scholarly journals Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non–High-Dose Methotrexate–Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center

2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jyoti Bajpai ◽  
Arun Chandrasekharan ◽  
Vijai Simha ◽  
Vikas Talreja ◽  
Ashay Karpe ◽  
...  
Keyword(s):  
International Standards ◽  
High Dose ◽  
The Novel ◽  
High Dose Methotrexate ◽  
Histologic Response ◽  
Term Survival ◽  
Dose Methotrexate ◽  
Metastatic Osteosarcoma ◽  
Treatment Naïve ◽  
Dose Dense

Purpose Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)–based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX–based regimen is worth exploring, especially in India and low- and middle-income countries. Materials and Methods All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected. Results Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis. Conclusion The novel, low-cost, non-HDMTX–based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.

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

1984 ◽  
Vol 2 (3) ◽  
pp. 152-156 ◽  
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.

Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1766-1775 ◽  
Author(s):  
G Saeter ◽  
T A Alvegård ◽  
I Elomaa ◽  
A E Stenwig ◽  
T Holmström ◽  
...  
Keyword(s):  
Preoperative Chemotherapy ◽  
Single Agent ◽  
High Dose ◽  
Preoperative Treatment ◽  
High Dose Methotrexate ◽  
Histologic Response ◽  
Dose Methotrexate ◽  
High Grade Osteosarcoma ◽  
The Individual ◽  
Grade Iii

From 1982 to 1989, 97 patients with extremity-localized, high-grade osteosarcoma were treated according to the T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (Cancer 49:1221-1230, 1991). Observed histologic response was no certain chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative cisplatin/doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial chemotherapy effect is important for the final outcome in osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for tumor response, suggesting a dose-response relationship for HD MTX treatment.

scholarly journals Complete Radiologic Response and Long-Term Survival With Use of Systemic High-Dose Methotrexate for Breast Cancer–Associated Leptomeningeal Disease

2012 ◽  
Vol 12 (6) ◽  
pp. 445-449 ◽  
Author(s):  
Cesar A. Santa-Maria ◽  
Ashley Cimino-Mathews ◽  
Kendall F. Moseley ◽  
Antonio C. Wolff ◽  
Jaishri O. Blakeley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Leptomeningeal Disease ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Term Survival ◽  
Long Term Survival ◽  
Dose Methotrexate

Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

1998 ◽  
Vol 16 (2) ◽  
pp. 658-663 ◽  
Author(s):  
G Bacci ◽  
S Ferrari ◽  
N Delepine ◽  
F Bertoni ◽  
P Picci ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Complete Response ◽  
Primary Chemotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Histologic Response ◽  
Histologic Subtype ◽  
Dose Methotrexate ◽  
Serum Peak ◽  
Localized Disease

PURPOSE In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy. PATIENTS AND METHODS In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response. RESULTS Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%). CONCLUSION Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

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