title: The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.
abstract: The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.
authors.affiliation: Department of Neurology, Dr. Daniel den Hoed Cancer Center, University Hospital Rotterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van Gerven
authors.forename: A
authors.initials: A
authors.lastname: Hovestadt
authors.forename: J W
authors.initials: JW
authors.lastname: Moll
authors.forename: C J
authors.initials: CJ
authors.lastname: Rodenburg
authors.forename: T A
authors.initials: TA
authors.lastname: Splinter
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: L
authors.initials: L
authors.lastname: Keizer
authors.forename: T E
authors.initials: TE
authors.lastname: Drogendijk
authors.forename: C M
authors.initials: CM
authors.lastname: Groenhout
authors.forename: C J
authors.initials: CJ
authors.lastname: Vecht
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D012684:Sensory Thresholds; D013736:Testicular Neoplasms / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin