In a subsequent report, the same investigators evaluated a subset of these protocol patients (n = 40, after excluding patients with unknown primaries) and compared them with 61 historical controls who received no chemotherapy, were treated at the same institutions, were diagnosed before 1997, and underwent no routine imaging staging studies. Radiation was given to 50 patients. There was no significant survival benefit seen for chemotherapy patients.
In a subsequent, pilot, clinical trial of 18 patients from 2004 to 2006, the same investigators attempted to reduce the skin and hematological toxicity seen in Study 96-07. The drug schedule was changed to carboplatin (auc = 2) administered weekly during radiation beginning 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 was similar to the earlier trial. Early results suggest less toxicity, but other clinical outcomes have not yet been reported.
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. Median OS was 9 months for patients with metastatic disease and 24 months for patients with locally advanced disease. At 3 years, OS was projected to be 17% and 35%, respectively. Toxicity was significant, however, and without clear benefit, particularly in older patients.[Level of evidence: 3iiiDiii]
The most appropriate follow-up techniques and frequency for patients treated for MCC have not been prospectively studied. Given the propensity for local and regional recurrence, clinicians should perform at least a thorough physical examination of the site of initial disease and the regional nodes. Imaging studies may be ordered to evaluate signs and symptoms of concern, or they may be performed to identify distant metastases early; but, there are no data suggesting that early detection and treatment of new distant metastases results in improved survival.