Treatment Regimens

Factors associated with treatments and protocols5

Not all cytotoxic drugs have the same toxicity on the oral mucosa. Table 1 summarises the various treatments associated with an increased risk of oral mucositis. The dose administered and also combination with other drugs in the therapeutic protocol will also increase the risk of mucositis.

Table 1: Treatments associated with an increased risk of oral mucositis

Treatments

 

 

5-FU

Etoposide

Mitomycin

Amsacrine

Fludarabine

Mitotane

Bleomycin

Gefitinib

Mitoxantrone

Carboplatin

Gemcitabine

Paclitaxel

Carmustine

Hydroxyurea

Procarbazine

Chlorambucil

Idarubicin

Streptomycin

Cisplatin

Ifosamide

Sunitinib

Cyclophosphamide

Interferons

Temsirolimus

Cytabarine or Ara-C

Interleukin-2

Thioguanine

Dacarbazine

Irinotecan

Thiotepa

Dactinomycin

Lomustine

Topotecan

Daunorubicin

Mechlorethamine

Tyrosine kinase protein inhibitors

Doxorubicin

Melphalan

Vinblastine

Epirubicin

Mercaptopurine

Vincristine

Erlotinib

Methotrexate (MTX)

Vindesine

Estramustine

Mithramycin

Vinorelbine

Kostler 2001 - The treatments are presented in alphabetical order, and not in order of their relative mucositogenic potential.

Some protocols using high doses of chemotherapy or polychemotherapy have been associated with a high incidence of mucositis:

  • Conditioning for an HSC (haematopoietic stem cell) autograft
  • Conditioning for an HSC (haematopoietic stem cell) allograft
  • Induction phase of the protocol for the treatment of leukaemias and lymphomas
  • In paediatrics43

Table 2

PATHOLOGY

TREATMENT PROTOCOL

Ewing's sarcoma

VIDE (6 courses)

Osteosarcoma

High dose methotrexate (14 courses)

Neuroblastoma

Endoxan/VP16/platinum/vincristine

Burkitt's lymphoma

COPADM

Anaplastic lymphoma

Methotrexate/endoxan/doxorubicin/vinblastine/dexamethasone

Tables 3 and 4 show the main conditioning protocols for autologous and allogenic haematopoietic stem cell (HSC) grafts and also the polychemotherapy for some malignant haemopathies and show the incidence of oral mucositis in these patients.

Table 3: Mucositogenic nature of conditioning protocols for an HSC graft

Protocol (number of patients)

Treatments/dosage

Incidence of mucositis

Reference

Autograft

 

 

 

Melphalan (n=109)

Melphalan iv

Overall: 90%
46% Grades 3-4

Blijlevens N
J Clin Oncol 200810

BEAM (n=88)

BCNU
Cytosine Arabinoside
Etoposide
Melphalan

Overall: 83%
42% Grades 3-4

Blijlevens N
J Clin Oncol 200810

Allograft

 

 

 

Bu-Cy-VP (n=31)

Busulfan
Etoposide
Cyclophosphamide

100% Bearman Grades II-IV*

Zander AR
Clin Cancer Res 199720

TBI-Cy (n=25)

12 Gy radiation for 3 days in 6 fractions -
Cyclophosphamide

96% Bearman Grades I-II*

Kroger N
Bone Marrow Transplant 200119

Radiation

Cyclophosphamide-etoposide-carboplatin (n=35)

2 Gy radiation twice a day: D-8, -7, and -6
Cyclophosphamide
Etoposide
Carboplatin

94% Grades 3-4

Gabriel DA
Biol Blood Marrow Transplant 200521

Bu-Cy (n=69)

Busulfan
Cyclophosphamide

90% Bearman Grades I-II*

Rosenthal MA
Leuk Lymphoma 199422

Gy: gray - iv: intravenous
* Bearman grades:
I - pain and/or ulceration without using morphine iv
II - pain and/or ulceration AND using morphine iv
III - gastric tube
IV - death

Table 4: Examples of cancer protocols and incidence of associated mucositis: hemotological malignancies

Protocol (number of patients)

Treatments/dosage

Incidence of mucositis (Grades)

Reference

Non-Hodgkin's lymphoma (Burkitt)

 

 

 

COPADM,

(MTX 3 g/m²)

LMB 96

Intermediate risk

PREPHASE WITH COP:

Cyclophosphamide

Oncovin (vincristine)

Prednisone

+ methotrexate (MTX) intrathecally (IT)



INDUCTION WITH 2 CONSECUTIVE COPADM:

Cyclophosphamide

Oncovin

Prednisone

Adriamycin doxorubicin

HD* MTX

CONSOLIDATION WITH 2 CYM:

Cytarabine + IT cytarabine

HD MTX

MAINTENANCE:

Cyclophosphamide

Oncovin

Prednisone

HD MTX + IT MTX

COPADM1:

43% (3-4)


COPADM2:

42% (3-4)


M1:

14% (3-4

Patte C

Blood 200723

COPADM,

(MTX 8 g/m²)

LMB 96

High risk

PREPHASE WITH COP:

Idem



INDUCTION WITH 2 CONSECUTIVE COPADM:

Cyclophosphamide

Oncovin

Prednisone

Adriamycin doxorubicin

HD + IT MTX



CONSOLIDATION WITH 2 CYVE:

Cytarabine

HD Ara-C

Etoposide



MAINTENANCE, 4 cycles (M1-M4):

dt M1: COP + MTX

Overall:

81% (3-4)


COP:

5% (3-4)


COPADM1:

70% (3-4)

COPADM2:

>50% (3-4)


CYVE1 and 2:

10-30% (3-4)


M1:

30% (3-4)

Patte C

Blood 200723

*HD: High Dose
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