Home administration of s.c. bortezomib is cost-effective and is preferred by myeloma patients compared with hospital administration.

This prospective study aimed to assess the incidence of silent hypersensitivity to Escherichia coli asparaginase in the treatment of acute lymphoblastic leukemia (ALL). Thirty-three children with newly diagnosed ALL were included in the study and treated according to the FRALLE 2000 protocol. The 'A group' (n = 18) differed from the 'B-T group' (n = 15) by a less intensive chemotherapy, the absence of concurrent prednisone therapy, and different asparaginase administration modalities during the second intensification. Asparagine, asparaginase activity, and anti-asparaginase antibodies were measured in each phase before the next injection of asparaginase. Eighteen percent of children presented a silent hypersensitivity. Most of them were in the 'B-T group' (p = 0.07), and maintained low antibody titers throughout the treatment. Clinical hypersensitivity was statistically more frequent in group A (p = 0.002), and allergy occurred mainly during the second intensification when antibody concentrations were significantly increased. We did not find any significant difference between asparaginase activity or asparagine depletion between the silent hypersensitivity and clinical allergy groups. In all, the results of this study suggest that chemotherapy and corticosteroid therapy associated with asparaginase treatment can lower antibody production and contribute to maintaining a silent hypersensitivity state.

No abstract

This schedule with a high dose of ArgB proved to be highly toxic with liver insufficiency. We will be running another trial with lower doses of ArgB calculated from the schedule used in the experimental model, starting at a dose of 20 mg kg(-1) day(-1) for ArgB and 200000 UI kg(-1) day(-1) IL-2, every 8 h.

A significant antitumor effect was previously observed with radioimmunotherapy using anti-carcinoembryonic antigen 131 I-F6 monoclonal antibody in medullary thyroid cancer-bearing nude mice. Nevertheless, no complete response was observed. As seen with chemotherapy, drugs targeting the tumor microenvironment might improve radioimmunotherapy efficacy. This study evaluated the toxicity and efficacy of combining radioimmunotherapy with thalidomide or a cyclopeptidic vascular endothelial growth inhibitor (CBOP11) in mice grafted with the TT human medullary thyroid cancer cell line. Methods: Six to 10 nude mice treated with 92.5 MBq of 131 I-F6 in association with 200 mg/kg/d of oral thalidomide during 20 d by force-feeding or 0.45 mg/kg/d of CBOP11 during 25 d using subcutaneous minipumps were compared with control mice receiving either treatment or naked F6 or nonspecific 131 I-734. Combined therapies included 131 I-F6 at day 0 followed by thalidomide between days 20 and 40, thalidomide between days 0 and 20 followed by 131 I-F6 at day 25, 131 I-F6 at day 0 and CBOP11 between days 0 and 25, CBOP11 between days 0 and 25 followed by 131 I-F6 at day 25, and 131 I-F6 at day 0 followed by CBOP11 between days 20 and 45. Animal weight, hematologic toxicity, tumor volume, and serum calcitonin were monitored for the following 3 mo. Improvement of 125 I-F6 tumor biodistribution by antiangiogenic drug was studied after pretreatment by thalidomide. Follow-up of the tumor after combined antiangiogenic and radioimmunotherapy therapies was performed by histology studies. Results: Combined associations, as compared with radioimmunotherapy alone, increased leukopenia but not thrombocytopenia. Tumor volume-quadrupling time (TVQT) was 22.8 6 3.3 d in the control group, 29.9 6 3.6 d in the group treated with thalidomide, 34.6 6 4.4 d in the group treated with CBOP11, and 51.0 6 2.8 d after radioimmunotherapy alone. As compared with radioimmunotherapy, TVQT was significantly longer (P , 0.01) after thalidomide followed by radioimmunotherapy (69.83 6 3.9), CBOP11 followed by radioimmunotherapy (71.3 6 6.1), and CBOP11-radioimmunotherapy in concomitance (64.2 6 6.1). Nevertheless, TVQT was not increased after radioimmunotherapy followed by thalidomide (48.8 6 4) and radioimmunotherapy followed by CBOP11 (56.8 6 4.8). Surprisingly, pretreatment by CBOP11 or thalidomide sensitized larger tumors (.300 mm 3 ) to radioimmunotherapy. Change in calcitonin levels confirmed morphologic tumor response. Tumor uptake 24 h after injection of 125 I-F6 was 4.5 6 0.6 percentage injected dose per gram (%ID/g) without pretreatment and 8.7 6 1.3 %ID/g with pretreatment by thalidomide. An increase of the antitumor effect observed using the antiangiogenic drug combined with radioimmunotherapy was correlated with a decrease of blood vessels shown by von Willebrand immunostaining. Conclusion: Pretreatment with antiangiogenic therapies improved radioimmunotherapy efficacy, with acceptable toxicity. Future investigations will be performed to understand how antia...