A pilot study of short-course intensive multiagent chemotherapy in metastatic and axial skeletal osteosarcoma.
BACKGROUND
This pilot study was undertaken to assess the feasibility, toxicity and response to short-course multiagent chemotherapy followed by high-dose chemotherapy (HDC) in patients with poor prognosis osteosarcoma.


METHODS
A total of 30 patients entered the study. Chemotherapy consisted of four blocks of multiagent chemotherapy administered sequentially over a short period in a dose-intensive manner. This therapy was followed by HDC which consisted of carboplatin at an AUC8 x 3 days, etoposide 400 mg/m(2) x 3 days and cyclophosphamide 60 mg/kg x 2 days.


RESULTS
A total of 227 cycles of chemotherapy were administered. The main toxicity (for blocks 1-4) was haematological. There were two treatment-related deaths: one post HDC due to sepsis and one during surgery. High-dose chemotherapy was administered to 11 patients (10 with extremity tumours and only one with a pelvic tumour). Twenty-seven patients underwent surgery to the primary. Histological response was assessed in 23 patients. Seven patients (30%) had >90% necrosis. Eight patients underwent pulmonary metastatectomy. The median survival time for the whole group was 16 months. The 2- and 3-year survival rates were 50% and 21% for those with extremity tumours and 19% and 13% for those with axial skeletal tumours.


CONCLUSIONS
Dose-intensive multiagent chemotherapy though feasible in the group of patients with extremity tumours did not significantly improve the treatment outcome compared with conventional relapse therapy. Inferior survival rates in the axial skeletal group are attributed to less intensive treatment and poor local tumour control.
Janinis
J
J
Meyerstein Institute of Oncology, Middlesex Hospital, London.
McTiernan
A
A
Driver
D
D
Mitchell
C
C
Cassoni
A M
AM
Pringle
J
J
Kilby
A
A
Whelan
J S
JS
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001707:Biopsy, Needle; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D010865:Pilot Projects; D011379:Prognosis; D018570:Risk Assessment; D012494:Sampling Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate