Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: A Trans-Tasman Radiation Oncology Group study

Purpose: The acute and late toxicities of synchronous carboplatin, etoposid e, and radiation therapy were prospectively assessed in a group of patients with high-risk Merkel cell carcinoma of the skin. Patients and Methods: Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Tran s-Tasman Radiation Oncology Group. The trial was activated in 1996 and cont inues to accrue. Patients are eligible if they have disease localized to th e primary site and nodes and are required to have at least one of the follo wing high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, gross residual disease after surgery, or oc cult primary with nodes. Radiation was delivered to the primary site and no des to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carbop latin (area under curve [AUC] 4.5) and etoposide (80 mg/M-2 i.v.) were give n on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was 67 years (43-78). Results: The median duration of follow-up was 22 months (2-45). There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in 63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils with Grade 3 or 4 (neutrophils < 1 X 10(9)/L), occurring in 60% (95% CI 45, 75) of cases. Complications from neutropenia (fever and sepsis) occurred i n 16 patients (40% of cases). The median time for neutropenic complications was 27 days (9-35), and 10/16 (62%) cases of neutropenic fever occurred af ter the second cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets (<50 X 10(9)/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2, 15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of chemotherapy. There were no factors predictive for neutropenic toxicity at a p value < 0.05. Conclusions: The protocol has acceptable toxicity, and the treatment has be en deliverable in a multi-institutional trial setting. Neutropenia is likel y to occur with synchronous carboplatin/etoposide and radiation in this pop ulation of patients. The risk of a febrile neutropenia was greatest at the time of the second cycle of chemotherapy, when there was moist desquamation of skin or mucosal membranes that provided a portal for infection. This sh ould be considered in the design of subsequent protocols with chemoradiothe rapy. (C) 2001 Elsevier Science Inc.