title: Phase I study of escalating doses of oxaliplatin in combination with fixed dose gemcitabine in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  Oxaliplatin (OHP) is a new platinum antineoplastic, while gemcitabine (GEM) is one of the most active drugs against non-small cell carcinoma (NSCLC). The OHP/GEM combination is interesting because the drugs have different mechanisms of action and toxicity profiles. The primary endpoint of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OHP/GEM combination in non-small cell carcinoma of the lung.
  
  
  METHODS
  Patients with relapsed NSCLC were treated with fixed dose i.v. GEM (1250 mg/m2) on days 1 and 8; followed on day 1 by i.v. OHP over 3 h, starting from 70 mg/m2 with 20 mg/m2 increments, up to 130 mg/m2. We enrolled 19 patients with eastern cooperative oncology group (ECOG) status 0/1=13/6; male/female=13/6. All had received first-line and four second-line chemotherapy.
  
  
  RESULTS
  Four patients dropped out. At dose level 2, one patient died of pulmonary embolism; at level 3, two patients died of disease progression. One patient at level 3, refused to continue treatment after allergic reaction (high fever episode) during infusion of third cycle. Fifteen patients were evaluable for toxicity and response. According to a priori statistical considerations, three patients in each of the first three treatment levels and six in the last level were evaluable. No G3-4 toxicity was observed at levels 1 and 2. G3 neutropenia and anemia occurred in 8% of cycles at level 3. Six patients entered level 4 (OHP 130 mg/m2) with 22 courses delivered: G3-4 neutropenia occurred in 9%, G1-2 thrombocytopenia in 18%; other toxicities were mainly limited to G1-2 flu-like syndrome in about one third of patients and G1-2 nausea and vomiting in 5% of courses. There was no myelo-DLT at the highest dose level. There was no neurotoxicity at any level. Treatment was delayed in 12% and dose reduced in 26% of courses. There were 2/15 PR.
  
  
  CONCLUSIONS
  MTD was not reached. OHP and GEM can probably be administered safely at 130 and 1250 mg/m2, respectively, as first-line therapy. The schedule is being used in a phase II trial.
authors.affiliation: Medical Oncology Unit B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, Milano 20133, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bidoli
authors.forename: Simonetta C
authors.initials: SC
authors.lastname: Stani
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Daniela
authors.initials: D
authors.lastname: De Candis
authors.forename: Diego
authors.initials: D
authors.lastname: Cortinovis
authors.forename: Stefania
authors.initials: S
authors.lastname: Aglione
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zilembo
authors.forename: Luisa
authors.initials: L
authors.lastname: Toffolatti
authors.forename: Barbara
authors.initials: B
authors.lastname: Formisano
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D013921:Thrombocytopenia / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine