Dose response relationship in adult osteosarcoma patients treated with Neo-Adjuvant high dose Methotrexate, surgery and adjuvant chemotherapy

The number and time to appearance of pulmonary metastases were evaluated in 15 patients with osteogenic sarcoma receiving adjuvant chemotherapy with high-dose methotrexate and doxorubicin (adjuvant group). The results were compared to 33 age- and sex-matched controls (control group). The adjuvant group demonstrated a reduction in the number and a delay in the appearance of the metastases. The median time to development of metastases was 17 mo in the adjuvant group and 7 mo in the control group, and the median number of metastases was 2 and 12, respectively.

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A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.1984.2.3.152 ◽

1984 ◽

Vol 2 (3) ◽

pp. 152-156 ◽

Cited By ~ 83

Author(s):

J H Edmonson ◽

S J Green ◽

J C Ivins ◽

G S Gilchrist ◽

E T Creagan ◽

...

Keyword(s):

Pilot Study ◽

Adjuvant Chemotherapy ◽

High Dose ◽

High Dose Methotrexate ◽

Term Survival ◽

Dose Methotrexate ◽

Primary Osteosarcoma ◽

Chemotherapy Patients ◽

One Year

Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised (37 amputations, one limb sparing procedure) were allocated at random to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate (HDMTX) regimen or regular follow-up without primary adjuvant chemotherapy. Although the vincristine, HDMTX, leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2, delayed methotrexate excretion limited dosage escalations in 25%. An estimated 52% of the 38 patients were surviving five years after randomization and an estimated 42% remained continuously relapse-free after five years. No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent; however, power to detect differences was low. Furthermore, no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed. Approximately 20% of these failing patients appear to have been salvaged for long-term survival. This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma.

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Oral steroid-sparing effect of high-dose inhaled corticosteroids in asthma

European Respiratory Journal ◽

10.1183/13993003.01147-2019 ◽

2019 ◽

Vol 55 (1) ◽

pp. 1901147 ◽

Cited By ~ 7

Author(s):

Ingrid Maijers ◽

Nethmi Kearns ◽

James Harper ◽

Mark Weatherall ◽

Richard Beasley

Keyword(s):

Dose Response ◽

Oral Corticosteroid ◽

Inhaled Corticosteroids ◽

Adrenal Suppression ◽

Oral Steroid ◽

Systemic Effects ◽

High Dose ◽

Response Relationship ◽

Dose Response Relationship ◽

Sparing Effect

BackgroundThe proportion of the efficacy of high-dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose–response relationship for oral corticosteroid-sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid-sparing effects due to their systemic effects, based on the comparative dose–response relationship of ICS versus oral corticosteroids on adrenal suppression.MethodsSystematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid-sparing effects of high-dose ICS in oral corticosteroid-dependent asthma. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were retrieved. The primary outcome was the proportion of the oral corticosteroid-sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects.Results11 studies including 1283 participants reporting oral corticosteroid-sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone-sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68–2.08) and for budesonide was 0.93 (95% CI 0.63–1.89).ConclusionIn patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid-sparing effect of high-dose ICS is likely to be due to systemic effects.

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