Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study.
OBJECTIVE
The acute and late toxicities of synchronous carboplatin, etoposide, and radiation therapy were prospectively assessed in a group of patients with high-risk Merkel cell carcinoma of the skin.


METHODS
Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was activated in 1996 and continues to accrue. Patients are eligible if they have disease localized to the primary site and nodes and are required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary 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 curve [AUC] 4.5) and etoposide (80 mg/M(2) i.v.) were given 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 in 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 after 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 been deliverable in a multi-institutional trial setting. Neutropenia is likely to occur with synchronous carboplatin/etoposide and radiation in this population 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 should be considered in the design of subsequent protocols with chemoradiotherapy.
Poulsen
M
M
Division of Oncology Incorporating Queensland Radium Institute, Royal Brisbane Hospital, Herston, Queensland, Australia. M.Poulsen@mailbox.uq.edu.au
Rischin
D
D
Walpole
E
E
Harvey
J
J
Macintosh
J
J
Ainslie
J
J
Hamilton
C
C
Keller
J
J
Tripcony
L
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D015266:Carcinoma, Merkel Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005334:Fever / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology*; D011446:Prospective Studies; D011788:Quality of Life; D011855:Radiodermatitis / Q000209:etiology* / Q000473:pathology; D011879:Radiotherapy Dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
D005047:Etoposide; D016190:Carboplatin