Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling

Lung Cancer. 2001 Aug-Sep;33(2-3):267-75. doi: 10.1016/s0169-5002(01)00187-8.

Abstract

Background: Many regimens of gemcitabine-cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established.

Patients and methods: We conducted a phase II study with administration of cisplatin 50 mg/m(2) on days 1 and 8 and gemcitabine 800 mg/m(2) on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin.

Results: Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29-74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42-74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6-147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low.

Conclusion: This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia / chemically induced

Substances

  • Deoxycytidine
  • Cisplatin
  • Gemcitabine