1. health and fitness
2. disease
3. cancer

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Oral Mucositis:
Causative Regimens and
Pathways for Treatment
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From the publisher of
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Oral Mucositis:
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Causative Regimens and
Pathways for Treatment
James D’Olimpio, MD, FACP
Director
Supportive Oncology, Pain and Symptom
Management Program
Monter Cancer Center of North Shore
University Hospital
Lake Success, New York
Assistant Professor of Medicine
New York University School of Medicine
New York, New York
Val R. Adams, PharmD, FCCP, BCOP
Avoid eating or drinking at least 15 minutes after
use. Patients restricted to a low sodium diet should
consult their physician before use. Federal law
restricts this device to sale by or on the order of a
physician or dentist. Keep out of reach of children.
Associate Professor
University of Kentucky,
College of Pharmacy
Lexington, Kentucky
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Table of Contents
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Structure and Function of Oral Mucosa
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Incidence of Oral Mucositis
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Figure 1. The oral mucosa.
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Introduction
Table 1. Oral Mucositis Associated With
Selected Regimens for Common Tumors
8-15
Table 2. Oral Mucositis Associated
With Selected Chemoradiation Regimens
16-19
Pathobiology of Oral Mucositis
Disclaimer
20-21
Figure 2. Pathobiology of mucositis.
22-23
Treatment Guidelines
23-26
Table 4. Oral Mucositis Assessment Scales
24-25
Table 5. Tenets of Oral Mucositis Care
25
Conclusion
26
References
26-29
d.
PG08114
Table 3. Oral Mucosal Toxicity Associated
With Selected Hematopoietic Stem Cell
Transplant Preparative Regimens
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This pocket guide is designed to be a summary of information. While it
is detailed, it is not an exhaustive clinical review. McMahon Publishing,
EUSA Pharma and the authors neither affirm or deny the accuracy of
information contained herein. No liability will be assumed for the use of this
pocket guide, and the absence of typographical errors is not guaranteed.
Readers are strongly urged to consult any relevant primary literature, the
complete prescribing information available in the package insert of each
drug and appropriate clinical protocols. Copyright © 2008, McMahon
Publishing, 545 West 45th Street, New York, NY 10036. Printed in the USA.
All rights reserved, including the right of reproduction, in whole or in part,
in any form.
18-22
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Introduction
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ucositis can be best described as a distinct and complex
pathobiologic entity resulting in mucosal barrier injuries
that is a consequence and frequent complication of chemotherapy (CT) and radiation therapy (RT) in patients with cancer.1
These injuries can be limited to the oral mucosa (stomatitis or
oral mucositis [OM]), or can involve the entire gastrointestinal
tract/orodigestive tract (gastrointestinal mucositis/alimentary
mucositis [GM/AM]).2,3 Regardless of the taxonomy used, given
the similarities in embryologic origins and requisite histologic
and evolutionary differences in structure and function, OM,
which has been most studied, serves as the model when assessment and treatment considerations are planned and discussed.3
OM can be considered the primary entity for the purposes of understanding the multitude of clinical issues involved in improving
overall patient management and refining practice guidelines.
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Macrophages
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Structure and Function of Oral Mucosa
The oral mucous membrane is a complex array of cellular and
extracellular components, including squamous, stratified keratinized epithelium, in the gums and hard palate, and nonkeratinized epithelia proximal and distal to these areas, in the soft
palate (Figure 1).4,5 A thin lamina propria rests underneath.
Stem cells for these structures, as well as immune-competent
reticulo-endothelial lymphoid tissue and highly developed nociceptors, continuously sense pain and discomfort.6 Additionally,
there are salivary glands that can produce saliva of different
viscosities (eg, thicker in consistency in the submental region).
Saliva is a highly complex and dynamic liquid containing multiple signaling elements, such as calcium ions, cytokines, growth
factors, peptides, and proteases, all of which are dynamically
balanced to maintain physiologic and anatomic integrity.6,7
Incidence of Oral Mucositis
Fibroblasts
Extracellular
matrix
Figure 1. The oral mucosa.
Based on reference 4.
the case of systemic chemotherapeutic agents, used alone or
in combination, rates of OM are highly variable. Because OM
is underreported, accurate data are not consistently available
from report to report, and, hence, data for solid tumor treatment programs are not concordant with those for leukemia and
lymphoma. CT alone generally is associated with the lowest
incidence of mucositis (22%), whereas the rates in patients
treated with conventional RT and chemoradiation are much
higher (97% and 89%, respectively).8 Certain drugs (eg, methotrexate, 5-fluorouracil, etoposide, irinotecan, cytarabine,
cyclophosphamide, platinum agents, and anthracyclines) and
combinations of these drugs (such as preparative regimens for
stem cell transplant, induction regimens for leukemia and lymphoma, and head and neck cancer regimens) have been shown
to be more frequently associated with OM (Tables 1-3).9-39 OM
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This delicate balance is upset by anticancer therapy, and
the extent of the disruption depends on the therapies used. In
Capillaries
8
9
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Table 1. Oral Mucositis Associated With Selected
Regimens for Common Tumors (continued)
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Incidence of Oral
Mucositis (All Grades)a
Reference (Ref. no.)
53%
Martin, et al. N Engl J Med.
2005;352(22);2202-2213 (9)
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Fluorouracil 500 mg/m2 I.V., day 1
Doxorubicin 50 mg/m2 I.V., day 1
Cyclophosphamide 500 mg/m2 I.V., day 1
Repeat every 21 days
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Breast Cancer
FAC
(N=736)
Co
gh
Regimen
(Number of Patients)
69%
Martin, et al. N Engl J Med.
2005;352(22);2202-2213 (9)
DCH
(N=70)
Docetaxel 75 mg/m2 I.V., day 1
Carboplatin dosed to an AUC 6b I.V., day 1
Repeat every 21 days
Trastuzumab 4 mg/kg I.V. load, then
weekly 2 mg/kg I.V.
25%c
Coudert et al. J Clin Oncol.
2007;25(19):2678-2684 (10)
AC
(N=510)
Doxorubicin 60 mg/m2 I.V., day 1
Cyclophosphamide 600 mg/m2 I.V., day 1
Repeat every 21 days
45%
Jones et al. J Clin Oncol.
2006;24(34):5381-5387 (11)
TC
(N=506)
Docetaxel 75 mg/m2 I.V., day 1
Cyclophosphamide 600 mg/m2 I.V., day 1
Repeat every 21 days
33%
Jones et al. J Clin Oncol.
2006;24(34):5381-5387 (11)
AT
(N=213)
Doxorubicin 50 mg/m2 I.V., day 1
Docetaxel 75 mg/m2 I.V., day 1
Repeat every 21 days
58%
Nabholtz et al. J Clin Oncol.
2003;21(6):968-975 (12)
Capecitabine-lapatinib
(N=152)
Capecitabine 1,000 mg/m2 PO twice
daily, days 1-14
Lapatinib 1,250 mg PO daily
Repeat every 21 days
15%
Geyer et al. N Engl J Med.
2006;355(26):2733-2743 (13)
Capecitabine
(N=152)
Capecitabine 1,250 mg/m2 PO twice
daily, days 1-14
Repeat every 21 days
12%
Geyer et al. N Engl J Med.
2006;355(26):2733-2743 (13)
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Docetaxel 75 mg/m2 I.V., day 1
Doxorubicin 50 mg/m2 I.V., day 1
Cyclophosphamide 500 mg/m2 I.V., day 1
Repeat every 21 days for 6 cycles
ro
TAC
(N=744)
AUC, area under the curve; I.V., intravenous; NHL, non-Hodgkin’s lymphoma;
NSCLC, non-small cell lung cancer; PO, orally
a
b
All grades unless otherwise noted.
Calculated using the Calvert formula.
Includes gastrointestinal/alimentary mucositis.
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Table 1. Oral Mucositis Associated With Selected
Regimens for Common Tumors (continued)
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Regimen
(Number of Patients)
Reference (Ref. no.)
16%
Jones et al. J Clin Oncol.
2005;23(24):5542-5551 (14)
51%
Jones et al. J Clin Oncol.
2005;23(24):5542-5551 (14)
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Incidence of Oral
Mucositis (All Grades)a
Breast Cancer (continued)
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Docetaxel
(N=222)
Docetaxel 100 mg/m2 I.V., day 1
Repeat every 21 days
Capecitabine-docetaxel
(N=251)
Capecitabine 1,250 mg/m2 PO twice
daily, days 1-14
Docetaxel 75 mg/m2 I.V., day 1
Repeat every 21 days
17% grades III and IV
O’Shaughnessy et al. J Clin Oncol.
2002;20(12):2812-2823 (15)
Liposomal doxorubicin
(N=150)
Liposomal doxorubicin 50 mg/m2 I.V.,
day 1
Repeat every 28 days
22%
Keller et al. J Clin Oncol.
2004;22(19):3893-3901 (16)
XELOX
(N=171)
Capecitabine 1,000 mg/m2 PO twice
daily, days 1-14
Oxaliplatin 130 mg/m2 I.V., day 1
Repeat every 21 days
30%
Diaz-Rubio et al. J Clin Oncol.
2007;25(27):4224-4230 (17)
FOLFOX4
(N=1,108)
Leucovorin 200 mg/m2 I.V. over 2 hours,
days 1 and 2
Fluorouracil 400 mg/m2 I.V. bolus, days
1 and 2
Fluorouracil 600 mg/m2 I.V. continuous
infusion over 22 hours, days 1 and 2
Oxaliplatin 85 mg/m2 I.V., day 1 (given
at the same time as leucovorin)
Repeat every 14 days
42%c
Andre et al. N Engl J Med.
2004;350(23):2343-2351 (18)
FOLFIRI
(N=110)
Irinotecan 180 mg/m2 I.V. over 1.5
hours, day 1
Leucovorin 200 mg/m2 I.V. over 2 hours,
day 1
Fluorouracil 400 mg/m2 I.V. bolus, day 1
Fluorouracil 2,400-3,000 mg/m2 I.V.
continuous infusion over 46 hours, day 1
Repeat every 14 days
51%c
Tournigand et al. J Clin Oncol.
2004;22(2):229-237 (19)
©
Paclitaxel 175 mg/m2 I.V., day 1
Repeat every 21 days
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Paclitaxel
(N=222)
Colorectal Cancer
a
d.
All grades unless otherwise noted.
Calculated using the Calvert formula.
c
Includes gastrointestinal/alimentary mucositis.
b
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AUC, area under the curve; I.V., intravenous; NHL, non-Hodgkin’s lymphoma;
NSCLC, non-small cell lung cancer; PO, orally
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Table 1. Oral Mucositis Associated With Selected
Regimens for Common Tumors (continued)
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Co
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Regimen
(Number of Patients)
Reference (Ref. no.)
46%c
Tournigand et al. J Clin Oncol.
2004;22(2):229-237 (19)
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Incidence of Oral
Mucositis (All Grades)a
t
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Colorectal Cancer (continued)
FOLFOX6
Oxaliplatin 100 mg/m2 I.V. over 2 hours,
days 1 and 2
(N=110)
Leucovorin 200 mg/m2 I.V. over 2 hours,
day 1
Fluorouracil 400 mg/m2 I.V. bolus, day 1
Fluorouracil 2,400-3,000 mg/m2 I.V.,
continuous infusion over 46 hours, day 1
Repeat every 14 days
©
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Prostate Cancer
Docetaxel 75 mg/m2 I.V., day 1
Prednisone 5 mg daily
Repeat every 21 days
20%
Taxotere P.I. Sanofi-aventis (20)
MVAC
(N=129)
Methotrexate 30 mg/m2 I.V.,
days 1, 15, and 22
Vinblastine 3 mg/m2 I.V.,
days 2, 15, and 22
Doxorubicin 30 mg/m2 I.V., day 2
Cisplatin 70 mg/m2 I.V., day 2
Repeat every 28 days
70%c
Sternberg et al. J Clin Oncol.
2001;19(10):2638-2646 (21)
GC
(N=182)
Gemcitabine 1,000 mg/m2 over
30-60 minutes I.V., days 1, 8, and 15
Cisplatin 70 mg/m2 I.V., day 2
Repeat every 28 days
1% grades III and IV
von der Maase et al. J Clin Oncol.
2000;17(17):3068-3077 (22)
Carboplatin-paclitaxel
(N=533)
Paclitaxel 175 mg/m2 I.V. over 3 hours,
day 1
Carboplatin AUC 5b I.V., day 1
Repeat every 21 days
6%
Vasey et al. J Natl Cancer Inst.
2004;96(22):1682–1691 (23)
Carboplatin-docetaxel
(N=539)
Docetaxel 75 mg/m2 I.V. over 1 hour,
day 1
Carboplatin AUC 5b I.V., day 1
Repeat every 21 days
9%
Vasey et al. J Natl Cancer Inst.
2004;96(22):1682–1691 (23)
Docetaxel-prednisone
(N=332)
Bladder Cancer
Ovarian Cancer
a
d.
All grades unless otherwise noted.
Calculated using the Calvert formula.
c
Includes gastrointestinal/alimentary mucositis.
b
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AUC, area under the curve; I.V., intravenous; NHL, non-Hodgkin’s lymphoma;
NSCLC, non-small cell lung cancer; PO, orally
14
15
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Table 1. Oral Mucositis Associated With Selected
Regimens for Common Tumors (continued)
ri
Schedule
py
ts
Co
gh
re
Incidence of Oral
Mucositis (All Grades)a
Reference (Ref. no.)
24%
Johnson et al. J Clin Oncol.
2004;22(11):2184-2191 (24)
gh
se
NSCLC
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Regimen
(Number of Patients)
t
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Cisplatin-vinorelbine
(N=396)
Cisplatin 100 mg/m2 I.V., day 1
Vinorelbine 25 mg/m2 I.V., days 1, 8, 15,
and 22
Repeat every 28 days
21%
Taxotere P.I. Sanofi-aventis (20)
Cisplatin-docetaxel
(N=406)
Cisplatin 75 mg/m2 I.V., day 1
Docetaxel 75 mg/m2 I.V., day 1
Repeat every 21 days
24%
Taxotere P.I. Sanofi-aventis (20)
Cisplatin-gemcitabine
(N=67)
Cisplatin 100 mg/m2 I.V., day 1
Gemcitabine 1,250 mg/m2 I.V., days 1
and 8
Repeat every 21 days
20%
Gemzar P.I. Lilly (25)
Carboplatin-gemcitabine
(N=197)
Gemcitabine 1,200 mg/m2 I.V., days 1
and 8
Carboplatin AUC 5b I.V., day 1
Repeat every 21 days
29%
Rudd et al. J Clin Oncol.
2005;23(1):142-153 (26)
27%
Coiffier et al. N Engl J Med.
2002;346(4):235-242 (27)
©
Paclitaxel 200 mg/m2 I.V. over 3 hours,
day 1
Carboplatin AUC 6b I.V., day 1
Bevacizumab 15 mg/kg I.V., day 1
Repeat every 21 days
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Non-Hodgkin’s Lymphoma
R-CHOP
(N-202)
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Carboplatin-paclitaxelbevacizumab
(N=35)
Cyclophosphamide 750 mg/m2 I.V., day 1
Doxorubicin 50 mg/m2 I.V., day 1
Vincristine 1.4 mg/m2 I.V., day 1
(max. 2-mg dose)
Prednisone 40 mg/m2 PO, days 1-5
Rituximab 375 mg/m2, day 1
Repeat every 21 days
a
b
c
d.
All grades unless otherwise noted.
Calculated using the Calvert formula.
Includes gastrointestinal/alimentary mucositis.
te
AUC, area under the curve; I.V., intravenous; NHL, non-Hodgkin’s lymphoma;
NSCLC, non-small cell lung cancer; PO, orally
16
17
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Table 2. Oral Mucositis Associated
With Selected Chemoradiation Regimens
ri
Co
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Incidence of Oral
Reference (Ref. no.)
Mucositis (Grades III and IV)a
py
ts
Regimen
Dosing
(Number of Patients)
ri
se
gh
re
Head and Neck Cancer
t
rv
Cisplatin-radiation
(N=171)
Cisplatin 100 mg/m2 I.V., days 1, 22,
and 43 of radiotherapy
Radiation 70 Gy in 35 fractions of
2 Gy/day over 7 weeks
Cetuximab-radiation
(N=208)
Carboplatin-radiation
(N=386)
Cetuximab 400 mg/m2 I.V. x 1, then
250 mg/m2 I.V. every week
1 week after cetuximab, begin fractionated
radiation 70-76.8 Gyb
56%c
Bonner et al. N Engl J Med.
2006;354(6):567-578 (29)
Carboplatin AUC 1.5d I.V. weekly to a
max. of 7 weeks
Radiation 70-74 Gy in fractions of
2 Gy/day, 5 days/weeke
37%-38% depending on
induction chemotherapy
regimen
Posner et al. N Engl J Med.
2007;357(17):1705-1715 (30)
Cisplatin-etoposideradiation
(N=50)
Cisplatin 50 mg/m2 I.V., days 1, 8, 29,
and 36
Etoposide 50 mg/m2 I.V., days 1-5
and 29-33
Radiation 45-61 Gy in 1.8 Gy/day
fractions, 5 days/week
20%c
Albain et al. J Clin Oncol.
2002;20(16):3454-3460 (31)
Carboplatin-paclitaxelradiation
(N=92)
Carboplatin AUC 2d I.V., day 1
Paclitaxel 45 mg/m2 I.V., day 1
Radiation 63 Gy in 34 fractions
Repeat weekly for 7 weeks
Pacitaxel 200 mg/m2
Carboplatin AUC 6
2 cycles every 21 days
28%f
Belani et al. J Clin Oncol.
2005;23(25):5883-5891 (32)
©
Forastiere et al. N Engl J Med.
2003;349(22):2091-2098 (28)
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43%
NSCLC, Stage III
d
e
f
Calculated using the Calvert formula.
See Posner et al 2007 for induction chemotherapy regimen.
Esophagitis.
te
AUC, area under the curve; Gy, gray; I.V., intravenous
a
Grades III and IV unless otherwise noted.
b
See Bonner et al 2006 for detailed radiation dosing.
c
Includes gastrointestinal/alimentary mucositis.
d.
18
19
A
Table 2. Oral Mucositis Associated
With Selected Chemoradiation Regimens
ll
ri
Co
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ri
gh
se
Paclitaxel 200 mg/m2 I.V., days 1 and 22
Carboplatin AUC 6d I.V., days 1 and 22
Fluorouracil 225 mg/m2 per day
continuous I.V. infusion, days 1-42
Radiation 45 Gy in 1.8 Gy/day fractions
5 days/week
t
rv
Meluch et al. Cancer J.
2003;9(4):251-260 (33)
20
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Cisplatin-5-FU-radiation Cisplatin 100 mg/m2 I.V., days 1 and 29
Fluorouracil 1,000 mg/m2/day continuous
(N=29)
infusion on days 1-4 and 29-32
Radiation 50.4, 45 Gy in 1.8 Gy fractions
with a final 5.4 Gy boost
AUC, area under the curve; Gy, gray; I.V., intravenous
a
Grades III and IV unless otherwise noted.
b
See Bonner et al 2006 for detailed radiation dosing.
c
Includes gastrointestinal/alimentary mucositis.
rates with radiation treatment are high, whether in combination with chemotherapy or even in programs designed to limit
the field of exposure.
Pathobiology of OM
43%c
©
ed
Carboplatin-5-FUpaclitaxel-radiation
(N=129)
re
Esophageal Cancer
Incidence of Oral
Reference (Ref. no.)
Mucositis (Grades III and IV)a
py
ts
Regimen
Dosing
(Number of Patients)
d
e
f
Tepper et al. J Clin Oncol.
2008;26(7):1086-1092 (34)
Calculated using the Calvert formula.
See Posner et al 2007 for induction chemotherapy regimen.
Esophagitis.
Nutritional deficits develop rapidly, and poor treatment outcomes ensue, commonly from incomplete compliance with
planned schedules or attenuated dosing formats.
Accumulating evidence has validated the theoretic constructs of these events; their sequence, originally felt to be
linear and limited to the epithelial layers, has been expanded
to include both preclinical and clinical changes expressed
in relatively discrete but overlapping phases. These phases,
originally described and further advanced by Sonis and others,1,2 include the following:
1. Initiation: The direct reversible and irreversible damage
to DNA and activation of pathways not requiring oxygenspecies activation that occur at the start of a given therapy
and are subclinical.
2. Upregulation and message generation: The activation of
te
d.
OM results in an inflammatory cascade of complex interactive processes that lead to painful breakdowns in the
natural barrier state. Erythema, ulcerations, bleeding, and
breakdown of cellular and matriceal structures follow, with
a loss of the ability to prevent pathogenic bacteria from invading the mouth and, ultimately, the bloodstream in more
profoundly immunosuppressed patients. Toxic effects include painful membranes with ulceration, inadequate nutrition from poor intake and absorption of nutrients, psychosocial distress, and potentially life-threatening infection.1,40
42%f
20
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Table 3. Mucosal Toxicity Associated With Selected
Hematopoietic Stem Cell Transplant Preparative
Regimens
ri
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Schedule
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Regimen
(Number of Patients)
Incidence of Mucosal
Toxicity
Reference (Ref. no.)
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96% Bearman grades I and II
Kroger et al. Bone Marrow Transplant. 2001;27(4):349-354 (35)
Bu-Cy
(N=69)
Busulfan 1 mg/kg 4 times daily PO, days
–7, –6, –5, and –4
Cyclophosphamide 60 mg/kg I.V., days
–3 and –2
90% Bearman grades I and IIa
Rosenthal et al. Leuk Lymphoma.
1994;14(3-4):279-283 (36)
Melphalan
(N=47)
Melphalan 200 mg/m2 I.V.
67% grades II-IV
Spencer et al. Bone Marrow
Transplant. 2005;35(10):971-977
(37)
Radiation-cyclophosphamide-etoposidecarboplatin
(N=35)
Radiation 2 Gy twice daily, days –8, –7,
and –6
Cyclophosphamide 2,000 mg/m2/d I.V.,
days –5, –4, and –3
Etoposide 600 mg/m2/d I.V., days –5, –4,
and –3
Carboplatin 333 mg/m2 per day
continuous infusion days –5, –4, and –3
94% grades III and IV
Gabriel et al. Biol Blood
Marrow Transplant. 2005;11:
1022-1030 (38)
Bu-Cy-VP
(N=31)
Busulfan 4 mg/kg, days –8, –7, –6, and –5
Etoposide 60 mg/kg I.V., day –4
Cyclophosphamide 60 mg/kg, days –3
and –2
100% Bearman grades II-IV
Zander et al. Clin Cancer Res.
1997;3:2671-2675 (39)
©
Radiation 1,200 cGy given over 3 days in
6 fractions
Cyclophosphamide 60 mg/kg I.V., days
–4, and –3
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TBI-Cy
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Gy, gray; I.V., intravenous; PO, orally
a
Oral mucositis.
ceramide pathway, which further destabilizes the mucosal
microenvironment.
4. Ulceration: The loss of mucosal cellular and extracellular
integrity leads to ulceration and then bacterial colonization and further cytokine showering.
5. Healing: The spontaneous communication between mesenchyme and epithelial layers leads to healing that may be
complete or incomplete, depending on multiple preexisting factors in the cascade.
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nuclear factor kappa B (NF-κB) and other inflammatory
pathways and transcription of gene products in endothelium, macrophages, and fibroblasts that increase proinflammatory cytokines and metalloproteases, among other effector proteins. This then causes apoptosis and tissue injury
in a cycle of reinvigoration and escalation of substrates
involved, leading to phase 3.
3. Signal amplification: Apoptosis and tissue injury mediates
and perpetuates additional feedback amplification and the
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23
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Figure 2. Pathobiology of mucositis.
Based on reference 1.
Treatment Guidelines
Despite these dramatic improvements in the knowledge
base, and the paradigm shifts that have taken place in recent
years, the importance of diagnosis and treatment of OM has
been underappreciated, and it has been undertreated for a variety of reasons. Grading and assessment schemas (either the
National Cancer Institute or World Health Organization formats
are most common; Table 4)41-43 are still idiosyncratic and inconsistently applied from center to center, and unifying consensus-based guidelines are not fully adopted. Those that are evidence-based (eg, Multinational Association for Supportive Care
te
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Figure 2 graphically depicts these stages.1 The clinical
manifestations lag behind the first sequence of events, typically by 5 to 10 days for CT (shorter in GM/AM) and 2 weeks
for RT, until patients demonstrate toxicities that last 2 weeks
for CT and 6 to 8 weeks for RT.
The therapeutic strategies that target these phases to prevent downstream accumulation of toxicity and either eliminate
or attenuate the clinical manifestations are the cornerstone
of diagnosis and therapy of OM and, when differences in cell
turnover and structural differences are taken into account, of
GM/AM as well.1,2,40
Reproduced with permission:J Support Oncol 2004;2(suppl 3):003–008 © 2004
Elsevier Inc. All rights reserved.Oral Mucositis in Cancer Therapy, Stephen T.
Sonis, DMD, DMSc.
24
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Table 4. Oral Mucositis Assessment Scales
ri
Grade II
Grade III
Grade IV
Grade V
WHO
criteria
No
changes
Erythema, ulcers, can
eat solids
Ulcers, liquid diet only
Alimentation not
possible
NA
NCI CTC
v3.0
criteria
NA
Erythema of the
mucosa
Patchy ulcerations or
pseudomembranes
Confluent ulcerations or
pseudomembranes;
bleeding with minor
trauma
Tissue necrosis;
Death
significant spontaneous
bleeding; life-threatening
consequences
Bearman
criteria
NA
Pain and/or ulceration not requiring a continuous
I.V. narcotic drug
Co
Grade 0 Grade I
gh
Source
py
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Soreness with
erythema
ri
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Severe ulceration and/
Death
or mucositis requiring
preventive intubation; or
resulting in documented
aspiration pneumonia with
or without intubation
NA
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Pain and/or ulceration
requiring a continuous
I.V. narcotic drug
(morphine drip)
I.V., intravenous; NA, not applicable; NCI CTC, National Cancer Institute Common
Terminology Criteria; WHO, World Health Organization
Adapted from references 41-43.
• Importance of interdisciplinary contribution including nutrition
and oral care specialists
• Use of patient-controlled analgesia and validated tools to assess
effectiveness of controlling pain and suffering
• Include use of benzydamine and exclude use of chlorhexidine
and antimicrobial lozenges as preventatives in RT
• Exclude acyclovir as a preventative in CT and exclude use of
sucralfate and chlorhexidine as primary treatment in patients
undergoing CT/RT
• Use of cryotherapy for 30 minutes prior to bolus 5-fluorouracil
chemotherapy
• Use of palifermin as a preventative in HSCT over a 3-day period
• Use of Caphosol® as an adjunct in the management of OM
associated with high-dose CT and RT/HSCT
• Exclude pentoxifylline or granulocyte-macrophage colonystimulating factor as a preventative in HSCT
• Use of low-level laser therapy as a preventative in centers
where the resource exists
• Proper use of amifostine as a radioprotectant in a dose of
340 mg/m2 given within 30 minutes of RT
te
CT, chemotherapy; HSCT, hematopoietic stem cell transplantation;
RT, radiotherapy
d.
in Cancer/International Society of Oral Oncology) were updated
in 2007/2008, but they reflect a database that is now almost 3
years old.44 Nevertheless, updated guidelines are important and
have “demythologized” many of the previously held tenets of
care and emphasized the continuing role of others (Table 5).
Thus, even if clinical practice is uniformly applied, there is
insufficient evidence to predict that a comprehensive approach
using the guidelines will make a major impact on OM in ways
that take full advantage of the basic pathobiologic construct on
which clinicians agree. The lack of truly stand-alone therapies
in the current guidelines is primarily responsible for this paradox. As it stands, the physical, psychological, and economic
burdens that patients face are significant. Risk factors that can
predict which patient groups may benefit most from emerging
therapies will likely have the most immediate impact. Originally described based on demographic data, such as age (younger
age increases risk), the presence of preexisting periodontal disease/xerostomia, nutritional deficiencies and immunosuppression, it is becoming clear that new bioinformatic techniques
Table 5. Tenets of Oral Mucositis Care
26
27
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evaluating genetic polymorphisms can be much more precise in
assessing risk and treatment stratification.
py
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Conclusion
se
gh
Effective treatments for OM should include combinations
of available agents for both topical and systemic use, and the
careful addition of newer agents such as: 1) glutamine in a more
bioavailable form (not for use in GM/AM)44; 2) additional nonprotein thiols related to amifostine, such as N-acetylcysteine1;
3) Caphosol® (EUSAPharma), a supersaturated solution of calcium and phosphate associated with a significant decrease in
the number days of mucositis, peak level of mucositis and days
requiring morphine45; and 4) targeted nutraceutical therapies.46 Many other therapies are in preclinical development.
This is an exciting time in the field of mucositis, and patients
will likely derive great benefit from these potential improvements in management.
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39.
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41.
42.
43.
44.
45.
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Brought to you by the makers of
For more information, visit www.caphosol.com
or call 1-800-833-3533.
Please see enclosed full prescribing information.
C-0200-08