The Role of Methotrexate in Osteosarcoma

Grem, Jean L.; King, Susan A.; Wittes, Robert E.; Leyland‐Jones, Brian

doi:10.1093/jnci/80.9.626

Cited by 49 publications

(24 citation statements)

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“…In the present study, we compared the growth inhibitory potential of PEDF with that of methotrexate, because methotrexate is one of the standard agents currently used in intensive adjuvant chemotherapy regimens for the patients with nonmetastatic osteosarcoma (Grem et al, 1998;Bacci et al, 1998). Methotrexate at the concentrations from 0.3 to 3 AM was reported to significantly inhibit the DNA synthesis in primary tumors derived from patients with osteosarcomas (Mordoh et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells

et al. 2005

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“…There is a considerable body of evidence supporting the role of high-dose methotrexate in the treatment of osteosarcoma since its first use in the 1970s, both as a single agent and as part of multiagent trials (Grem et al, 1988;Rosen, 1993). The advantages of adding high-dose methotrexate to an ifosfamide/etoposide combination include that, individually, it has an impressive single-agent profile; myelotoxic schedules can be resumed after only 1 week of administering HDMTX; and, properly administered, there is minimal toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Ifosfamide and etoposide combinations have been evaluated previously in patients with recurrent paediatric sarcomas (Miser et al, 1987;Goorin et al, 1994;Tabone et al, 1994). High-dose methotrexate has evidence of activity both as a single agent and within multiple agent trials (Grem et al, 1988;Rosen, 1993). Of importance, high-dose methotrexate with folinic acid rescue can be given to neutropenic patients, thereby allowing another agent to be delivered during the myelosuppressive phase of the chemotherapy cycle and thus providing a degree of treatment intensification.…”

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confidence: 99%

Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma

et al. 1999

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Summary Fifteen patients with relapsed osteosarcoma were treated with an intensive combination chemotherapy schedule. Ifosfamide 2.5 g m -2 daily and etoposide 150 mg m -2 daily coincidentally for 3 days and high-dose methotrexate 8 g m -2 (with folinic acid rescue) on days 10-14 in a planned 21-day cycle. Feasibility, toxicity and response to this alternative combination for the treatment of relapsed osteosarcoma was assessed. There were 98 evaluable cycles for toxicity and tolerability. The majority of cycles were well tolerated. Haematological toxicity of grade 3/4 (common toxicity criteria) was seen in all courses. Renal tubular loss of electrolytes, particularly magnesium, occurred in 71% of cycles. Thirteen per cent of cycles were repeated within 21 days and 61% within 28 days. In the thirteen patients evaluable for response, a partial response rate of 31% was seen after two cycles. However, patients with stable disease continued on therapy, and an overall consequent response rate of 62% was observed. Four patients were alive with no evidence of disease at 8-74 months. Three are alive with disease (at 8-19 months). There were six deaths, all disease related. This regimen exhibits an encouraging response rate in a group of children with poor prognosis disease, with a tolerable toxicity profile.

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“…The data reported in the current study indicate that late follow-up should also be reported, and that seasoned results may reflect an accurate appraisal of the true effects of treatment. 35 …”

Section: Discussionmentioning

confidence: 99%

Adjuvant chemotherapy for osteosarcoma of the extremity long-term results of two consecutive prospective protocol studies

Pratt

Champion

Fleming

et al. 1990

Cancer

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Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

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The Role of Methotrexate in Osteosarcoma

Cited by 49 publications

References 0 publications

Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells

Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells

Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma

Adjuvant chemotherapy for osteosarcoma of the extremity long-term results of two consecutive prospective protocol studies

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