Combination of docetaxel and cetuximab for penile cancer

Abstract

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel-cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.

Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations

“…Previously, anecdotal reports have described striking clinical benefit with cetuximab in patients with PSCC. For these patients, pretreatment testing of EGFR expression was performed with immunohistochemistry, which is qualitative at best, and it is also likely biased by the nonreporting of failure of cetuximab treatment in PSCC [6][7][8]. The frequency of 20% of patients with PSCC in this series harboring EGFR high-level amplification suggests that the basis of occasional benefit from cetuximab is indeed linked to EGFR amplification.…”

“…For metastatic disease, TIP is also the preferred first-line regimen, although historical regimens such as 5-fluorouracil with cisplatin may also be considered [5]. Cetuximab has been seen to be active in a subset of patients with PSCC; one patient in one non-epidermal growth factor receptor (EGFR)-stratified series had a response rate of 23.5% to cetuximab with chemotherapy backbone [6][7][8]. EGFR expression was assayed in four other patients, with a range from 11 to 31, but expression did not correlate well with response [6][7][8].…”

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

“…Taken altogether, these data suggest that locally advanced or metastatic cSCC can indeed be amenable to therapies targeting the EGFR, either alone or combined with conventional chemotherapy and/or radiotherapy whenever it is possible in these fragile patients, an option that is likely to be extended to penile SCC where cetuximab seems equally efficient in patients with locally advanced or metastatic diseases [32]. The optimal combination is still to be determined, considering that other molecules than platinum salts and 5-fluorouracil have been proposed including capecitabine [33] and docetaxel [34,35]. …”

The epidermal growth factor receptors as biological targets in penile cancer

“…The RASSF1A protein is expressed in all nonmalignant epithelial cells and it exerts its tumor-suppressor activity via RAS-mediated apoptosis. Promoter CpG island 63 0 Cetuximab + cisplatin Yes 4.5 1 [11] 62 1 Cetuximab + cisplatin Yes 3.5 1 [11] 59 1 Cetuximab + cisplatin Yes 3.1 1 [11] 45 4 Cetuximab + cisplatin Yes 3.2 1 [12] 36 0 Cetuximab + TIP Yes 2.8 1 [12] 59 1 Cetuximab + TIP Yes 6.3 1 [12] 68 1 Cetuximab + TIP Yes 2.4 1 [10] 75 1 Docetaxel + cetuximab Yes 7 1 [14] 59 3 Nimotuzumab + paclitaxel Yes 5.75 0 [13] 44 0 Nimotuzumab + paclitaxel + cisplatin Yes 5.5 1 [9] 58 1 Panitumumab Yes 3 0 [11] 43 2 Panitumumab + cisplatin Yes 6 1 hypermethylation in penile cancer is the major mechanism for RASSF1A inactivation, which appears to be closely related to RAS activation in human cancers. RASSF1A was frequently inactivated in tumor types without RAS gene mutations, such as small cell lung cancer, nasopharyngeal cancer and neuroendocrine pancreatic tumor, which implicates that RASSF1A inactivation may drive or facilitate RAS activation, even in the absence of RAS mutations [6,7].…”

“…Combination of MEHD7945A with chemotherapy was also feasible [8]. A number of anti-EGFR agents have been used in penile cancer patients outside the context of a clinical trial, mainly as a salvage treatment after failure of first-line chemotherapy [9][10][11][12][13][14]. Monoclonal antibodies appear to have promising efficacy, whereas currently available EGFR inhibitors such erlotinib and gefitinib seem to have no activity, which is likely to be related to the lack of EGFR mutating activation [11].…”