MZL

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).