title: A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer.
abstract: OBJECTIVE
  The efficacy and pharmacokinetics of paclitaxel when combined with altretamine for ovarian cancer were studied.
  
  
  METHODS
  A group of 30 patients, whose only chemotherapy was one or more cisplatin-based non-paclitaxel-containing regimens and whose ovarian cancer failed to respond or had relapsed within 6 months of their last platinum regimen, received paclitaxel as a 3-h intravenous infusion and altretamine given orally in four divided doses daily for 14 days repeated every 28 days. Doses were escalated from paclitaxel/altretamine 135/150 mg/m2 to 250/300 mg/m2 in cohorts of three patients.
  
  
  RESULTS
  The dose-limiting toxicities at 250/300 mg/m2 were WHO grade 3 myalgias and arthralgias in two patients and grade 3 lethargy, stomach cramps, peripheral neuropathy and vomiting in single patients. Considering all dose levels in cycle 1, 16 patients had grade 3 or 4 neutropenia but there was only one episode of febrile neutropenia. Other grade 3 toxicities were vomiting in four patients, myalgias in three, peripheral neuropathy in two and lethargy in two. Grade 3 alopecia occurred in 23 patients. Three patients achieved a complete response and 12 achieved a partial response for an overall objective response rate of 50%. Responses occurred at all dose levels of 175/150 mg/m2 and higher. The median freedom from progression was 35 weeks, with a median survival of 55 weeks. Altretamine did not alter the pharmacokinetics of paclitaxel and there were no consistent differences in paclitaxel pharmacokinetic parameters or toxicities between course 1 and 2. No dose-response relationships were evident above paclitaxel/altretamine 175/150 mg/m2.
  
  
  CONCLUSIONS
  Paclitaxel and altretamine can be safely combined and with a high response rate in relapsed ovarian cancer, justifying further studies with this combination.
authors.affiliation: Royal Adelaide Hospital Cancer Centre, North Terrace, South Australia. iolver@medicine.adelaide.edu.au
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: M
authors.initials: M
authors.lastname: Davy
authors.forename: D
authors.initials: D
authors.lastname: Lüftner
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Egorin
authors.forename: A
authors.initials: A
authors.lastname: Ellis
authors.forename: L
authors.initials: L
authors.lastname: Webster
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D006585:Altretamine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D006585:Altretamine