title: Salvage Treatment of Adrenocortical Carcinoma with Trofosfamide.
abstract: Adrenocortical carcinoma (ACC) has a dismal prognosis in advanced stages. Despite treatment with the adrenal toxicant mitotane and/or aggressive chemotherapy, tumor control is often short-lived. Here, we examine trofosfamide as a salvage treatment of ACC in an observational cohort study within the German ACC registry. Response defined as progression-free survival (PFS) at first tumor evaluation was assessed by RECIST 1.1 or clinically, and PFS and overall survival (OS) were estimated by the Kaplan-Meier method. Twenty-seven patients (11 males; median age 46.9 years) progressing after mitotane and three (median, range 0-5) other systemic treatments were evaluated for safety. Trofosfamide (150 mg/day) was administered as monotherapy (n = 13) or in combination with mitotane (n = 14). Overall tolerability was good with only mild adverse events. Six patients did not meet criteria for response assessment. Of the 21 patients, 8 patients had clinically progressive disease (3 deaths from ACC); among the 13 patients evaluable by RECIST 1.1, best response to treatment was stable disease (SD, n = 3) or progressive disease (n = 10). Hence, predefined response criteria were met in 3/21 patients (14 %). Median PFS was 84 days (95 % confidence interval 74-95) and median OS survival 198 days (95 % CI 89-307). One prolonged disease stabilization (best response by RECIST 1.1 -26 %) was observed for 479 days. In conclusion, trofosfamide is overall well tolerated but disease stabilization is rather rare. Accordingly, it may be used in selected cases of ACC not amenable to other treatment options such as clinical trials.
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. Kroiss_M@ukw.de.
authors.forename: Matthias
authors.identifier: 0000-0002-7628-3161
authors.initials: M
authors.lastname: Kroiss
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Deutschbein
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schlötelburg
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
authors.affiliation: Second Department of Medicine, Technical University of Munich, Munich, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Neu
authors.affiliation: Institut für Medizinische Biometrie und Epidemiologie, Philipps-Universität, Marburg, Germany.
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Müller
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine, Berlin, Germany.|Endocrinology in Charlottenburg, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.|Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Heidemeier
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.|Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; C003726:trofosfamide