title: A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer.
abstract: The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated antitumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status > or = 70%, age > or = 18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500 mg/m2 by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1-6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/microl (116-16,374/microl) and 276 x 10(3)/ microl (5-769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted.
authors.affiliation: Department of Oncology, Montefiore Medical Center, Bronx, NY 10461, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Goel
authors.forename: Scott
authors.initials: S
authors.lastname: Wadler
authors.forename: Anthony
authors.initials: A
authors.lastname: Hoffman
authors.forename: Fabio
authors.initials: F
authors.lastname: Volterra
authors.forename: Cheryl
authors.initials: C
authors.lastname: Baker
authors.forename: Elliot
authors.initials: E
authors.lastname: Nazario
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Alyson
authors.initials: A
authors.lastname: Silverman
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005960:Glucosides; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000970:Antineoplastic Agents; D002227:Carbazoles; D005960:Glucosides; C093269:becatecarin