Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03)

TY - JOUR

T1 - Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03)

AU - Jakob, Jens

AU - Simeonova, Anna

AU - Kasper, Bernd

AU - Ronellenfitsch, Ulrich

AU - Rauch, Geraldine

AU - Wenz, Frederik

AU - Hohenberger, Peter

PY - 2016/6/3

Y1 - 2016/6/3

N2 - BACKGROUND: Experimental data demonstrated that concurrent anti-angiogenic treatment with sunitinib may improve the efficacy of radiation therapy (RT). Here we report the results of a phase I trial performed within the German Interdisciplinary Sarcoma Group (GISG-03) of combined sunitinib and RT for neoadjuvant treatment of locally advanced soft tissue sarcoma (STS).METHODS: The primary endpoint of the study was to explore the recommended dose of sunitinib combined with RT for subsequent trials. Treatment response, postoperative complications after tumor resection and toxicity according to CTCAE 4.0 were secondary endpoints. The study used a 3 + 3 design. Patients received either 25 mg (dose level 1) or 37.5 mg (dose level 2) sunitinib two weeks prior to and throughout RT (28 × 1.8 Gy). Surgery was scheduled 5-8 weeks after completion of neoadjuvant treatment.STUDY REGISTRATION: NCT01498835.RESULTS: Six patients were enrolled in dose level 1 and three patients in dose level 2. Median tumor size was 11 cm. Tumors were located in the retroperitoneum (4/9), lower leg (3/9) or trunk (2/9). At dose level 1, 1/6 patients developed dose limiting lymphopenia. At dose level 2, no patient developed dose limiting toxicity. Most frequent toxicities were hematological (8/9) and oral (5/9). Dose adjustments of sunitinib were necessary in 5/9 patients. All patients received full dose RT and underwent tumor resection (8/9 R0 and 1/9 R1). Local toxicity of RT did not exceed Grade 2. 2/9 patients had postoperative complications requiring re-intervention. Treatment response according to RECIST was as follows: partial response 1/9, stable disease 7/9, and progressive disease 1/9. Pathological examination revealed ≥ 95 % tumor necrosis in 3/9 resected specimens.CONCLUSIONS: Combined sunitinib and RT was tolerable as neoadjuvant treatment for locally advanced STS patients regardless of tumor localization. The recommended sunitinib dose for subsequent trials is 37.5 mg.

AB - BACKGROUND: Experimental data demonstrated that concurrent anti-angiogenic treatment with sunitinib may improve the efficacy of radiation therapy (RT). Here we report the results of a phase I trial performed within the German Interdisciplinary Sarcoma Group (GISG-03) of combined sunitinib and RT for neoadjuvant treatment of locally advanced soft tissue sarcoma (STS).METHODS: The primary endpoint of the study was to explore the recommended dose of sunitinib combined with RT for subsequent trials. Treatment response, postoperative complications after tumor resection and toxicity according to CTCAE 4.0 were secondary endpoints. The study used a 3 + 3 design. Patients received either 25 mg (dose level 1) or 37.5 mg (dose level 2) sunitinib two weeks prior to and throughout RT (28 × 1.8 Gy). Surgery was scheduled 5-8 weeks after completion of neoadjuvant treatment.STUDY REGISTRATION: NCT01498835.RESULTS: Six patients were enrolled in dose level 1 and three patients in dose level 2. Median tumor size was 11 cm. Tumors were located in the retroperitoneum (4/9), lower leg (3/9) or trunk (2/9). At dose level 1, 1/6 patients developed dose limiting lymphopenia. At dose level 2, no patient developed dose limiting toxicity. Most frequent toxicities were hematological (8/9) and oral (5/9). Dose adjustments of sunitinib were necessary in 5/9 patients. All patients received full dose RT and underwent tumor resection (8/9 R0 and 1/9 R1). Local toxicity of RT did not exceed Grade 2. 2/9 patients had postoperative complications requiring re-intervention. Treatment response according to RECIST was as follows: partial response 1/9, stable disease 7/9, and progressive disease 1/9. Pathological examination revealed ≥ 95 % tumor necrosis in 3/9 resected specimens.CONCLUSIONS: Combined sunitinib and RT was tolerable as neoadjuvant treatment for locally advanced STS patients regardless of tumor localization. The recommended sunitinib dose for subsequent trials is 37.5 mg.

KW - Adult

KW - Aged

KW - Antineoplastic Agents

KW - Chemoradiotherapy

KW - Cohort Studies

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Indoles

KW - Male

KW - Middle Aged

KW - Neoadjuvant Therapy

KW - Neoplasm Staging

KW - Preoperative Care

KW - Prognosis

KW - Pyrroles

KW - Radiotherapy Dosage

KW - Radiotherapy, Intensity-Modulated

KW - Sarcoma

KW - Clinical Trial, Phase I

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/s13014-016-0654-2

DO - 10.1186/s13014-016-0654-2

M3 - SCORING: Journal article

C2 - 27255678

VL - 11

SP - 77

JO - RADIAT ONCOL

JF - RADIAT ONCOL

SN - 1748-717X

ER -