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01.05.2014 | Bone and Soft Tissue Sarcomas | Ausgabe 5/2014

Annals of Surgical Oncology 5/2014

Phase I Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 5/2014
Autoren:
MD Robert J. Canter, MD Dariusz Borys, PhD Abimbola Olusanya, PhD Chin-Shang Li, BA Li-Yuan Lee, MD Robert D. Boutin, MD Scott D. Christensen, MD Robert M. Tamurian, MD, PhD Arta M. Monjazeb
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1245/​s10434-014-3543-7) contains supplementary material, which is available to authorized users.
Presented in part at the Society of Surgical Oncology 65th Annual Cancer Symposium, Orlando, FL, USA, 21–24 March 2012.
Clinical trial information: NCT#00805727.

Abstract

Background

Despite effective local therapy with surgery and radiotherapy (RT), ~50 % of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent.

Methods

For the phase I trial, eight patients with intermediate- or high-grade STS >5 cm in maximal dimension or low-grade STS >8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4–6 weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT).

Results

Eight patients were enrolled in the phase I (five females, median age 44 years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16 cm (range 8–29), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N = 8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥95 % tumor necrosis) was observed in three patients (38 %).

Conclusion

Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).

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Zusatzmaterial
Supplementary material 1 (DOCX 16 kb)
10434_2014_3543_MOESM1_ESM.docx
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