High-dose methotrexate and HELP [Holoxan (ifosfamide), eldesine (vindesine), platinum]--doxorubicin in non-metastatic osteosarcoma of the extremity: a French multicentre pilot study. Fédération Nationale des Centres de Lutte contre le Cancer and Société Française d'Oncologie Pédiatrique.
This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery.


METHODS
Sixty-two patients (39 males, 23 females: median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)-doxorubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP-doxorubicin.


RESULTS
Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery; histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30-80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome.


CONCLUSIONS
This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.
Philip
T
T
Centre Léon-Bérard, Pediatric and Medical Oncology Departement, Lyon, France. Philip@lyon.fnclcc.fr
Iliescu
C
C
Demaille
M C
MC
Pacquement
H
H
Gentet
J C
JC
Krakowski
I
I
Soler-Michel
P
P
Thiesse
P
P
Chauvin
F
F
Blay
J Y
JY
Brunat-Mentigny
M
M
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005602:France; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity; D009336:Necrosis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate; D013997:Time Factors; D014751:Vindesine / Q000008:administration & dosage / Q000633:toxicity
D004317:Doxorubicin; D002945:Cisplatin; D014751:Vindesine; D007069:Ifosfamide; D008727:Methotrexate