Table 1.

Studies of Oral Cryotherapy in Solid Malignancies

Reference	Year	Randomized	No. in Intervention/Control Group	Type of Cryotherapy	Duration of Cryotherapy	Chemo Regimen	Mucositis Staging	Intervention Group	Control Group
Mahood13	1991	Yes	50/45	Ice chips	5 min pre-5FU and then for 30 min	5FU/LV	Mean patient and physician judged mucositis grading (0- 4), mean score	Patient: 1.1 Physician: 0.9	2.4 1.9
Rocke30	1993	Yes	89/89a	Ice chips	5 min pre-5FU and then for 30 or 60 min	5FU/LV	Mean patient and physician judged mucositis grading (0- 4), mean score	Patient: 30 min: 0.73 60 min: 1 Physician: 30 min: 0.58 60 min: 0.79
Cascinu14	1994	Yes	44/40	Ice chips	5 min pre-5FU and then for 30 min	5FU/LV +/− etoposide or interferon	Combined patient and physician judged mucositis grading (0-4), mean score	0.59	1.1
Dreicer25	1997	No	37/−	Ice chips	30 min prior to edetrexate infusion	Edatrexate	ECOG grade, Grade 3-4	38%
Gandara26	1997	No	23/−	Ice chips	5 min pre, during, and 15 min after edetrexate infusion	Edatrexate + carboplatin	Not specified, Grade 3	13%
Edelman22	1998	No	46/−	Ice chips	5 min pre, during, and 15 min after edetrexate infusion	Edatrexate + carboplatin	CTC, Grade 1-4	Grade 1-2: 59% Grade 3-4: 15%
Hudes109	1999	No	27/−	Ice chips	5 min pre-5FU and then for 30 min	5FU/LV + Interferon	CTC, Grade 3-4	36%
Yokomizo29	2004	No	20/32	Allopurinol ice balls	Prior to 5FU infusion and at 2, 4, and 6 hours until melted	5FU/LV	CTC, Grade 1-4	Grade 1-2: 15% Grade 3-4: 0%	41% 6%
Karagozoglu20	2005	Yes	30/30	Smooth ice cubes	5 min pre-chemo until all infusions complete	Etoposide, cisplatin, mitomycin, vinblastine	Patient and physician judged mucositis grading (0-4), Grade 1-4	Patient: 37% Physician: 10%	90% 50%
Nikoletti31	2005	Yes	67/67/67b	Plain ice or flavored ice	5 min pre and during, until 20 min after 5FU	5FU +/− LV	Oral Assessment Guide, ORc	None vs. Plain: 3.26 None vs. flavored: 3.5 Plain vs. flavored: 1.07
Baydar110	2005	Yes	45/54d	Ice chips	Start of infusion until 10 min after 5FU	5FU/LV	WHO, Grade 1-3	7% (only Grade 1)	39% (Grade 1-3)
Papadeas32	2007	Yes	36/40	Crushed ice	5 min pre and during, until 30 min after 5FU	5FU/LV	Patient and physician judged mucositis grading (0-4); Grade 3	Patient: 17% Physician: 11%	23% 13%
Sorensen21	2008	Yes	70/64/63e	Crushed ice	10 min pre-5FU and then for 35 min	5FU/LV	CTC, Grade 3	Cryotherapy: 10% Chlorhexidine: 11%	32%
Katranci111	2011	Yes	30/30	Crushed ice	5 min pre, during, and up to 15 min after 5FU	5FU/LV	WHO, Grade 3	3%	20%

5FU = 5- fluorouracil; LV = leucovorin; WHO =World Health Organization; CTC = Common Toxicity Criteria; OR = odds ratio; ECOG = Eastern Cooperative Oncology Group.

^aPatients were randomized to either 30 or 60 minutes of oral cryotherapy.

^bAll 67 patients were randomized sequentially in a crossover design during three cycles of therapy to flavored ice, plain ice, and no ice.

^cReported by authors only as OR as odds of symptoms increasing vs. not increasing.

^d40 patients in total; patients were randomized to either cryotherapy (n=45) or standard care (n=54) initially and then crossed-over at next cycle.

^eArms A/B/C are chlorhexidine/normal saline/cryotherapy, respectively.