Abstract
Objective: The potential benefit of further chemotherapy approaches in patients with adrenocortical carcinoma (ACC) showing progressive disease after 2 chemotherapy lines is actually unknown. This study provides explorative information on the activity of metronomic chemotherapy in heavily pre-treated ACC patients. Design and methods: We tested the activity of cytotoxic treatments administered on a metronomic schedule in metastatic ACC patients showing disease progression after treatment with gemcitabine and capecitabine scheme. Results: Eight patients out of 28 consecutively enrolled in that trial were treated with several metronomic cytotoxic regimens. Six of them showed disease progression, but 2 patients obtained a clear benefit. The first patient was treated with oral etoposide (50 mg daily) as the 6th-line therapy and obtained a partial response lasting 24 months, while the second patient obtained a partial response lasting 10 months with metronomic oral cyclophosphamide (50 mg daily) as the 5th chemotherapy line. Both patients had sex hormone secreting tumors and were bearing a rather indolent ACC. Conclusions: The administration of several chemotherapy lines in advanced ACC patients cannot be routinely recommended outside prospective clinical trials. Few patients with indolent tumors, however, may benefit from this approach. According to our experience, oral cyclophosphamide and oral etoposide may be used in this setting.
Similar content being viewed by others
References
Crucitti F, Bellantone R, Ferrante A, Boscherini M, Crucitti P. The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multi-institutional series of 129 patients. The ACC Italian Registry Study Group. Surgery 1996, 119: 161–70.
Icard P, Goudet P, Charpenay C, et al. Adrenocortical carcinomas: surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons Study Group. World J Surg 2001, 25: 891–7.
Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 2006, 91: 2027–37.
Berruti A, Ferrero A, Sperone P, et al. Emerging drugs for adrenocortical carcinoma. Expert Opin Emerg Drugs 2008, 13: 497–509.
Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 2004, 4: 423–36.
Sperone P, Ferrero A, Daffara F, et al. Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second/third line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer 2010, 17: 445–53.
Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000, 92: 205–16.
Berruti A, Sperone P, Ferrero A, et al. Phase II study of weekly paclitaxel and sorafenib as second/third line therapy in patients with adrenocortical carcinoma. Eur J Endocrinol 2012, 166: 451–8.
Berruti A, Terzolo M, Sperone P, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma. A large prospective phase II trial. Endocr Relat Cancer 2005, 12: 657–66.
Lord R, Nair S, Schache A, et al. Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study. J Urol 2007, 177: 2136–40.
Borne E, Desmedt E, Duhamel A, et al. Oral metronomic cyclophosphamide in elderly with metastatic melanoma. Invest New Drugs 2010, 28: 684–9.
Hida K, Hida Y, Shindoh M. Understanding tumor endothelial cell abnormalities to develop ideal anti-angiogenic therapies. Cancer Sci 2008, 99: 459–66.
Emmenegger U, Francia G, Shaked Y, Kerbel RS. Metronomic chemotherapy: principles and lessons learned from applications in the treatment of metastatic prostate cancer. Recent Results. Cancer Res 2010, 180: 165–83.
Hermsen IG, Fassnacht M, Terzolo M, et al. Plasma concentrations of o,p’DDD, o,p’DDA, and o,p’DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study. J Clin Endocrinol Metab 2011, 96: 1844–51.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ferrero, A., Sperone, P., Ardito, A. et al. Metronomic chemotherapy may be active in heavily pre-treated patients with metastatic adreno-cortical carcinoma. J Endocrinol Invest 36, 148–152 (2013). https://doi.org/10.3275/8334
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3275/8334