrawal, 2 patients had reductions in tumor burden and remain alive without drug therapy. In summary, imatinib is generally well tolerated and has significant activity during long-term treatment of patients with advanced GISTs.
authors.affiliation: Department of Oncology, Catholic University Hospital, Leuven, Belgium. allan.vanoosterom@uz.kuleuven.ac.be
authors.forename: Allan T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: Ian R
authors.initials: IR
authors.lastname: Judson
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.forename: Herlinde
authors.initials: H
authors.lastname: Dumez
authors.forename: Eugenio
authors.initials: E
authors.lastname: Donato di Paola
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Martine
authors.initials: M
authors.lastname: Van Glabbeke
authors.forename: Sasa
authors.initials: S
authors.lastname: Dimitrijevic
authors.forename: Ole S
authors.initials: OS
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009372:Neoplasms, Connective Tissue / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012509:Sarcoma / Q000188:drug therapy*; D017154:Stromal Cells; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate