CLINICAL INVESTIGATION Skin WEEKLY CARBOPLATIN REDUCES TOXICITY DURING SYNCHRONOUS CHEMORADIOTHERAPY FOR MERKEL CELL CARCINOMA OF SKIN MICHAEL POULSEN, F.R.A.N.Z.C.R.,* EUAN WALPOLE, F.R.A.C.P.,* JENNIFER HARVEY, F.R.A.N.Z.C.R.,* GRAEME DICKIE, F.R.A.N.Z.C.R., y PETER O’BRIEN, F.R.A.N.Z.C.R., z JACQUI KELLER, B.BUS. (H.I.M.), y LEE TRIPCONY, B.SC., y AND DANNY RISCHIN, F.R.A.N.Z.C.R. x * Division of Cancer Services, Princess Alexandra Hospital, University of Queensland and y Division of Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia; z Department of Radiation Oncology, Newcastle Mater Misericordia Hospital, Newcastle, NSW, Australia; and x Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia Purpose: The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and eto- poside was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was comparedwith the Trans-Tasman Radiation Oncology Group 96:07 study, which used iden- tical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. Patients and Methods: Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients en- tered into the Trans-Tasman Radiation Oncology Group 96:07 study. Results: Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Comparedwith the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. Conclusion: The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen. Ó 2008 Elsevier Inc. Merkel cell carcinoma, Chemoradiotherapy, Carboplatin, Etoposide. INTRODUCTION The value of chemotherapy in Stage I and II Merkel cell car- cinoma (MCC) of the skin remains controversial (1). It is pos- sible that chemotherapy could be potentially helpful in two ways. First, if given in conjunction with radiotherapy (RT), it might result in radiosensitization and improved levels of lo- coregional control. Second, it might reduce the incidence of distant spread by eradication of micrometastatic disease. De- spite a sound rationale, no randomized or historical data have yet documented a positive benefit from the addition of che- motherapy to local therapy, although a chemotherapy effect cannot be excluded (2). The Trans-Tasman Radiation Oncology Group (TROG) embarked on a Phase II study of synchronous chemoradio- therapy for high-risk MCC in 1996 (3). The overall survival and locoregional control were high for this group of patients with adverse prognostic factors, but the febrile neutropenia rate was 35% and Grade 3 or greater neutropenia occurred in 57% of the patients. Most cases of febrile neutropenia oc- curred in Week 5 of the RT, and it was postulated that the area of moist desquamation provided a portal for infection. To reduce the incidence of febrile neutropenia, we modi- fied the TROG 96:07 protocol to reduce the probability of making the patient neutropenic during the peak phase of the Reprint requests to: Michael Poulsen, F.R.A.N.Z.C.R., M.B. B.S., Department of Radiation Oncology, Mater Centre, 31 Raymond Tce, South Brisbane, QLD 4101 Australia. Tel: (07) 3840-3255; Fax: (07) 3840-3399; E-mail: michael_poulsen@ health.qld.gov.au Conflict of interest: none. Received Dec 13, 2007, and in revised form Feb 7, 2008. Accepted for publication Feb 14, 2008. 1070 Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 4, pp. 1070–1074, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter doi:10.1016/j.ijrobp.2008.02.076