Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS)

Schlemmer, M.; Wendtner, Clemens-M.; Lindner, Lars H.; Abdel-Rahman, S.; Hiddemann, Wolfgang; Issels, Rolf D.

doi:10.3109/02656730903335995

Cited by 12 publications

(14 citation statements)

References 31 publications

(29 reference statements)

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“…We developed thermally sensitive liposomes (Dox-TSLs) that rapidly release doxorubicin in response to 40-42°C heat (14-20). Preclinical work demonstrated tumor drug levels up to 30 times higher than free drug and 3-5 times greater than traditional liposomes; the enhanced delivery was linked to superior anti-tumor efficacy (15, 21).…”

Section: Introductionmentioning

confidence: 99%

Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors

et al. 2012

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Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The EPR effect (Enhanced Permeability and Retention) can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Further, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial anti-tumor efficacy and is in human trials. Here, we demonstrate that thermally sensitive liposomes release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream.

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Section: Introductionmentioning

confidence: 99%

Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors

et al. 2012

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“…Radiotherapy at the AMC typically consisted of 32 Gy in 8 fractions given twice per week over a period of 4 weeks; at the BVI, patients received 36 Gy in 12 fractions given 4 times per week. The radiation techniques applied were similar to the standard techniques used for the treatment of recurrent breast cancer, usually photons (6 MV or 10 MV) for the lateral chest wall, axillary, and periclavicular area and electrons (8)(9)(10)(11)(12)(13)(14)(15) MeV) for the anterior chest wall. Hyperthermia was given once per week within 1 hour of radiotherapy at AMC or twice weekly at BVI (Tables 3 and 4).…”

Section: Methodsmentioning

confidence: 99%

“…It is known that hyperthermia enhances the effect of radiation and/or chemotherapy, particularly in hypoxic areas. [9][10][11] Hyperthermia is used frequently to boost the relatively low maximally permitted radiotherapy dose in the treatment of recurrences of breast cancer in previously irradiated areas. [12][13][14] In total, 16 patients with RAS received RT-HT at our institutes.…”

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confidence: 99%

Reirradiation and hyperthermia for radiation‐associated sarcoma

Jong

Oldenborg

Oei

et al. 2011

Cancer

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BACKGROUND:The objective of this study was to evaluate the role of reirradiation and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the thoracic region, which is an increasing, yet extremely rare condition with a poor prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic region were treated in the Academic Medical Center and the Institute Verbeeten with reirradiation and hyperthermia. In 13 patients, this treatment was given for unresectable disease and 3 times after resection as adjuvant treatment. The median latency period between the original malignancy diagnosis and the RAS diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11 patients (69%). The literature on reirradiation with or without hyperthermia for RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204 months). Four patients were not evaluable for response. The response rate for the remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six patients remained free of local failure until death (5 months and 7 months) or last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The current study indicates that combined reirradiation and hyperthermia for RAS in the thoracic region is feasible. The high response rate and the possibility of durable local control suggest that this treatment is promising. Cancer 2012;118:180-

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“…Further, overall survival was better in the combined arm (HR 0.66;p=0.038). Although there have been other phase II trials of this combination treatment, few centers have adopted the approach (Schlemmer et al, 2010). At present, the potential benefits of this new intervention are restricted to patients with very high-risk soft tissue sarcomas in the context of a clinical trial.…”

Section: Neoadjuvant Chemotherapy and Regional Hyperthermiamentioning

confidence: 99%

Neoadjuvant Chemotherapy for Soft Tissue Sarcoma of the Extremity or Trunk, Gastrointestinal Stromal Tumors, and Retroperitoneal Sarcoma

Mack¹,

Temple²

2012

Neoadjuvant Chemotherapy - Current Applications in Clinical Practice

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Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS)

Abstract: Response to combined modality treatment with RHT and neoadjuvant chemotherapy was predictive for an improved LFFS and led to limb preservation in 79% of patients with extremity sarcomas.

Cited by 12 publications

References 31 publications

Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors

Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors

Reirradiation and hyperthermia for radiation‐associated sarcoma

Neoadjuvant Chemotherapy for Soft Tissue Sarcoma of the Extremity or Trunk, Gastrointestinal Stromal Tumors, and Retroperitoneal Sarcoma

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