Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Aug 2001
Multicenter Study Clinical TrialAnalysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG).
All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. ⋯ Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.
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Cancer Chemother. Pharmacol. · Aug 2001
Multicenter Study Clinical TrialClinical trials of a mouse-human chimeric anti-CD20 monoclonal antibody (rituximab) for B cell non-Hodgkin's lymphoma in Japan.
Rituximab, a mouse-human chimeric anti-CD20 monoclonal antibody, induces apoptosis in B cell non-Hodgkin's lymphoma (B-NHL) cells, in addition to lysis by complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. A group of 12 patients with relapsed CD20+ B-NHL were enrolled in a phase I study; 4 received rituximab 250 mg/m2 and 8 375 mg/m2 once weekly for 4 weeks. Grade 1 or 2 infusion-related toxicity such as 'flu-like symptoms and skin reactions were observed. ⋯ The PFS times of patients with higher serum rituximab concentrations at day 14 (> or =70 microg/ml) and at 3 months (> or =10 microg/ml) were significantly longer than those of patients with lower concentrations (P=0.006 and P=0.0001, respectively). In conclusion, rituximab is more effective in indolent B-NHL than in MCL. Several prognostic factors and serum rituximab concentrations are useful for predicting the therapeutic efficacy.
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Cancer Chemother. Pharmacol. · Aug 2001
ReviewRadioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma.
Clinical trials of an yttrium-90 (90Y)-conjugated monoclonal antibody to CD20 in patients with relapsed B cell non-Hodgkin lymphoma (NHL) are reviewed. Ibritumomab is the murine parent anti-CD20 antibody engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA linker chelator attached to ibritumomab to form ibritumomab tiuxetan (Zevalin). ⋯ These results provide further evidence of the added value of 90Y. Therefore 90Y-ibritumomab tiuxetan radioimmunotherapy is a useful new treatment modality for patients with B cell NHL. Future trials are needed to define the optimal time in the disease course when this modality should be used.
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Cancer Chemother. Pharmacol. · Aug 2001
ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy.
The deregulated tyrosine kinase activity of the Bcr-Abl fusion protein has been established as the causative molecular event in chronic myelogenous leukemia (CML). Thus the Bcr-Abl tyrosine kinase is an ideal target for pharmacologic inhibition. ST1571 (formerly CGP57148B), is an Abl-specific tyrosine kinase inhibitor that in preclinical studies selectively kills Bcr-Abl-containing cells in vitro and in vivo. The results of clinical studies have demonstrated the potential of molecularly targeted therapies, and ST1571 is emerging as a new therapeutic agent for CML.