Compassionate Use Experience with Dasatinib Therapy in Patients after Imatinib and/or Nilotinib Failure.

Background: Dasatinib is a potent orally active, multi-targeted tyrosine kinase inhibitor that blocks signal transduction pathways implicated in the proliferation and survival of tumor cells. A European compassionate use trial was conducted to provide dasatinib to patients (pts) who were ineligible to be enrolled into the START-trials.

Methods: From April 2006 to February 2007, 26 pts were included in Germany. Diagnosis at inclusion: 9 Ph⁺ALL, 6 CML in accelerated phase, 5 CML in myeloid blast crisis, 2 biphenotypic Ph⁺ALL and 1 chronic phase CML. Additionally, 3 pts with systemic mastocytosis (SM), refractory to imatinib due to D816V mutation were also included. Pts had previously failed several chemotherapy regimens, including imatinib and/or nilotinib. Sixty-one percent were resistant, 35% were refractory and 4% intolerant to imatinib/nilotinib.

Results: Of 26 patients, there were 17 male and 9 female pts. The median age was 56 years (range, 22–80 years). The average daily dose of dasatinib was 137 mg with a median duration of therapy of 69.5d (range 3–252d). Six (23%) pts required transient treatment interruption, 2 (8%) due to non-haematological toxicity (dyspnea and increased hepatic values), 4 (15%) due to haematological toxicities. Twenty-one pts discontinued therapy for the following reasons: study related toxicity (23%), SCT (15%), death (8%), lost to follow-up (11%) and patient’s wish (4%). Two patients still remain on therapy. The response rate was CHR in 42%, complete (CCyR) cytogenetic response in 19%, and PCyR in 4% of the pts. For patients with diagnosed SM one partial HR, one stable disease and one progression have been recorded. Disease progression occurred in 19% of cases. Adverse events were transient and generally mild to moderate in severity. Generally, the observed AE profile was similar to that seen in previous research trials. For all pts, the most common hematological side-effects Grade 3/4 AEs reported were thrombocytopenia (23%), neutropenia (4%), and anemia (4%). Most frequent non-hematological side-effects included dyspnea in 23% of pts (no grade 3–4), edema in 23% (grade 3, 8%), diarrhea in 15% (grade 3, 4%), headache in 15% (no grade 3–4), bone and neck pain in 11% (grade 3, 8%) and pleural effusion in 8% (grade 3, 4%).

Conclusions: Dasatinib therapy appeared to be effective and was well tolerated in this difficult to treat patient population.