Factors associated with treatments and protocols
Not all cytotoxic drugs have the same toxicity on the oral
mucosa. Table 1 summarizes the various treatments associated with
an increased risk of oral mucositis. The dose administered and
combination of concomitant drugs will also increase the risk of
mucositis.
Table 1: Treatments associated with an increased
risk of oral mucositis5
|
Treatments inducing mucositis
|
|
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
|
The treatments are presented in alphabetical order, and
not in order of their relative mucotoxic potential.
Some protocols using high doses of chemotherapy or
polychemotherapy have been associated with a high incidence of
mucositis:
- Conditioning for an HSC autograft
- Conditioning for an HSC allograft
- Induction phase of the protocol for the treatment of leukemias
and lymphomas
- In pediatrics43
Table 243
|
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 HSC grafts and also the polychemotherapy
for some hematological malignancies and show the incidence of
oral mucositis in these patients.
Table 3: Mucotoxic 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