Chemotherapy, Irradiation, and Surgery for Function-preserving Curative Therapy of Primary Extremity Soft Tissue Sarcomas: Initial Treatment With I-MAP and Inhalation GM-CSF During Preoperative Irradiation and Postoperatively.
OBJECTIVE
To determine if aerosol granulocyte macrophage-colony-stimulating factor (GM-CSF) decreases the 2-year pulmonary metastasis rate for soft tissue sarcoma.


METHODS
Patients with high-grade soft tissue sarcomas were treated with 2 cycles of ifosfamide, mitomycin, doxorubicin, and cisplatin plus GM-CSF subcutaneous followed by 45 Gy irradiation with concurrent 2 cycles of mitomycin, doxorubicin, and cisplatin followed by surgery +/- intraoperative radiation or brachytherapy. Aerosol GM-CSF (250 mcg twice a day) was administered for 1 week every other week 3× during neoadjuvant therapy and beginning 4 weeks postoperatively every other week 5×.


RESULTS
A total of 39 patients were enrolled between November 2001 and April 2006. The median age was 51 years (range, 19 to 65 y). The median lesion size was 9 cm (range, 2.3 to 26.7 cm). Seventy-six percent experienced grade 3-4 hematologic toxicity. Twenty-four of the first 35 evaluable patients (69%; 95% CI, 41%-84%) were free of pulmonary metastasis at 2 years. A total of 82% (95% CI, 70%-95%) of patients were still alive after 3 years, with a median follow-up of 5.5 years (range, 3.4 to 7.6 y). A total of 58% (95% CI, 44%-76%) of patients remained progression free after 3 years.


CONCLUSIONS
The addition of aerosol GM-CSF to combined chemotherapy, irradiation, and surgery for soft tissue sarcomas did not achieve the study endpoint to decrease the 2-year pulmonary metastasis rate.
Departments of *Oncology †Radiation Oncology ‡Orthopedics §Biostatistics ∥Division of Hematology/Oncology, Mayo Clinic, Rochester, MN.
Scott
S
Okuno
Ivy
I
Petersen
Thomas
T
Shives
Michelle
M
Mahoney
Michael
M
Haddock
Franklin
F
Sim
Mary I
MI
O'Connor
Svetomir N
SN
Markovic
William
W
Maples
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage; D005121:Extremities / Q000473:pathology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000453:epidemiology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011184:Postoperative Period; D011878:Radiotherapy / Q000379:methods; D012509:Sarcoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D055815:Young Adult
D016685:Mitomycin; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D007069:Ifosfamide