TDZ Treatment Research Articles

First-Line Treatment of Multiple Myeloma with a Combination of Thalidomide, Dexamethasone, and Zoledronate (TDZ) in an Inner-City Population with High HIV Prevalence.

Background: The combination of thalidomide and dexamethasone is a rescue regimen for multiple myeloma (MM) in relapse, and for pretransplant in newly diagnosed patients. The bisphosphonate zoledronate mitigates bone resorption and possibly tumor growth and angiogenesis. The long-term utility of this combination in a newly diagnosed inner-city MM population with high prevalence of HIV-infection is addressed in this phase II trial. MM is reported with increased frequency in patients with HIV infection, and optimal treatment of MM in these patients is unknown.Methods: Of 30 consecutive enrollees, 22 (16F/6M) were evaluable. Mean age was 61 years (range = 43–82); all had skeletal lesions, and 27% (n = 6) were HIV+ (mean age = 47, range 46–50, all female). Patients received thalidomide 100 mg QD, dexamethasone 10–40 mg PO on Days 1–4, 9–12, and 17–20 monthly for six months, then on Days 1–4 monthly; and zoledronate 4 mg IV monthly, until progression or relapse. Baseline β2-microglobulin indicated high risk for all patients (mean = 6.2 μg/ml, SD = 3.8). At enrollment, 4 patients had AIDS, and 3 were on HAART.Results: Overall response rate (> 50% decrease in M protein) was 72% (n = 13), and 83% (n = 5) in HIV+ patients. In 27% (n = 6), M protein levels were < 0.3 g/dL, including 3 HIV+ patients on HAART. In 23% (n = 5), M protein was reduced by < 50%. Median time to response was 2 months, and mean time on TDZ was 11 months. TDZ treatment decreased serum β2-microglobulin (P <.001). Two patients relapsed, and one patient with HIV and concomitant plasmacytoma did not respond. All three eventually died. Response to treatment was unaffected by HIV status or antiretroviral treatment. Side effects of TDZ were reversible by anticoagulant therapy or dexamethasone reduction.Conclusions: TDZ had significant activity against newly diagnosed MM, suggesting that zoledronate may facilitate response with lower doses of thalidomide. HIV status did not affect response, indicating that this regimen is compatible with concomitant antiretroviral treatment and is equally effective in HIV+ patients. These findings underscore the potential effectiveness of this combination of anti-myeloma agents as a long-term alternative, particularly in patients for whom transplant therapy is not feasible.

First-line, long-term treatment of multiple myeloma with thalidomide, dexamethasone, and zoledronate in combination (TDZ)

6702 Background. Thalidomide + dexamethasone is a rescue regimen for multiple myeloma (MM) in relapse, and for pretransplant in newly diagnosed patients. The bisphosphonate zoledronate mitigates bone resorption and possibly tumor growth and angiogenesis. The long-term utility of this combination in newly diagnosed MM is addressed in this Phase II trial. Methods: Of 26 consecutive enrollees, 19 (15F/4M) were evaluable. Mean age was 59 years (range = 43–76); all had skeletal lesions, 32% (n = 6) were HIV+ (mean age = 46, range 46–50, all female). Patients received thalidomide 100 mg QD, dexamethasone 10–40 mg PO on Days 1–4, 9–12, and 17–20 monthly for six months, then on Days 1–4 monthly; and zoledronate 4 mg IV monthly, until progression or relapse. Baseline β2-microglobulin indicated high risk for all patients (mean = 6.2 μg/ml, SD = 3.8). Results: Overall response rate (> 50% decrease in M protein) is 68 % (n = 13). In 32% (n = 6) M protein levels were < 0.3 g/dL. In 30 % (n = 5) M protein was reduced by < 50%. Median time to response was 2 months, and mean time on TDZ was 11 months. TDZ treatment decreased serum β2-microglobulin (P < .001). One patient did not respond, and two relapsed; all three eventually died. Response to treatment was unaffected by HIV status. Side effects of treatment were reversible by anticoagulant therapy or dexamethasone reduction. Conclusions: TDZ had significant activity against newly diagnosed MM, suggesting that zoledronate may facilitate response with lower doses of thalidomide. HIV status did not affect response. These findings underscore the potential effectiveness of this combination of anti-myeloma agents as a long-term alternative to previously described protocols. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis

Organogênese de explante foliar de clones de Eucalyptus grandis x E. urophylla

O objetivo deste trabalho foi avaliar os efeitos dos reguladores de crescimento TDZ [1-fenil-3-(1,2,3-tia-diazol-5-il)uréia], BAP (6-benzilaminopurina) e ANA (ácido naftalenoacético) no desempenho da propagação in vitro por organogênese de explante foliar de três clones híbridos de Eucalyptus grandis x Eucalyptus urophylla. Houve resposta diferenciada dos clones quanto a intensidade, textura e coloração dos calos, em razão dos tratamentos com os reguladores de crescimento. Os melhores resultados de calejamento dos três genótipos foram observados nos tratamentos com a combinação dos reguladores de crescimento TDZ (0,5 mg L-1) e ANA (0,1 mg L-1), obtendo-se 100% de calejamento no explante foliar. Os piores resultados de calejamento foram observados nos tratamentos com a combinação dos reguladores de crescimento BAP (0,1 mg L-1) e ANA (0,1 mg L-1). Em relação à regeneração, a melhor resposta foi obtida com 1,0 mg L-1 BAP em que 8% dos calos formados a partir de explantes foliares regeneraram gemas, com número médio destas formadas por calo igual a 4,2.

Thidiazuron substitution for chilling requirement in three apple cultivars

Thidiazuron [(TDZ)N-phenyl-N′-1,2,3-thidiazol-5-ylurea] at 750 μM was applied to buds of apple trees to determine if it could substitute for the chilling requirement to induce bud break. Shoots of cv. ‘Anna’ (low chill), ‘Delicious’ cv. Redchief (medium chill), and ‘Northern Spy’ (high chill) were untreated, treated with TDZ prior to chilling (before-chill), and treated with TDZ at various intervals after the accumulation of specific amounts of chilling (after-chill). Shoots were stored in a cold room at 4°C. TDZ applied prior to chilling reduced the chill unit (CU) requirement (1 CU = 1 h at 4°C) for the promotion of bud break on 1-year-old shoots of ‘Anna’ and ‘Northern Spy’ and 1- and 2-year-old wood of ‘Delicious.’ TDZ applied after-chill promoted bud break only for ‘Anna’ and buds on 2-year-old wood of ‘Delicious.’ While accumulating CUs, untreated buds or buds treated with TDZ on 1-year ‘Delicious’ and ‘Northern Spy’ did not respond to the cold treatment even after 1848 h of CU accumulation. For all three cultivars, TDZ treatment was more effective in promoting bud break when applied before the initiation of chilling.