Treatment Regimens

About Oral Mucositis

Help your patients keep Oral Mucositis away with Caphosol

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