title: NCIC CTG IND.190 phase I trial of dalotuzumab (MK-0646) in combination with cisplatin and etoposide in extensive-stage small-cell lung cancer.
abstract: The insulin-like growth factor receptor is a potential target in small-cell lung cancer. We conducted a phase I study of cisplatin, etoposide plus dalotuzumab. Two dose levels of dalotuzumab (DL1 5 mg/kg, DL2 10mg/kg IV weekly) were evaluated in combination with cisplatin (25 mg/m²) and etoposide (100 mg/m²) IV D1-3, every 21 days, for patients with chemotherapy-naive extensive-stage small-cell lung cancer. Primary outcome was determination of the recommended phase 2 dose. Secondary outcomes included response rate and toxicity. Twelve patients were treated (DL1, 3 and DL2, 9). The median age was 63 years (48-70), with six males and six females. The majority of patients were Eastern Cooperative Oncology Group 1 and had four or more sites of disease. No dose-limiting toxicities were observed in DL1 or DL2, although one patient died from neutropenic sepsis in an expanded cohort at DL2. The recommended phase 2 dose of dalotuzumab was 10 mg/kg/week. The confirmed objective response rate was 67% (partial response 8, stable disease 2, progressive disease 1, nonevaluable 1). Grade 3 or higher toxicities (any cycle) occurring in more than one patient included: neutropenia (92%); thrombocytopenia (25%); leukopenia (50%); anemia (17%); fatigue (33%); joint pain (17%); thrombosis (25%). Grade 2 or 3 hyperglycemia was observed in one of three (DL1) and five of nine (DL2) patients. Eight serious adverse events (thrombosis, febrile neutropenia, infection, syncope, fatigue [2], dyspnea, back pain) were observed in three patients. Dalotuzumab can be combined at full dose with standard doses of cisplatin and etoposide. The observed toxicities are consistent with that expected from cisplatin and etoposide except for hyperglycemia, which seems to be dose dependent.
authors: *Department of Oncology, McMaster University, Juravinski Cancer Centre, Hamilton Ontario, Canada; †Medical Oncology Department, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; ‡Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada; and §NCIC CTG Queens University, Kingston, Ontario, Canada.
authors: Peter M
authors: PM
authors: Ellis
authors: Frances A
authors: FA
authors: Shepherd
authors: Scott A
authors: SA
authors: Laurie
authors: Glenwood D
authors: GD
authors: Goss
authors: Martin
authors: M
authors: Olivo
authors: Jean
authors: J
authors: Powers
authors: Lesley
authors: L
authors: Seymour
authors: Penelope A
authors: PA
authors: Bradbury
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005047:Etoposide; C569480:dalotuzumab; D002945:Cisplatin