title: Phase I clinical trial of topotecan and pegylated liposomal doxorubicin.
abstract: BACKGROUND
  The objective of this study was to determine the feasibility and maximum tolerated dose (MTD) of combination topotecan and pegylated liposomal doxorubicin (PLD) administered in 4- or 3-week cycles in patients with advanced or refractory solid tumors.
  
  
  METHODS
  Patients were treated with intravenous topotecan (0.75-1.25 mg/m2) for 3 days followed by PLD (25-40 mg/m2) on Day 4. The following dose combinations (topotecan/PLD, mg/m2) were explored: 0.75/40, 1.0/40, and 1.25/40 every 28 days; and 1.0/25 and 1.0/30 every 21 days.
  
  
  RESULTS
  Thirty-two patients were enrolled, and all had received prior chemotherapy. Most (84 percent) patients had ovarian cancer. A total of 157 cycles (median, 4 cycles; range, 1-19 cycles) of chemotherapy were administered. Dose-limiting toxicities were Grade 4 neutropenia and death at dose level 3 (1.25/40 mg/m2 every 28 days), and neutropenic fever, Grade 3 stomatitis, and Grade 3 peripheral neuropathy (all in one patient) at dose level 5 (1/30 mg/m2 every 21 days). Myelosuppression was the most common serious toxicity. Twenty-six patients were evaluable for response and 7 (27 percent) had partial responses. All responses were seen in patients with ovarian cancer.
  
  
  CONCLUSIONS
  This combination is feasible and well tolerated; encouraging activity was observed in heavily pretreated patients with ovarian cancer. The recommended regimens for a Phase II study are topotecan 1.0 mg/m2 on Days 1-3 followed by PLD 40 mg/m2 on Day 4 of a 28-day cycle, and topotecan 1.0 mg/m2 on Days 1-3 and PLD 30 mg/m2 on Day 4 of a 21-day cycle.
authors.affiliation: Division of Medical Oncology, University of Southern California Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90048, USA. agustin.garcia@cshs.org
authors.forename: Agustin A
authors.initials: AA
authors.lastname: Garcia
authors.forename: Lynda
authors.initials: L
authors.lastname: Roman
authors.forename: Laila
authors.initials: L
authors.lastname: Muderspach
authors.forename: Anne
authors.initials: A
authors.lastname: O'meara
authors.forename: Grace
authors.initials: G
authors.lastname: Facio
authors.forename: Susan
authors.initials: S
authors.lastname: Edwards
authors.forename: Alexander
authors.initials: A
authors.lastname: Burnett
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin