title: Phase II trial of 9-nitrocamptothecin (RFS 2000) for patients with metastatic cutaneous or uveal melanoma.
abstract: The camptothecin derivative 9-nitrocamptothecin (9-NC) has demonstrated clinical activity in patients with ovarian and pancreatic carcinomas. Preclinical studies have shown promising activity of 9-NC for melanoma. We have thus conducted a phase II clinical trial of 9-NC for patients with metastatic cutaneous and uveal melanoma. Twenty-eight patients were enrolled in the trial, with diagnoses evenly divided between the two types of melanoma. 9-NC was administered orally at a starting dose of 1.5 mg/m(2)/day for 5 consecutive days of each week. No complete or partial responses were observed. Stabilization of disease was achieved in four individuals (15%) for durations of 3, 4, 6 and 8 months. Hematologic toxicity was moderate. Gastrointestinal side effects were common with 43% of the patients experiencing grade 3 or 4 diarrhea and 18% reporting grade 3 or 4 vomiting. In contrast to other 9-NC clinical trials, no patients developed chemical cystitis with gross hematuria. We conclude that, in keeping with the general chemoresistance of melanoma, 9-NC at the dose and schedule studied in this trial is significantly toxic and is not active for metastatic melanoma of cutaneous or uveal origin.
authors.affiliation: Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA. jaellerh@mail.mdanderson.org
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ellerhorst
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Smith
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Papadopoulos
authors.forename: Carl
authors.initials: C
authors.lastname: Plager
authors.forename: Omar
authors.initials: O
authors.lastname: Eton
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin