Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma
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INCIDENCE OF DELAYS IN CHEMOTHERAPY DUE TO METHOTREXATE TOXICITY IN TREATMENT OF OSTEOSARCOMA PowerPoint PPT Presentation


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INCIDENCE OF DELAYS IN CHEMOTHERAPY DUE TO METHOTREXATE TOXICITY IN TREATMENT OF OSTEOSARCOMA. M. Perisoglou, B. Seddon, S. Daniels, N. Mayne, J. Whelan Department of Oncology University College Hospital, London, UK. HIGH-DOSE METHOTREXATE IN TREATMENT OF OSTEOSARCOMA.

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INCIDENCE OF DELAYS IN CHEMOTHERAPY DUE TO METHOTREXATE TOXICITY IN TREATMENT OF OSTEOSARCOMA

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Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma

INCIDENCE OF DELAYS IN CHEMOTHERAPY DUE TO METHOTREXATE TOXICITY IN TREATMENT OF OSTEOSARCOMA

M. Perisoglou, B. Seddon, S. Daniels, N. Mayne, J. Whelan

Department of Oncology

University College Hospital, London, UK

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


High dose methotrexate in treatment of osteosarcoma

HIGH-DOSE METHOTREXATE IN TREATMENT OF OSTEOSARCOMA

  • High-dose methotrexate (12 gr/m2): essential component of osteosarcoma treatment

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


High dose methotrexate in treatment of osteosarcoma1

HIGH-DOSE METHOTREXATE IN TREATMENT OF OSTEOSARCOMA

  • High-dose methotrexate (12 gr/m2): essential component of osteosarcoma treatment

  • Supportive measures

    - iv hydration

    - urinary alkalinisation

    - folinic acid rescue (pharmacokinetically guided)

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


High dose methotrexate in treatment of osteosarcoma2

HIGH-DOSE METHOTREXATE IN TREATMENT OF OSTEOSARCOMA

  • High-dose methotrexate (12 gr/m2): essential component of osteosarcoma treatment

  • Supportive measures

    - iv hydration

    - urinary alkalinisation

    - folinic acid rescue (pharmacokinetically guided)

  • Methotrexate tolerance

    There is wide intra- and inter-patient variation to MTX tolerance, primary determinant of which appears to be variation in the pharmacokinetics of the drug

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methotrexate toxicity

METHOTREXATE TOXICITY

  • Mucositis / Stomatitis

  • Bone marrow suppression

  • Nephrotoxicity

  • Hepatotoxicity

  • Dermatitis

  • Encephalopathy

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methotrexate toxicity1

METHOTREXATE TOXICITY

  • Mucositis / Stomatitis

  • Bone marrow suppression

  • Nephrotoxicity

  • Hepatotoxicity

  • Dermatitis

  • Encephalopathy

  • Patient’s discomfort

  • Increased morbidity

  • Increased costs

  • Potentially reduced treatment efficacy

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Delays in chemotherapy and outcome in osteosarcoma

DELAYS IN CHEMOTHERAPY AND OUTCOME IN OSTEOSARCOMA

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Delays in chemotherapy and outcome in osteosarcoma1

DELAYS IN CHEMOTHERAPY AND OUTCOME IN OSTEOSARCOMA

  • Frei at al. Am J Med, 1980

    Chemotherapy response in osteosarcoma improves by increasing MTX dose and worsens by increasing the time between MTX administrations

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Delays in chemotherapy and outcome in osteosarcoma2

DELAYS IN CHEMOTHERAPY AND OUTCOME IN OSTEOSARCOMA

  • Frei at al. Am J Med, 1980

    Chemotherapy response in osteosarcoma improves by increasing MTX dose and worsens by increasing the time between MTX administrations

  • Delepine et al. Cancer, 1996

    Dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localised high grade osteosarcoma

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Delays in chemotherapy and outcome in osteosarcoma3

DELAYS IN CHEMOTHERAPY AND OUTCOME IN OSTEOSARCOMA

  • Frei at al. Am J Med, 1980

    Chemotherapy response in osteosarcoma improves by increasing MTX dose and worsens by increasing the time between MTX administrations

  • Delepine et al. Cancer, 1996

    Dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localised high grade osteosarcoma

  • French Tumour Study Group, Cancer, 1998

    Delay in MTX course administration is a negative prognostic factor in osteosarcoma

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Delays in chemotherapy and outcome in osteosarcoma4

DELAYS IN CHEMOTHERAPY AND OUTCOME IN OSTEOSARCOMA

  • Frei at al. Am J Med, 1980

    Chemotherapy response in osteosarcoma improves by increasing MTX dose and worsens by increasing the time between MTX administrations

  • Delepine et al. Cancer, 1996

    Dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localised high grade osteosarcoma

  • French Tumour Study Group, Cancer, 1998

    Delay in MTX course administration is a negative prognostic factor in osteosarcoma

  • Bacci et al. Oncol Rep, 2001

    Avoiding reductions in MTX doses and /or delays in chemotherapy is crucial in osteosarcoma outcome

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma

MAP (Methotrexate + Adriamycin+ cisPlatin)

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Objectives and methods

OBJECTIVES AND METHODS

  • OBJECTIVE

    Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Objectives and methods1

OBJECTIVES AND METHODS

  • OBJECTIVE

    Incidence of delays in chemotherapy due to methotrexate toxicity in treatment of osteosarcoma

  • METHODS

    - Patients treated with MAP between 2003 and January 2006

    - Notes of 56 patients retrieved

    - Data collected on age, gender, chemotherapy dates, surgery dates, folinic acid rescue

    - Delayed courses identified, information collected on delays due to MTX toxicity

    - Applicable and non-applicable cycles

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Folinic acid rescue far regimens

FOLINIC ACID RESCUE (FAR) REGIMENS

  • FAR regimen A

    - FAR starts at 24 hours and continues until MTX serum levels <0.2 µmol/L

    - FAR is adjusted according to MTX levels, 48 hours onwards

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Folinic acid rescue far regimens1

FOLINIC ACID RESCUE (FAR) REGIMENS

  • FAR regimen A

    - FAR starts at 24 hours and continues until MTX serum levels <0.2 µmol/L

    - FAR is adjusted according to MTX levels, 48 hours onwards

  • FAR regimen B

    - FAR starts at 24 hours and continues until MTX serum levels <0.2 µmol/L

    - FAR is adjusted according to MTX levels, 24 hoursonwards

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Folinic acid rescue far regimens2

FOLINIC ACID RESCUE (FAR) REGIMENS

LATE

  • FAR regimen A

    - FAR starts at 24 hours and continues until MTX serum levels <0.2 µmol/L

    - FAR is adjusted according to MTX levels, 48 hours onwards

  • FAR regimen B

    - FAR starts at 24 hours and continues until MTX serum levels <0.2 µmol/L

    - FAR is adjusted according to MTX levels, 24 hoursonwards

EARLY

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods1

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods2

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods3

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods4

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Methods5

METHODS

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Results

RESULTS

  • Total number of patients: 56

  • Median age: 20 years

  • M:F 1.6:1

  • Total number of cycles received: 235

  • Median number of cycles received per patient: 5

  • Applicable cycles: 175 FAR regimen A: 98/175 (56%)

    FAR regimen B: 77/175 (44%)

  • Median number of applicable cycles received per patient: 4

  • Median number of delayed cycles per patient: 1.5

  • No deaths due to MTX toxicity

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delayed chemotherapy cycles

INCIDENCE OF DELAYED CHEMOTHERAPY CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delayed chemotherapy cycles1

INCIDENCE OF DELAYED CHEMOTHERAPY CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delayed chemotherapy cycles2

INCIDENCE OF DELAYED CHEMOTHERAPY CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delayed chemotherapy cycles3

INCIDENCE OF DELAYED CHEMOTHERAPY CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Mtx induced delays in chemotherapy

MTX-INDUCED DELAYS IN CHEMOTHERAPY

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Incidence of delays per cycle

INCIDENCE OF DELAYS PER CYCLE

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Age and delayed cycles

AGE AND DELAYED CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Age and delayed cycles1

AGE AND DELAYED CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Age and delayed cycles2

AGE AND DELAYED CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Age and delayed cycles3

AGE AND DELAYED CYCLES

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Omitted mtx courses and early discontinuation of map

OMITTED MTX COURSES AND EARLY DISCONTINUATION OF MAP

  • OMITTED MTX COURSES

    - of 350 planned MTX courses, 5% (16/350) were omitted due to MTX toxicity

  • MAP EARLY DISCONTINUATION

    - in 10% (6/56) of the patients MAP treatment was discontinued early due to MTX toxicity

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Conclusions

CONCLUSIONS

  • MTX-induced chemotherapy delays have decreased by ~20% with early FAR adjustment (57% vs 47%)

  • Median number of delayed chemotherapy cycles per patient: 1.5/4

  • Incidence of MTX-induced chemotherapy delays is still high

  • Improving rescue from MTX-toxicity is a worthwhile goal

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


Conclusions1

CONCLUSIONS

  • MTX-induced chemotherapy delays have decreased by ~20% with early FAR adjustment (57% vs 47%)

  • Median number of delayed chemotherapy cycles per patient: 1.5/4

  • Incidence of MTX-induced chemotherapy delays is still high

  • Improving rescue from MTX-toxicity is a worthwhile goal

CTOS, 12th Annual Meeting, Venice 2-4 November 2006


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