Table 1.
The studies of Electrochemotherapy in Head and Neck Cancers.
| Author | Year | Type of Trial | N | Pathology: # of Patients | Drug | Rout * | Outcome * | Note | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Panje WR et al. | 1998 | Phase I/II | 10 | SCC: 8 ACC: 1 ADC: 1 |
Bleomycin | I.T | OR: 80%(CR:40%) | Two patients who refused surgery and RT were enrolled. | [73] |
| Hofmann GA et al. | 1999 | Phase I/II | 10 | SCC: 8 ADC: 2 |
Bleomycin | I.T | OR: 80% (SCC: 75%(CR:25%)) (ACC: 100%(CR:50%)) |
[74] | |
| Rabussay DP et al. | 2002 | Phase II | 54 (North American I study: 17) (North American II study: 25) (European study: 12) |
SCC: 54 | Bleomycin | I.T | North American I study: 55% (CR: 30%) North American II study: 58% (CR: 19%) European study: 56% (28%) |
[75] | |
| Burian M et al. | 2003 | Prospective | 12 | SCC: 12 | Bleomycin | I.T | OR: 100% (CR: 83.3%) | 10 patients received ND concurrent with ECT. Seven patients received RT following ECT. |
[76] |
| Bloom DC et al. | 2005 | Phase II | 54 | SCC: 54 | Bleomycin | I.T | Two patients withdrew due to adverse events. Eight other patients were treated with BM alone ECT had significantly higher effectiveness (by more than 50%) than bleomycin and cisplatin alone. |
[47] | |
| Matthiessen LW et al. | 2011 | Phase II | 51 | MM ADC BCC SCC Others |
Bleomycin | I.V: 30 I.T: 21 |
OR: 79%(CR:60%) (Size ≤ 3 cm: 86%(CR:68%)) (Size >3 cm: 31% (CR: 8%)) |
30 lesions in the head and neck were treated in this study. | [65] |
| Gargiulo M et al. | 2012 | Retrospective | 25 | SCC: 13 (recurrent: 3) BCC: 9 (recurrent: 0) ADC: 2 (recurrent: 2) Bowen: 1 (recurrent: 1) |
Bleomycin | I.V | OR: 100%(CR:72%) (SCC:100%(CR:65%) (BCC:100%(CR:100%)) |
Four patients received surgery following ECT. | [77] |
| Mevio N et al. | 2012 | Retrospective | 15 | SCC: 13 (recurrent: 11) BCC: 1 (recurrent: 1) Merkel cell carcinoma: 1 (recurrent: 1) |
Bleomycin | I.V | OR: 94% (CR:61.5%) | Tumor response was evaluated according to the assessable lesion (n = 31). | [78] |
| Campana LG et al. | 2014 | Retrospective | 39 | SCC: 24 BCC: 9 ADC: 5 |
Bleomycin | I.V:7 I.T:7 I.V+I.T:25 |
OR: 59% (CR:38%) 1-year overall LPFS: 59% |
Site of tumor, Skin of the head and neck: 27 Oral cavity and oropharynx: 12 15 patients were treatment-naïve |
[79] |
| Landström FJ et al. | 2015 | Prospective | 19 | SCC: 18 AD: 1 |
Bleomycin | I.T | OR: 100% (CR:100%) 5-year local control in 12 surviving patients: 100% 5-year tumor-specific survival: 75% |
All patients had mucosal primary tumor (oral cavity or oropharynx). Two patients received ND concurrent with ECT. 12 patients received RT following ECT. |
[80] |
| Rotunno R et al. | 2016 | Phase II | 55 | Bleomycin | I.V | OR: 91% (CR:60%) [BCC in head and neck (CR:75%)] |
[81] | ||
| Bertino G et al. | 2016 | Prospective | 105 | SCC: 50 BCC: 34 MM: 10 Others: 11 |
Bleomycin | I.V: 97 I.T: 8 |
OR: 100% (CR:72%) (SCC:79% (CR:55%) (BCC:97% (CR:91%)) (MM:77% (CR:55%)) (Others: 44% (CR:0%)) 1-year overall DFS: 89% (SCC: 87%) (BCC: 100%) (MM: 89%) |
This study focused on skin HNCs. 28 patients were treatment-naïve Tumor response was evaluated according to the assessable lesion. |
[59] |
| Guida M et al. | 2016 | Retrospective | 19 | Angiosarcoma: 19 | Bleomycin | I.V | OR: 63% (CR:42%) 1-year DFS: 68% 1-year PFS: 45% |
This study focused on superficial angiosarcomas Five of 19 patients had scalp angiosarcoma |
[82] |
| Di Monta G et al. | 2017 | Retrospective | 22 | SCC:22 | Bleomycin | I.V | OR: 81.8% (CR:22.7%) | 18 of 22 patients had skin cancer of the head and neck. Seven patients received ECT ≥ 2 times. |
[83] |
| Plaschke CC et al. | 2017 | Phase II | 43 | SCC:39 ACC: 3 ADC: 1 |
Bleomycin | I.V: 2 I.T: 41 |
OR: 56% (CR:19%) 1-year OS: 54% 1-year LPFS: 54% |
This study focused on mucosal HNCs. 37 of 43 patients were evaluable for tumor response. |
[84] |
| Montuori M et al. | 2018 | Prospective | 15 | BCC SCC |
Bleomycin | I.V | OR: 100% (CR:100%) | [85] | |
| Groselj A et al. | 2018 | Prospective | 28 | BCC: 42 lesions SCC: 10 lesions [Standard dose: 12 patients] BCC: 17 lesions SCC: 7 lesions (Reduced dose: 16 patients) BCC: 25 lesions SCC: 3 lesions |
Bleomycin | I.V (standard dose):12 I.V (reduced dose):16 |
OR: Standard dose: 100% (CR:100%) (BCC:100%(CR:100%)) (SCC:100%(CR:100%) Reduced dose: 100% (CR:94%) (BCC:100%(CR:96%)) (SCC:100%(CR:100%) |
Patients with a primary recurrent skin cancer of the head and neck aged > 65 years old were enrolled. This study compared standard I.V dose bleomycin (15,000 IU/m2) and reduced dose (10, 000 IU/m2). Tumor response by histological type was evaluated according to the assessable lesion. |
[86] |
| Gargiulo M et al. | 2018 | Retrospective | 21 | SCC (lower lip): 21 | Bleomycin | I.V | OR: 100% (CR: 71.4%) | [87] | |
| Campana LG et al. | 2019 | Prospective | 20 | Angiosarcoma: 20 | Bleomycin | I.T | OR: 80% (CR:40%) Median OS: 12.5 months Median LPFS: 10.9 months |
This study focused on advanced cutaneous angiosarcomas. Seven of 20 patients had scalp/facial angiosarcoma. Combined with surgery in five patients. Concomitant systemic treatment in three patients. |
[88] |
| Longo F et al. | 2019 | Retrospective | 93 | SCC BCC Others |
Bleomycin | I.V | OR: 45% (CR:5%) Median OS: 9.1 months |
This study enrolled the HNC patients who had chemo and radio-refractory disease, having experienced at least two chemotherapy lines in addition to radiation therapy. | [89] |
| Pichi B et al. | 2019 | Prospective | 36 | SCC: 31 MM: 2 ADC: 1 Sarcoma: 1 Other: 1 |
Bleomycin | I.V | OR: 100% (CR:8.3%) 1-year OS: 41.6% Median OS: 9 months |
This study focused on patients with heavily pre-treated recurrent mucosal and cutaneous HNCs. | [90] |
| Plaschke CC et al. | 2019 | Phase II | 26 | SCC: 25 ACC: 1 |
Bleomycin | I.V | OR: 58% (CR:19%) | This study focused on recurrent mucosal HNCs. | [91] |
| Jamsek C et al. | 2020 | Prospective | 28 | BCC: 42 lesions SCC: 10 lesions (Standard dose: 16 patients] BCC: 25 lesions SCC: 3 lesions (Reduced dose: 12 patients) BCC: 17 lesions SCC: 7 lesions |
Bleomycin | I.V (standard dose):16 I.V (reduced dose):12 |
OR: Standard dose: CR:100% Reduced dose: CR:96% Tumor recurrence rate Standard dose (median follow-up of 28 months): 15.4% Reduced dose (median follow-up of 40 months): 39.0% |
Patients with primary recurrent skin cancer of the head and neck aged > 65 years old were enrolled. This study compared standard I.V dose bleomycin (15,000IU/m2) and reduced doses (10.000IU/m2) |
[92] |
| De Giorgi V et al. | 2020 | Prospective | 8 | BCC: 4 SCC: 3 Unknown: 1 |
Cisplatin | I.T | OR: 100% (CR:50%) | This study focused on skin cancer of the head and neck, except for cutaneous metastasis from breast cancer. Five patients were treatment-naïve |
[48] |
Abbreviations, N, number of patients; SCC, squamous cell carcinoma; ACC, adenoid cystic carcinoma; ADC, adenocarcinoma; MM, malignant melanoma; BCC, basal cell carcinoma; I.T, intratumoral injection; I.V, intravenous injection; OR, overall response; CR, complete response; LPFS, local progression-free survival; DFS, disease-free survival; PFS, progression-free survival; OS, overall survival. * The number indicates the number of patients who were treated with either I.V., I.T. or I.V. + I.T.