ESMO 2016 | Selected Oral Presentations: EMZL – clarithromycin dose for treating EMZL is 1g/day

Dr Caterina Cecchetti, from the San Raffaele Scientific Institute in Milan, Italy, and colleagues presented during the ESMO congress in October 2016 in Copenhagen, Denmark, a retrospective study on 55 patients with Extranodal Marginal Zone Lymphoma (EMZL) treated by clarithromycin monotherapy.

The study had three treatment schedules: 500mg clarithromycin twice per day for six months (n=13), three courses of 500mg twice per day for 21 days, every 35 days (n=19), and four courses of 2g per day for 14 days, every 21 days (n=23). The primary outcome was the efficacy and safety of the treatment schedules. 

The authors presented data showing that the Overall Response Rate (ORR) of the 1g/day and 2g/day treatment groups were 40% and 46% respectively (P=0.28). Data presented also showed that the Complete Response (CR) rate of the 1g/day and 2g/day treatment groups were 12% and 39%, respectively (P=0.02).

Response	N(%)	1 g/day - 32 pts (%)	2 g/day - 23 pts (%)	P
CR	13 (24)	4 (12)	9 (39)	0.02
PR	13 (24)	9 (28)	4 (17)
ORR	26 (47)	13 (40)	13 (56)	0.28
SD	16 (29)	12 (37)	4 (17)
PD	13 (23)	7 (21)	6 (26)

The reported overall Progression Free Survival (PFS) rate, with median follow-up time of 33 months, was found to be 52 ± 7%. The PFS for each treatment group was 60 ± 9% (1g/day) and 42 ± 10% (2g/day).

There was one significant difference in the toxicity profile: the rate of nausea in the 1g/day and 2g/day groups which had a rate of 25% and 52%, respectively (P=0.03). There were no incidence of any grade 4 side effects in either dosage group.

Clarithro 1 g/day - 32 patients (%)
Side effects	Grade 1	Grade 2	Grade 3	Grade 4	Any Grade
Nausea	5	2	1	0	8 (25)
Disgeusia	4	1	0	0	5
Dizziness	2	2	0	0	4
Headache	1	0	0	0	1
Arthralgia	0	1	0	0	1
Rash	0	1	0	0	1

Clarithro 2 g/day - 23 patients (%)
Side effects	Grade 1	Grade 2	Grade 3	Grade 4	Any Grade
Nausea	7	3	2	0	12 (52)
Disgeusia	2	0	0	0	2
Dizziness	4	0	0	0	4
Headache	2	0	0	0	2
Arthralgia	0	1	0	0	1
Rash	1	0	0	0	1

The main conclusion from this presentation was that in future the recommended dose should be 1g/day to balance efficacy and tolerability. At the end of the presentation a new trial of clarithromycin was discussed. The CLEO trial is a phase II trial using 1g/day clarithromycin in combination with lenalidomide in patients with R/R EMZL.

Following Dr Caterina Cecchetti’s presentation, a discussion session was held, led by Dr Armando López-Guillermo from Instituto Oncológico Baselga, Barcelona, Spain. Dr López-Guillermo commented on the anti-tumor mechanisms of action of clarithromycin which included increasing the activity of macrophages and reducing neutrophil production of Vascular Endothelial Growth Factor (VEGF).