scholarly journals Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma.Pre-surgical treatment of primary tumor and of overt pulmonary metastases

Cancer ◽  
1977 ◽  
Vol 39 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Norman Jaffe ◽  
Emil Frei ◽  
Demetrius Traggis ◽  
Hugh Watts
Keyword(s):  
Surgical Treatment ◽  
Primary Tumor ◽  
Pulmonary Metastases ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy.

1983 ◽  
Vol 1 (4) ◽  
pp. 251-254 ◽  
Author(s):  
N Jaffe ◽  
E Smith ◽  
H T Abelson ◽  
E Frei
Keyword(s):  
Adjuvant Chemotherapy ◽  
Median Time ◽  
Pulmonary Metastases ◽  
Osteogenic Sarcoma ◽  
Median Number ◽  
Control Group ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Age And Sex

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.

Weekly high-dose methotrexate and doxorubicin for osteosarcoma: the Dana-Farber Cancer Institute/the Children's Hospital--study III.

1987 ◽  
Vol 5 (8) ◽  
pp. 1178-1184 ◽  
Author(s):  
A M Goorin ◽  
A Perez-Atayde ◽  
M Gebhardt ◽  
J W Andersen ◽  
R H Wilkinson ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Lymphocytic Infiltration ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Dana Farber Cancer Institute ◽  
Dose Methotrexate ◽  
Leucovorin Rescue ◽  
Hospital Study

Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).

Carboplatin/Ifosfamide Window Therapy for Osteosarcoma: Results of the St Jude Children’s Research Hospital OS-91 Trial

2001 ◽  
Vol 19 (1) ◽  
pp. 171-182 ◽  
Author(s):  
William H. Meyer ◽  
Charles B. Pratt ◽  
Catherine A. Poquette ◽  
Bhaskar N. Rao ◽  
David M. Parham ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Primary Tumor ◽  
Pilot Trial ◽  
Disease Rate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Chemotherapy Protocol ◽  
Multiagent Chemotherapy

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m2 × 1) and ifosfamide (2.65 g/m2/d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma.

1985 ◽  
Vol 3 (8) ◽  
pp. 1101-1104 ◽  
Author(s):  
N Jaffe ◽  
R Robertson ◽  
A Ayala ◽  
S Wallace ◽  
V Chuang ◽  
...  
Keyword(s):  
Partial Response ◽  
Alternative Treatment ◽  
Primary Tumor ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Primary Osteosarcoma ◽  
To Receive ◽  
Pathologic Parameters

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Short Latency ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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