Phase 1 study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response.
BACKGROUND
To determine the safety and maximum-tolerated dose of concurrent sunitinib and image-guided radiotherapy (IGRT) followed by maintenance sunitinib in oligometastastic patients.


METHODS
Eligible patients had 1 to 5 sites of metastatic cancer measuring<or=6 cm. The most common treatment sites were bone, liver, and lung. Patients were treated with concurrent sunitinib (Day 1 through Day 28) and IGRT (40-50 Gy in 10 fractions starting on Day 8) followed by maintenance sunitinib (50 mg daily, 4 weeks on/2 weeks off starting on Day 43). The starting dose was sunitinib 25 mg and IGRT 40 Gy. Doses were escalated in a ping-pong design with incremental increases in either sunitinib or IGRT.


RESULTS
Twenty-one patients with 36 metastatic lesions were enrolled, with a median follow-up of 10 months. No dose limiting toxicities (DLT) were noted at dose levels 1 or 2 (SU 37.5 mg/RT 40 Gy). One of 10 patients at dose level 3 (SU 37.5 mg/RT 50 Gy) and 2 of 5 patients at dose level 4 (SU 50 mg/RT 50 Gy) experienced DLTs comprising grade 4 myelosuppression and grade 3 nausea. At last follow-up, 8 patients are alive without evidence of progression. The 1-year local, progression-free, and overall survival were 85%, 44%, and 75%, respectively.


CONCLUSIONS
Addition of SU (25 to 37.5 mg) to IGRT is tolerable in patients with oligometastases, without potentiation of RT toxicity. On the basis of promising antitumor responses observed with this novel combination, a multi-institutional phase 2 trial using SU 37.5 mg/RT 50 Gy is ongoing.
Kao
Johnny
J
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA. johnny.kao@mountsinai.org
Packer
Stuart
S
Vu
Ha Linh
HL
Schwartz
Myron E
ME
Sung
Max W
MW
Stock
Richard G
RG
Lo
Yeh-Chi
YC
Huang
Delphine
D
Chen
Shu-Hsia
SH
Cesaretti
Jamie A
JA
D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000532:radiotherapy*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D010349:Patient Compliance; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D011829:Radiation Dosage; D000077210:Sunitinib
D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib