Eruptive cutaneous squamous cell carcinoma and psoriasis: response to cetuximab

Abstract

Cutaneous squamous cell carcinomas (CSCCs) comprise 20-30% of nonmelanoma skin cancers (NMSCs), and continue to increase in incidence. We report a case of a patient with severe psoriasis who had recurrent and eruptive CSCCs on her leg, which were successfully treated with cetuximab and radiotherapy. The patient had successful long-term clearance of her skin tumours, with the additional finding of resolution of psoriasis while on cetuximab therapy.

Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients

“…Cetuximab has not been specifically developed in cSCC and no RCT has been conducted in this setting, but a number of individual case reports and some series, most often with a retrospective design, have been previously published to date in this indication (Table 4) [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. The most relevant report is probably a multicenter phase II study of cetuximab in monotherapy for unresectable locally advanced or metastatic cSCC [27] that analyzed 31 finally assessable patients with ORR and DCR of 13 and 81%, respectively, in per-protocol analysis.…”

“…In this setting, cetuximab, a chimeric human monoclonal antibody binding competitively and with high affinity to the EGFR, prevents receptor stimulation by endogenous ligands and inhibits proliferation, enhances apoptosis, and reduces angiogenesis, invasiveness, and metastatic spreading in target tissues. By analogy with advanced head and neck SCC where it proved efficient alone or associated with radiotherapy and/or chemotherapy [4,5,6,7], a number of case reports, small series reports [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26], and scarce clinical trials or larger series [27,28,29] recently suggested that cetuximab may help control metastatic or locally advanced, unresectable cSCC, either alone or in combination with other therapies including systemic chemotherapy and/or radiotherapy. In order to add further information regarding its interest in advanced cSCC, the efficacy and safety of cetuximab alone or combined with chemotherapy in patients with locally advanced and metastatic cSCC treated at our institution were retrospectively analyzed.…”

Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients

“…Cetuximab has not been specifically developed in cSCC and no RCT has been conducted in this setting, but a number of individual case reports and some series, most often with a retrospective design, have been previously published to date in this indication (Table 4) [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. The most relevant report is probably a multicenter phase II study of cetuximab in monotherapy for unresectable locally advanced or metastatic cSCC [27] that analyzed 31 finally assessable patients with ORR and DCR of 13 and 81%, respectively, in per-protocol analysis.…”

“…In this setting, cetuximab, a chimeric human monoclonal antibody binding competitively and with high affinity to the EGFR, prevents receptor stimulation by endogenous ligands and inhibits proliferation, enhances apoptosis, and reduces angiogenesis, invasiveness, and metastatic spreading in target tissues. By analogy with advanced head and neck SCC where it proved efficient alone or associated with radiotherapy and/or chemotherapy [4,5,6,7], a number of case reports, small series reports [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26], and scarce clinical trials or larger series [27,28,29] recently suggested that cetuximab may help control metastatic or locally advanced, unresectable cSCC, either alone or in combination with other therapies including systemic chemotherapy and/or radiotherapy. In order to add further information regarding its interest in advanced cSCC, the efficacy and safety of cetuximab alone or combined with chemotherapy in patients with locally advanced and metastatic cSCC treated at our institution were retrospectively analyzed.…”

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

“…Both of these ligands are known to be overexpressed in psoriasis lesions . However, to date, no significant genetic signals for psoriasis have mapped to the EGFR or its ligands, and biological and pharmacological EGFRIs have by and large failed to improve psoriasis . Nevertheless, the striking inflammatory and hyperplastic skin phenotypes manifested by two strains of AREG TG mice , coupled with the marked overexpression of AREG and other EGFR ligands in psoriatic lesions, prompted us to further explore the biological outcomes following KC‐specific overexpression of hAREG in TG mice.…”

A case of psoriasis pustolosa palmaris induced by cetuximab

“…In addition, antipsoriatic vitamin D3 derivatives are able to inhibit the expression of EGFR in human epidermal keratinocytes 6. Moreover, some authors reported marked improvement of psoriasis during cetuximub monotherapy for the treatment of colon cancer and eruptive skin squamous cell carcinomas 7–10. Therefore, it is plausible that cetuximab may induce remission of psoriasis in these patients through regulation of abnormal EGFR expression.…”

Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients

“…Cetuximab has not been specifically developed in cSCC and no RCT has been conducted in this setting, but a number of individual case reports and some series, most often with a retrospective design, have been previously published to date in this indication (Table 4) [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. The most relevant report is probably a multicenter phase II study of cetuximab in monotherapy for unresectable locally advanced or metastatic cSCC [27] that analyzed 31 finally assessable patients with ORR and DCR of 13 and 81%, respectively, in per-protocol analysis.…”

“…In this setting, cetuximab, a chimeric human monoclonal antibody binding competitively and with high affinity to the EGFR, prevents receptor stimulation by endogenous ligands and inhibits proliferation, enhances apoptosis, and reduces angiogenesis, invasiveness, and metastatic spreading in target tissues. By analogy with advanced head and neck SCC where it proved efficient alone or associated with radiotherapy and/or chemotherapy [4,5,6,7], a number of case reports, small series reports [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26], and scarce clinical trials or larger series [27,28,29] recently suggested that cetuximab may help control metastatic or locally advanced, unresectable cSCC, either alone or in combination with other therapies including systemic chemotherapy and/or radiotherapy. In order to add further information regarding its interest in advanced cSCC, the efficacy and safety of cetuximab alone or combined with chemotherapy in patients with locally advanced and metastatic cSCC treated at our institution were retrospectively analyzed.…”

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

“…Both of these ligands are known to be overexpressed in psoriasis lesions . However, to date, no significant genetic signals for psoriasis have mapped to the EGFR or its ligands, and biological and pharmacological EGFRIs have by and large failed to improve psoriasis . Nevertheless, the striking inflammatory and hyperplastic skin phenotypes manifested by two strains of AREG TG mice , coupled with the marked overexpression of AREG and other EGFR ligands in psoriatic lesions, prompted us to further explore the biological outcomes following KC‐specific overexpression of hAREG in TG mice.…”

A case of psoriasis pustolosa palmaris induced by cetuximab

“…In addition, antipsoriatic vitamin D3 derivatives are able to inhibit the expression of EGFR in human epidermal keratinocytes 6. Moreover, some authors reported marked improvement of psoriasis during cetuximub monotherapy for the treatment of colon cancer and eruptive skin squamous cell carcinomas 7–10. Therefore, it is plausible that cetuximab may induce remission of psoriasis in these patients through regulation of abnormal EGFR expression.…”

Efficacy and Tolerance of Cetuximab Alone or Combined with Chemotherapy in Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: An Open Study of 14 Patients

“…Cetuximab has not been specifically developed in cSCC and no RCT has been conducted in this setting, but a number of individual case reports and some series, most often with a retrospective design, have been previously published to date in this indication (Table 4) [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. The most relevant report is probably a multicenter phase II study of cetuximab in monotherapy for unresectable locally advanced or metastatic cSCC [27] that analyzed 31 finally assessable patients with ORR and DCR of 13 and 81%, respectively, in per-protocol analysis.…”

“…In this setting, cetuximab, a chimeric human monoclonal antibody binding competitively and with high affinity to the EGFR, prevents receptor stimulation by endogenous ligands and inhibits proliferation, enhances apoptosis, and reduces angiogenesis, invasiveness, and metastatic spreading in target tissues. By analogy with advanced head and neck SCC where it proved efficient alone or associated with radiotherapy and/or chemotherapy [4,5,6,7], a number of case reports, small series reports [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26], and scarce clinical trials or larger series [27,28,29] recently suggested that cetuximab may help control metastatic or locally advanced, unresectable cSCC, either alone or in combination with other therapies including systemic chemotherapy and/or radiotherapy. In order to add further information regarding its interest in advanced cSCC, the efficacy and safety of cetuximab alone or combined with chemotherapy in patients with locally advanced and metastatic cSCC treated at our institution were retrospectively analyzed.…”

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

“…Both of these ligands are known to be overexpressed in psoriasis lesions . However, to date, no significant genetic signals for psoriasis have mapped to the EGFR or its ligands, and biological and pharmacological EGFRIs have by and large failed to improve psoriasis . Nevertheless, the striking inflammatory and hyperplastic skin phenotypes manifested by two strains of AREG TG mice , coupled with the marked overexpression of AREG and other EGFR ligands in psoriatic lesions, prompted us to further explore the biological outcomes following KC‐specific overexpression of hAREG in TG mice.…”

A case of psoriasis pustolosa palmaris induced by cetuximab

“…In addition, antipsoriatic vitamin D3 derivatives are able to inhibit the expression of EGFR in human epidermal keratinocytes 6. Moreover, some authors reported marked improvement of psoriasis during cetuximub monotherapy for the treatment of colon cancer and eruptive skin squamous cell carcinomas 7–10. Therefore, it is plausible that cetuximab may induce remission of psoriasis in these patients through regulation of abnormal EGFR expression.…”