Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.

Carli, Modesto; Pastore, Guido; Perilongo, Giorgio; Grotto, Paolo; Bernardi, Bruno; Ceci, Adriana; Tullio, Marco Di; Madon, E; Pianca, C.; Paolucci, G

doi:10.1200/jco.1988.6.4.654

Cited by 26 publications

(12 citation statements)

References 4 publications

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“…Second, Act D has been used in the clinic for more than 40 years in the treatment of rare cancers in children and young adults (36). Third, Act D is effective in the clinic without untoward toxicity (41). Fourth, adults treated with 10–15 μg/kg Act D achieved peak plasma levels of 0.01–0.1 μg/mL, and children treated with 0.75–1.50 mg/m 2 Act D obtained peak plasma levels ranging from 0.02–0.05 μg/mL (36, 42).…”

Section: Discussionmentioning

confidence: 99%

Transcription Inhibition of Heat Shock Proteins: A Strategy for Combination of 17-Allylamino-17-Demethoxygeldanamycin and Actinomycin D

2009

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The heat shock protein (HSP) 90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical trials because of its unique mechanism of action and antitumor activity. However, 17-AAG triggers the transcription and elevation of antiapoptotic HSP90, HSP70, and HSP27, which lead to chemoresistance in tumor cells. We hypothesized that inhibiting HSP90, HSP70, and HSP27 transcription may enhance 17-AAG-induced cell death in multiple myeloma cell lines. Actinomycin D (Act D), a clinically used agent and transcription inhibitor, was combined with 17-AAG. The concentrations for 17-AAG and Act D were selected based on the target actions and plasma levels during therapy. Inducible and constitutive HSP27, HSP70, and HSP90 mRNA and protein levels were measured by real-time reverse transcription-PCR and immunoblot assays. Compared with no treatment, Act D alone decreased HSP mRNA levels in MM.1S and RPMI-8226 cell lines. Combining Act D with 17-AAG did not attenuate 17-AAG-mediated increases in transcript levels of inducible HSP70; however, constitutive HSP mRNA levels were decreased. In contrast to its effect on mRNA levels, Act D was able to abrogate 17-AAG-mediated increases in all HSP protein levels. The cytotoxicity of combined Act D and 17-AAG was assessed. Treatment with Act D alone caused <40% cell death, whereas the combination of 17-AAG and Act D resulted in an increase of cell death in both multiple myeloma cell lines. In conclusion, these results indicate that 17-AAG-mediated induction of HSP70 and HSP27 expression can be attenuated by Act D and therefore can potentially improve the clinical treatment of multiple myeloma. [Cancer Res 2009;69(9):3947-54]

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Section: Discussionmentioning

confidence: 99%

Transcription Inhibition of Heat Shock Proteins: A Strategy for Combination of 17-Allylamino-17-Demethoxygeldanamycin and Actinomycin D

2009

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“…Treatment has been described elsewhere [6]. Patients were treated according to their IRS grouping at the time of registration.…”

Section: Methodsmentioning

confidence: 99%

Long‐term results in childhood rhabdomyosarcoma: A report from the Italian cooperative study RMS 79

Bisogno

Pastore

Perilongo

et al. 2011

Pediatric Blood & Cancer

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BackgroundThe results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long‐term survival can be expected, but late events are known to occur. We analyzed the long‐term results of the RMS 79 protocol to investigate the type and impact of such events.ProcedureFrom 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow‐up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone.ResultsOverall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment‐related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long‐term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group.ConclusionsMajor late events can significantly affect the long‐term survival of children with RMS. Modern protocols should provide for a much longer follow‐up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated. Pediatr Blood Cancer 2012; 58: 872–876. © 2011 Wiley Periodicals, Inc.

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“…10-20%. In one study where response in Groups III/IV patients was assessed after -8 weeks CVAct, CR + PR rate = 54% (Carli et al, 1988). For these two groups the response rate with Rapid VAC was 78% suggesting there may be some advantage to this schedule.…”

Section: Methodsmentioning

confidence: 99%

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas

Pinkerton

Groot-Loonen²,

Barrett³

et al. 1991

Br J Cancer

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Summary Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with a rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour.The Rapid VAC regimen was well tolerated and largely administered as an out-patient. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.

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Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.

Cited by 26 publications

References 4 publications

Transcription Inhibition of Heat Shock Proteins: A Strategy for Combination of 17-Allylamino-17-Demethoxygeldanamycin and Actinomycin D

Transcription Inhibition of Heat Shock Proteins: A Strategy for Combination of 17-Allylamino-17-Demethoxygeldanamycin and Actinomycin D

Long‐term results in childhood rhabdomyosarcoma: A report from the Italian cooperative study RMS 79

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas

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