title: A phase II trial of cyclosporin A in the treatment of refractory metastatic colorectal cancer.
abstract: Cyclosporin A (CSA) is an immunosuppressive agent that in experimental models has antiproliferative activity against colon cancer and other human neoplasms. A phase II trial was conducted to evaluate CSA in refractory colorectal malignancies. CSA was administered at a starting dose of 7.0 mg/kg twice daily (total dose, 14 mg/kg/day) and escalated to tolerance. Of 18 patients with measurable disease, 17 were evaluable. All had been treated with one fluorouracil-containing regimen. The European Cooperative Oncology Group (ECOG) performance status was 0 or 1 in 17 of the 18 patients. No objective responses were seen. Four patients maintained stable disease lasting from 10 to 75+ weeks. Significant toxicity occurred in 9 of 17 (53%) patients. Dose reduction was necessary in 10 of 17 (59%). Sustained escalation beyond the initial dose was possible in only two cases. Toxicities included nausea and vomiting (71%), nephrotoxicity (41%), fatigue (35%), flu-like symptoms (29%), and neurotoxicity (18%). In the dose and schedule employed in this trial, CSA is ineffective in refractory colorectal cancer and produces significant toxicity.
authors.affiliation: Department of Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: J R
authors.initials: JR
authors.lastname: Murren
authors.forename: S
authors.initials: S
authors.lastname: Ganpule
authors.forename: A
authors.initials: A
authors.lastname: Sarris
authors.forename: H
authors.initials: H
authors.lastname: Durivage
authors.forename: C
authors.initials: C
authors.lastname: Davis
authors.forename: R
authors.initials: R
authors.lastname: Makuch
authors.forename: R E
authors.initials: RE
authors.lastname: Handschumacher
authors.forename: J C
authors.initials: JC
authors.lastname: Marsh
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010534:Peritoneal Neoplasms / Q000556:secondary; D015996:Survival Rate
chemical_list: D003524:Cyclosporins; D003404:Creatinine