Table 1.

Chemotherapeutic options: polychemotherapy and monotherapeutic options.

	Number of patients	Intent of chemotherapy	Agents used	Response	Time to progression	Survival
McAfee et al. [14] prospective	n = 34  9 patients received CTx local to metastatic disease	Adjuvant	Carboplatin, cisplatin, VP-16, etoposide	NDA	5-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	n = 41  local or locoregional disease	Adjuvant (72%); therapeutic (28%)	CTx combined with RTx; etoposide, carboplatin	NDA	NDA	3-year OS 76%; 3-year DFS 65%
George et al. [16] retrospective	n = 1  metastatic disease	Adjuvant	Cyclophosphamide, doxorubicin, vincristin	CR: 4-5 months	4 months	NDA
Redmond III et al. [17] retrospective	n = 6  metastatic disease	Adjuvant	Cisplatin + etoposide or Cisplatin + etoposide + cyclophosphamide or Cyclophosphamide + doxorubicin + vincristin	CR in 5 patients	CR for a median of 3,5 months	median OS of 6,5 months
Azagury et al. [18] retrospective	n = 1  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	n = 30  NET (1 MCC among all cases) locally advanced or metastatic disease	Adjuvant	5-Fluorouracil + dacarbazine + epirubicin	CR 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	n = 88; 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 months	NDA
Eng et al. [21] retrospective	n = 46  9 patients received CTx metastatic disease	Adjuvant	+/− RTx most common regimen: carboplatin + etoposide + vinblastin	NDA	Overall median time to recurrence was 9 months	OS rate of all cases: 37%
Veness et al. [22] retrospective	n = 86  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 months	5-year OS 47%; DFS rate 25%
Voog et al. [23] retrospective	n = 107  advanced or metastatic disease	Adjuvant	different regimens; NDA	ORR to first line CTx: 64%	NDA	3-year OS was 17% (metastasis) and 35% (locally advanced)
Allen et al. [24] retrospective	n = 251  28 patients received CTx local or regional disease	Adjuvant	most common regimen: carboplatin + etoposide	NDA; 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	n = 5  metastatic disease	Adjuvant	+RTx liposomal doxorubicin	PR in 4 patients	an average of 2 months until progression	Survival time: range 3 to 20 months
Schlaak et al. [26] retrospective	n = 4  metastatic disease	Adjuvant	Etoposide	CR in 3 patients	2 of CR lasted for 16 and 36 months	NDA
Tai et al. [27] retrospective	n = 204  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 months	Median 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.