Another patient with a PR and 2 of three sufferers with SD also formulated therapy limiting hematologic toxicity. None in the individuals with PD suffered therapy limiting hematologic toxicity. Combining imatinib with hydroxyurea is helpful in a subset of sufferers with malignant glioma. On the other hand, myelosuppression can persist for weeks to months following discontinuing the regimen, precluding even more chemotherapy. Our data also suggest a doable connection in between hema tologic toxicity and condition management, implying that glioma and marrow stem cells could possibly share a widespread sensitivity to this chemotherapy routine. If addi tional sufferers expertise treatment limiting myelosuppression inside the setting of response or prolonged sickness stabilization, consideration ought to be provided to the collection of peripheral stem cells prior to remedy.
Autologous stem cell rescue continues to be made use of to sustain remedy with imatinib for leukemia sufferers with marrow aplasia and may well also make it possible for continuation of imatinib and hydroxyurea treatment for responding glioma individuals. TA 53. A PHASE I TRIAL OF Mixture MOTEXAFIN GADOLINIUM AND TEMOZOLOMIDE IN MALIGNANT GLIOMAS W. R. Shapiro,one L. S. Ashby,one S. selelck kinase inhibitor Phan2, 1Barrow Neurological Institute, Phoenix, AZ, selleck chemical USA, 2Pharmacyclics, Sunnyvale, CA, USA MGd is actually a novel antineoplastic agent that targets tumors, inhibits thio redoxin reductase, and generates reactive oxygen species by redox cycling. Preclinical models demonstrate that MGd enhances the cytotoxic activ ity of quite a few chemotherapy medication which include temozolomide. This phase I trial evaluated the security and tolerability of MGd in combination with temozolomide in sufferers with recurrent malignant gliomas. Individuals with malignant gliomas and sufficient bone marrow, hepatic, and renal function had been eligible.
Cohorts of 3 to 6 individuals had been taken care of with escalating doses of MGd, commencing at 2. 5 mg/kg i. v. followed by temozolomide at 150 mg/m2 or 200 mg/m2. 60 minutes later. Deal with ments had been repeated q4 weeks. Twenty sufferers have been handled with MGd in 4 cohorts and temozolomide. Eleven sufferers had been males and 9 had been gals. Diagnoses integrated 9 individuals with glioblastoma multiforme, 3 with anaplastic astrocytoma, 7 with anaplastic oligodendroglioma, and one particular with one other diagnosis. Eleven patients had acquired prior systemic therapy which include 6 who previously obtained temozolomide. All sufferers had previously obtained radiation therapy. No dose limiting toxici ties occurred. The MGd associated toxicities that have been reported in. 10% of individuals include digital skin discoloration and blisters, nausea, diarrhea, vomiting, fatigue, and pruritis. Adverse occasions grade III have been arthralgia, extremity pain, and nail bed tenderness in one patient every. Two individuals discontinued remedy for drug linked adverse events.