A phase II study of cisplatin, doxorubicin, and ifosfamide with peripheral blood stem cell support in patients with skeletal osteosarcoma and variant bone tumors with a poor prognosis.
BACKGROUND
The authors evaluated the efficacy and toxicity of cisplatin, ifosfamide, and doxorubicin with peripheral blood stem cell (PBSC) support in adult patients with osteosarcomas and variants with a poor prognosis.


METHODS
Between December 1994 and January 2001, 37 patients (20 males and 17 females) with a median age of 38 years (range, 18-63 years) entered the study. Ten patients had pelvic osteosarcomas (OS), 6 had malignant fibrous histiocytomas, 5 had metastatic OS, and 16 had miscellaneous histologies. The authors used doxorubicin (60-75 mg/m(2)) and ifosfamide (10 g/m(2)) followed by granulocyte-colony-stimulating factor (G-CSF) (5 microg/kg twice per day) for mobilization of PBSC, collected at a median of 12 days (range, 10-14 days). Three cycles with cisplatin (120 mg/m(2)), ifosfamide (10 g/m(2)), and doxorubicin (75 mg/m(2)), given 28 days apart, were planned followed by PBSC (2-4 x 10(6) CD34-positive cells/kg) infusion plus G-CSF.


RESULTS
Patients received a median of three cycles (range, one to three cycles) in addition to the mobilizing cycle. The median PBSC collection was 17.5 x 10(6)/kg (range, 13.2-90.8 x 10(6)/kg) with a median of 1 apheresis (range, 1-2 aphereses). Twenty-eight patients underwent surgery, 10 achieved 95-100% necrosis, and 4 achieved 90-94% necrosis. Six patients required early discontinuation of therapy due to toxicities, two patients developed progressive disease, and one patient was deemed unresectable. The median time to progression (TTP) and overall survival by Kaplan-Meier estimates for all 37 patients was 19 months and 49 months, respectively.


CONCLUSIONS
The authors accomplished the objective of improving the rate of necrosis with intensification of preoperative therapy. However, TTP and survival rates remained poor. The toxicity profile of this regimen is prohibitive and alternative strategies need to be investigated.
Patel
Shreyaskumar R
SR
The Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, PO Box 450, 1515 Holcombe Boulevard, Houston, TX 77030, USA. spatel@mdanderson.org
Papadopolous
Nicholas
N
Raymond
A Kevin
AK
Donato
Michele
M
Seong
Chu-Myong
CM
Yasko
Alan W
AW
Lewis
Valerae O
VO
Lin
Patrick P
PP
Champlin
Richard
R
Benjamin
Robert S
RS
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide