Review Article

Merkel Cell Carcinoma: Chemotherapy and Emerging New Therapeutic Options

Table 1

Chemotherapeutic options: polychemotherapy and monotherapeutic options.

Number of patientsIntent of chemotherapyAgents usedResponseTime to progressionSurvival

McAfee et al. [14]
prospective

9 patients received CTx
local to metastatic disease
Adjuvant Carboplatin, cisplatin, VP-16, etoposideNDA5-year local control of all cases: 94%;
5-year locoregional control of all cases: 80%
5-year survival of all cases: 37%;
5-year DSS of all cases: 52%

Poulsen et al. [15]
prospective

local or locoregional disease
Adjuvant (72%);
therapeutic (28%)
CTx combined with RTx; etoposide, carboplatinNDANDA3-year OS 76%;
3-year DFS 65%

George et al. [16]
retrospective

metastatic disease
Adjuvant Cyclophosphamide, doxorubicin, vincristinCR: 4-5 months4 monthsNDA

Redmond III et al. [17]
retrospective

metastatic disease
Adjuvant Cisplatin + etoposide
or
Cisplatin + etoposide + cyclophosphamide
or
Cyclophosphamide + doxorubicin + vincristin
CR in 5 patientsCR for a median of 3,5 monthsmedian OS of 6,5 months

Azagury et al. [18]
retrospective

metastatic disease
Adjuvant First line:
VP-16 + cisplatin + doxorubicin + bleomycin

Second line: RTx combined with methotrexate + cyclophosphamide + VP-16
CR after 6 cycles

CR after 4 months
15 months until relapse

NDA
NDA

Bajetta et al. [19]
prospective

NET (1 MCC among all cases)
locally advanced or metastatic disease
Adjuvant 5-Fluorouracil + dacarbazine + epirubicinCR in 2 patients (in 1 patient with MCC);
PR in 7 patients
CR of MCC for 21+ months;
median duration of response of all cases was 10 months (range, 5+ to 24+)
NDA

Eng et al. [20]
retrospective
;
43 patients received RT and/or combined CTx
local to metastatic disease
Adjuvant 19% received CTx without RTx
most common regimen:
VP-16 + cisplatinum
NDA;
of all cases 12% had persistent disease, 40% had recurrent disease
Of all cases median time to recurrence was 8 monthsNDA

Eng et al. [21]
retrospective

9 patients received CTx
metastatic disease
Adjuvant +/− RTx
most common regimen:
carboplatin + etoposide + vinblastin
NDAOverall median time to recurrence was 9 monthsOS rate of all cases: 37%

Veness et al. [22]
retrospective

7 patients received CTx
locoregional disease
Adjuvant most common:
based on platinum
NDA;
55% of all cases experienced a relapse
median time to relapse was 3–7 months5-year OS 47%;
DFS rate 25%

Voog et al. [23]
retrospective

advanced or metastatic disease
Adjuvant different regimens; NDAORR to first line CTx: 64%NDA3-year OS was 17% (metastasis) and 35% (locally advanced)

Allen et al. [24]
retrospective

28 patients received CTx
local or regional disease
Adjuvant most common regimen: carboplatin + etoposideNDA;
disease recurred in 102 patients
of all cases median time to recurrence was 9 months (range, 2 to 70 months)5-year DFS of all cases: 48%;
5-year DSS of patients receiving CTx: 28%

Wobser et al. [25]
retrospective

metastatic disease
Adjuvant +RTx
liposomal doxorubicin
PR in 4 patientsan average of 2 months until progressionSurvival time: range 3 to 20 months

Schlaak et al. [26]
retrospective

metastatic disease
Adjuvant EtoposideCR in 3 patients2 of CR lasted for 16 and 36 monthsNDA

Tai et al. [27]
retrospective

locoregional and metastatic disease
Adjuvant most common regimens:
Cyclophosphamide + doxorubicin (or epirubicin) + vincristin
+/− prednisone

Etoposide + cisplatin (or carboplatin)
ORR 75,7%
(35,1% CR, 35,1% PR, 5,4% minor responses)

ORR 60%
(36% CR, 24% PR)
Median response duration of patients receiving CTx: 1–12 monthsMedian OS of all cases: 21,5 months (range, 1 to 118 months);
2-year OS of all cases: 36%;
5-year OS of all cases: 17%

NDA: no data available; NET: neuroendocrine tumor(s); MCC: merkel cell carcinoma; PR: partial response; CR: complete response; CTx: chemotherapy; RTx: radiation therapy; Sx: surgery; DFS: disease free survival; OS: overall survival; ORR: overall response rate; DSS: disease-specific survival.