Chemotherapy

A variety of chemotherapy regimens have been used for patients with MCC in the adjuvant, advanced, and recurrent therapy settings.[5,34,46,47] [Level of evidence C2] No phase III clinical trials have been conducted to demonstrate that adjuvant chemotherapy produces improvements in OS. However, some clinicians recommend its use in most cases because of the following factors:

When possible, patients can be encouraged to participate in clinical trials.

From 1997 to 2001, the Trans-Tasman Radiation Oncology Group performed a phase II evaluation of 53 patients with high-risk, local-regional MCC. High risk was defined as recurrence after initial therapy, involved lymph nodes, primary tumor larger than 1 cm, gross residual disease after surgery, or occult primary tumor with positive lymph nodes. Therapy included local-regional radiation therapy (50 Gy in 25 fractions), synchronous carboplatin (area under the curve [AUC], 4.5), and IV etoposide (89 mg/m2 on days 1–3 in weeks 1, 4, 7, and 10). Surgery was not standardized for either the primary tumor or the lymph nodes, and 12 patients had close margins, positive margins, or gross residual disease. Twenty-eight patients had undissected nodal beds, and the remainder had a variety of nodal surgeries. With a median follow-up of 48 months, the 3-year OS rate was 76%, the rate of local-regional control was 75%, and the rate of distant control was 76%. Radiation reactions in the skin and febrile neutropenia were significant clinical acute toxicities. Because of the heterogeneity of the population and the nonstandardized surgery, it is difficult to infer a clear treatment benefit from the chemotherapy.[48][Level of evidence C1]

In a subsequent report, the same investigators evaluated a subset of these protocol patients (n = 40, after excluding patients with unknown primary tumors). These patients were compared with 61 historical controls who received no chemotherapy, were treated at the same institutions, were diagnosed before 1997, and had no routine imaging staging studies. Radiation therapy was given to 50 patients. There was no significant survival benefit seen for chemotherapy patients.[49]

In a subsequent pilot clinical trial of 18 patients from 2004 to 2006, the same investigators attempted to reduce the skin and hematologic toxicity seen in Study 96-07. Carboplatin (AUC, 2) was administered weekly during radiation therapy beginning on day 1 for a maximum of five doses, followed by three cycles of carboplatin (AUC, 4.5; and IV etoposide 80 mg/m2 on days 1–3 beginning 3 weeks after radiation and repeated every 3 weeks for three cycles). The radiation therapy was similar to that in the earlier trial.[48] Results suggested a decrease in hematologic and skin toxicity.[50]

Use of chemotherapy has also been reported in selected patients with locally advanced and metastatic disease. In one retrospective study of 107 patients, 57% of patients with metastatic disease and 69% with locally advanced disease responded to initial chemotherapy. The median OS was 9 months for patients with metastatic disease and 24 months for patients with locally advanced disease. At 3 years, the OS rate was projected to be 17% for those with metastatic disease and 35% for those with locally advanced disease. Toxicity was significant, however, and without clear benefit, particularly in older patients.[51][Level of evidence C2]