High-Risk Merkel Cell Carcinoma of the Skin Treated With Synchronous Carboplatin/Etoposide and Radiation: A Trans-Tasman Radiation Oncology Group Study—TROG 96:07

Abstract

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin.Patients and Methods: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m 2 days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients).Results: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control.Conclusion: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation.

Radiation monotherapy as regional treatment for lymph node‐positive Merkel cell carcinoma

“…Chemotherapy has been evaluated with disappointing results. A phase 2 study of concurrent and adjuvant cisplatin and etoposide in high-risk MCC patients initially reported favorable outcomes 48 ; however, an update with further analyses demonstrated no significant improvement in OS or DSS when compared with historical controls. 49 Given the known chemotherapyrelated morbidity and mortality in conjunction with no clear evidence of improved outcomes, adjuvant chemotherapy is currently not routinely recommended.…”

Expression of VEGF-A/C, VEGF-R2, PDGF-α/Β, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma

“…Owing to the rareness of the disease, very little data are available on the efficacy of chemotherapy and the results are conflicting. 4,5 Overall 5-year survival ranges from 31 to 74%. 6 Targeted anticancer therapies have been found to be very promising options in the treatment of different forms of cancer such as renal cell carcinoma 7,8 and gastrointestinal stromal tumors.…”

Digital Merkel cell carcinoma

“…There is increasing evidence for the use of adjuvant chemotherapy in stage II disease. The Trans-Tasman Radiation Oncology Group (21) demonstrated a 76% overall survival, with a protocol of synchronous chemoradiotherapy and adjuvant chemotherapy in a group of high-risk patients (two-thirds of whom had stage II disease) (21). In stage III disease, the presence of distant disease carries a grave prognosis.…”