Chemotherapy (Primary and Recurrent Disease)
Chemotherapy has shown activity in Merkel cell carcinoma (MCC) in the neoadjuvant, adjuvant, and metastatic/recurrent setting, but responses are not durable and toxicity is not insignificant, especially in a patient population where the median age at diag
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Rupali Roy and Timothy M. Kuzel
The role of systemic chemotherapy for Merkel cell carcinoma (MCC) has been poorly defined as few prospective, and no randomized clinical trials have been conducted due to the relative rarity of this disorder. However, the literature regarding chemotherapy in MCC does provide evidence that this entity is chemosensitive. Thus, most of the data regarding chemotherapeutics comes from retrospective analyses at single institutions. Though most institutions consider chemotherapy and/or surgery and/or radiation therapy for stage IV disease as reasonable, the role in this setting and the use of chemotherapy in the neoadjuvant or adjuvant setting for early stage or node positive disease remains controversial.
Chemotherapy for Metastatic Disease A number of single agent and combination chemotherapy regimens have been shown to be active in MCC. Two of the most commonly
R. Roy Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital, C367 Med Inn Building, 1500 East Medical Center Drive, SPC 5848, Ann Arbor, MI 48109-5848, USA e-mail: [email protected]; [email protected] T.M. Kuzel (*) Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine of Northwestern University, 676 N Saint Clair St Suite 850, Chicago, IL 60611, USA e-mail: [email protected]
used regimens are cisplatin or carboplatin with or without etoposide and cyclophosphamide with doxorubicin (or epirubicin) and vincristine. Other agents that have been used alone or in combination successfully include ifosfamide [1], 5-fluorouracil [2], methotrexate [2], topotecan [3], dacarbazine [4], and liposomal doxorubicin [5]. Responses, however, are relatively short-lived, and toxicity is not negligible in a patient population where the median age at diagnosis is 69. Voog et al. reviewed the literature and reported the outcomes of 107 patients with either locally advanced or metastatic MCC treated with chemotherapy [6]. Cyclophosphamide or ifosfamidecontaining regimens were given to 56 % of patients, anthracycline-containing regimens to 49 %, platinum-containing regimens to 25 %, 5FU-containing regimens to 13 %, and other regimens to 12 %. The overall response rate (ORR) for first-line chemotherapy was 61 %. There was no significant difference in ORR between locally advanced and metastatic tumors, which was 69 % and 57 %, respectively. Though the response rates observed with the different types of chemotherapy regimens ranged from 43 % to 100 %, none was associated with significantly superior survival. The median duration of response was 8 months, and the median overall survival (OS) from the date of initiation of chemotherapy was 24 months for patients with locally advanced disease and 9 months for patients with metastatic disease. Overall survival was significantly better in patients who had locally advanced disease and in those patients who achieved a CR after first-line chemotherapy.
M. Alam et al. (eds.), Merkel Cell Carcinoma, DOI 10.1007/978-1-4614-
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