title: A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer.
abstract: OBJECTIVE
  L-NDDP (Aroplatin) is a liposomal formulation of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a structural analogue of oxaliplatin. In a Phase 1 trial, the maximum tolerated dose (MTD) of L-NDDP was 312.5 mg/m2 with myelosuppression as dose limiting toxicity (DLT). We conducted a Phase 2 trial of L-NDDP in patients (pts) with advanced colorectal cancer (CRC) refractory to 5-fluorouracil/leucovorin or capecitabine and irinotecan to investigate the anti-tumor response of L-NDDP and to further characterize its toxicity profile in this population.
  
  
  METHODS
  L-NDDP was administered intravenously, once every 28 days. The starting dose was 300 mg/m2, with possible intra-patient dose escalation in the absence of grade 2 or higher drug-related toxicity. Patients were treated until disease progression or unacceptable toxicity. Of 20 eligible patients all were evaluable for toxicity and 18 were evaluable for response. Hematologic toxicities included anemia (grades 1-4) in 20% of pts and leucopenia, neutropenia and thrombocytopenia (grade 1/2) in 5% of patients each. Common non-hematologic toxicities included nausea (75%), vomiting (60%), and fatigue (70%), reversible infusion reactions (chest/back pain or shortness of breath; 40%), transient transaminase elevations (35%) and hyperbilirubinemia (20%). Grade 3-4 toxicities included infusion reaction (20%), vomiting (15%), fatigue (15%), anemia (10%) and ALT/AST elevation (5/15%). Peripheral neuropathy (grade 1/2) was seen in 15% of pts. One of 18 pts had a confirmed PR (5.6%), three (16.7%) had stable disease (> or =3 months) and 14 pts progressed. L-NDDP was well tolerated in this group of refractory patients and demonstrated evidence of anti-tumor activity.
  
  
  CONCLUSIONS
  Further studies of L-NDDP, preferably in combination with other agents such as fluoropyrimidines, are warranted.
authors.affiliation: Section of Hematology/Oncology, University Medical Center and Arizona Cancer Center, 1515 N Campbell Ave, PO Box 245024, Tucson, AZ 85724, USA. tdragovich@azcc.arizona.edu
authors.forename: Tomislav
authors.initials: T
authors.lastname: Dragovich
authors.forename: David
authors.initials: D
authors.lastname: Mendelson
authors.forename: Sandra
authors.initials: S
authors.lastname: Kurtin
authors.forename: Kelly
authors.initials: K
authors.lastname: Richardson
authors.forename: Daniel
authors.initials: D
authors.lastname: Von Hoff
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II)