A phase I study of pegylated liposomal doxorubicin and irinotecan in patients with solid tumors.
BACKGROUND
Preclinical studies have shown synergism between topoisomerase I and II inhibitors.


METHODS
We conducted a phase I study evaluating the combination of pegylated liposomal doxorubicin and irinotecan in patients with previously treated solid tumors.


RESULTS
Twelve patients were enrolled. The median age was 62 years (range 19-72). The most common grade 3/4 toxicities were neutropenia (dose-limiting toxicity), diarrhea and nausea/vomiting. The maximal tolerated dose and recommended schedule were pegylated liposomal doxorubicin 20 mg/m(2) over 60 min on day 1, followed by irinotecan 100 mg/m(2) over 90 min on days 1 and 8 of a 21-day cycle. There were no objective clinical responses, but 5 patients achieved stable disease lasting a median of 11 weeks duration (range 2-35).


CONCLUSIONS
This regimen should be further studied in patients with tumors known to have a sensitivity to both topoisomerase I and II inhibitors such as ovarian and small cell carcinoma.
Morgensztern
Daniel
D
Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Baggstrom
Maria Q
MQ
Pillot
Giancarlo
G
Tan
Benjamin
B
Fracasso
Paula
P
Suresh
Rama
R
Wildi
Jonathan
J
Govindan
Ramaswamy
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome; D055815:Young Adult
D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000077146:Irinotecan; D004317:Doxorubicin; D002166:Camptothecin