a
One open-label, multicenter, phase 2 study was conducted testing Gleevec in diverse populations of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases.This study included 14patients with Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia (HES/CEL). HES patients were treated with 100mg to 1000mg of Gleevec daily. The ages of these patients ranged from 16 to 64years. A further 162patients with HES/CEL aged 11 to 78years were reported in 35published case reports and case series. These patients received Gleevec at doses of 75mg to 800mg daily. Hematologic response rates are summarized in Table 19. Response durations for literature patients ranged from 6+ weeks to 44 months.
Table 19 Response in HES/CEL Cytogenetic Abnormality Number of Patients Complete Hematological Response
N (%) Partial Hematological Response
N (%)
Positive FIP1L1-PDGFRα Fusion Kinase 61 61 (100%) 0%
Negative FIP1L1-PDGFRα Fusion Kinase 56 12 (21%) 9 (16%)
Unknown Cytogenetic Abnormality 59 34 (58%) 7 (12%)
Total 176 107 (61%) 23 (13%)
14.7 Dermatofibrosarcoma ProtuberansDermatofibrosarcoma Protuberans (DFSP) is a cutaneous soft tissue sarcoma. It is characterized by a translocation of chromosomes 17 and 22 that results in the fusion ofthe collagen type 1 alpha 1 gene and the PDGF B gene.
An open-label, multicenter, phase 2 study was conducted testing Gleevec in a diverse population of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases.This study included 12 patients with DFSP who were treated with Gleevec 800 mg daily (age range 23 to 75 years). DFSP was metastatic, locally recurrent following initial surgical resection and not considered amenable to further surgery at the time of study entry. A further 6 DFSP patients treated with Gleevec are reportedin 5 published case reports, their ages ranging from 18 months to 49 years. The total population treated for DFSP therefore comprises 18 patients, 8 of them with metastatic disease. The adult patients reported in the published literature were treated with either 400 mg (4 cases) or 800 mg (1 case) Gleevec daily. A single pediatric patient received 400 mg/m2/daily, subsequently increased to 520 mg/m2/daily. Ten patients had the PDGF B gene rearrangement, 5 had no available cytogenetics and 3 had complex cytogenetic abnormalities. Responses to treatment are described in Table 20.
Table 20 Response in DFSP Number of Patients (n=18) %
Complete Response 7 39
Partial Response * 8 44
Total Responders 15 83
* 5 patients made disease free by surgery
Twelve of these 18 patients either achieved a complete response (7 patients) or were made disease free by surgery after a partial response (5 patients, including one child) for a total complete response rate of 67%. A further 3 patients achieved a partial response, for an overall response rate of 83%. Of the 8 patients with metastatic disease, five responded (62%), three of them completely (37%). For the 10 study patients with the PDGF B gene rearrangementthere were 4 complete and 6 partial responses. The median duration of response in the phase 2 study was 6.2 months, with a maximum duration of 24.3 months, while in the published literature it ranged between 4 weeks and more than 20 months.
14.8 Gastrointestinal Stromal Tumors
Unresectable and/or Malignant Metastatic GIST
Two open-label, randomized, mul
