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. 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
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

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

slide13

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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