title: Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis.
abstract: OBJECTIVE
  To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Eligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum creatinine concentration < or = 1.5 mg/dL, and bilirubin level < or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles.
  
  
  RESULTS
  From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSF and consistently remained < or = 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16 (30%) required packed RBC support. Neuropathy, myalgias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose was boosted to 215 mg/m2 in > or = 70% of patients who received three or more cycles. At an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%.
  
  
  CONCLUSIONS
  The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Langer
authors.forename: J C
authors.initials: JC
authors.lastname: Leighton
authors.forename: R L
authors.initials: RL
authors.lastname: Comis
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Dwyer
authors.forename: C A
authors.initials: CA
authors.lastname: McAleer
authors.forename: C A
authors.initials: CA
authors.lastname: Bonjo
authors.forename: P F
authors.initials: PF
authors.lastname: Engstrom
authors.forename: S
authors.initials: S
authors.lastname: Litwin
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced / Q000628:therapy; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D017239:Paclitaxel