title: A phase I-II study of bi-weekly gemcitabine and irinotecan as second-line chemotherapy in non-small cell lung cancer after prior taxane + platinum-based regimens.
abstract: OBJECTIVE
  Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC.
  
  
  METHODS
  Patients with advanced NSCLC, WHO-performance status (PS) </= 2, prior taxane/platinum-based chemotherapy were eligible. Chemotherapy was administered in a dose-escalated fashion in subgroups of 3-6 patients until dose-limiting toxicity (DLT) was encountered as follows: CPT-11 150 or 180 mg/m(2) followed by GEM 1,200-1,800 mg/m(2), both on days 1 + 15, recycled every 28 days in four dose levels (DLs).
  
  
  RESULTS
  Forty-nine patients entered the phase I and II part of the study (phase I: 12-phase II: 37 + 3 at DL-3), and 40 patients were evaluable for a response in phase II and all for toxicity: median age, 61 years (range 36-74); PS, 1 (0-2); gender, 43 males/6 females-histologies; adenocarcinoma, 25; squamous, 20; large cell, 4. Metastatic sites included lymph nodes, 38; bone, 5; liver, 4; brain, 3; lung nodules, 14; adrenals, 13; other, 3. All patients had prior taxane + platinum-based treatment, and 42 patients had prior docetaxel-ifosfamide-cisplatin/or-carboplatin regimens. DLT was observed at DL-4 and included 2/3 cases with grade 3 diarrhea-1/3 of these with febrile neutropenia. The recommended DL for phase II evaluation was DL3: GEM, 1,500 + CPT-11-180 mg/m(2). Objective responses in phase II were PR, 6/40 [15%; 95% confidence interval (CI), 5-31%]; stable disease, 16/40 (40%; 95% CI, 21-53%); and progressive disease, 18/40 (45%; 95% CI, 28.5-62.5%). The median time-to-progression was 4 months (range 1-12) and median survival 7 months (range 1.5-42 +), while 1-year survival was 20%. Grade 3/4 neutropenia was seen in 18% of patients (6% grade 4) and 6% incidence of febrile neutropenia. No Grade 3/4 thrombocytopenia were seen, grade 3 diarrhea in 6% of patients and grade 2 in 15% of patients, while other grade 3 non-hematologic toxicities were never encountered.
  
  
  CONCLUSIONS
  Bi-weekly GEM + CPT-11 is active and well tolerated in patients with advanced NSCLC failing prior taxane + platinum regimens, and represents an effective and convenient combination to apply in the palliative treatment of relapsed NSCLC particularly after failure of first-line docetaxel + platinum-based regimens.
authors.affiliation: Second Division of Medical Oncology, Department of Medicine, "Metaxa" Cancer Hospital, Piraues, 21 Apolloniou Street, 16341, Athens, Greece. ckosm@ath.forthnet.gr
authors.forename: Christos
authors.initials: C
authors.lastname: Kosmas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsavaris
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Syrigos
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.forename: George
authors.initials: G
authors.lastname: Tsakonas
authors.forename: Thomas
authors.initials: T
authors.lastname: Makatsoris
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mylonakis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karabelis
authors.forename: George P
authors.initials: GP
authors.lastname: Stathopoulos
authors.forename: Haralambos P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010349:Patient Compliance; D011788:Quality of Life; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine