Gefitinib (ZD1839): therapy in selected patients with non-small cell lung cancer (NSCLC)?

PURPOSE: To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP). PATIENTS AND METHODS: A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed. RESULTS: In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers. CONCLUSIONS: In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.

Fractionated dose of cisplatin (CDDP) and vinorelbine (VNB) chemotherapy for elderly patients with advanced non-small cell lung cancer: phase II trial.

BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly representing about 30% of NSCLC patients over 70 years old. The aim of this study was to evaluate the response, survival and tolerability of a modified schedule with cisplatin-vinorelbine in elderly patients with advanced NSCLC. METHODS: Between November 2001 and March 2003, 30 patients were included into the study. Median age was 73 (range 70-77). Male/female 27/3 (90%/10%); 60% of patients were stage IV at diagnosis and only one patient presented with brain metastasis. Treatment consisted of cisplatin 30 mg/m(2) on days 1 and 8, and vinorelbine 25 mg/m(2) on days 1 and 8 every 21 days. RESULTS: A total of 120 cycles were administered with a median of four cycles per patient. The most relevant WHO toxicities were: neutropenia grade 3 in 6 (20%) patients and grade 4 in 13 (43%) patients. There were three (10%) treatment-related deaths: two caused by neutropenic fever and one due to acute pulmonary oedema. No other relevant hematological and non-hematological toxicities occurred. By intention-to-treat analysis, 10 patients (33%) showed stable disease and 10 patients (33%) showed a partial response while 10 patients (33%) showed treatment failure. Median survival time was 7.4 months; 1-year survival was 36.6% and median time to progression was 5.14 months. CONCLUSION: At this dose and schedule, the combination of vinorelbine and cisplatin obtained a response rate and survival comparable to the most active regimens. Non-hematologic toxicity was mild while neutropenia was the most relevant toxicity.

Second-line chemotherapy with weekly paclitaxel and gemcitabine in patients with small-cell lung cancer pretreated with platinum and etoposide: a single institution phase II trial.

PURPOSE: The safety and efficacy of a combined regimen of weekly paclitaxel and gemcitabine was tested in patients with refractory and sensitive small-cell lung cancer (SCLC). METHODS: Treatment consisted of paclitaxel 80 mg/m(2) on days 1, 8, 15 and gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks. Of the 31 patients enrolled, 10 had refractory and 21 had sensitive disease. Objective responses occurred in 8 patients (26%), including 2 out of 10 patients with refractory- and 6 out of 21 patients with sensitive SCLC. Median time to progression and median survival were 9.4 and 32 weeks, respectively. RESULTS: The schedule was very well tolerated, with grade 3-4 thrombocytopenia in 26% of the patients, grade 3 neutropenia in 26%, grade 3-4 asthenia in 13% and grade 1-2 sensory neuropathy in 32%. CONCLUSION: To conclude, this weekly schedule of paclitaxel and gemcitabine was found to have moderate activity in platinum-etoposide pretreated SCLC patients and a favorable toxicity profile.

Sequential chemotherapy of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in advanced non-small-cell lung cancer. A single institution phase II study.

BACKGROUND: To determine the activity and safety of a sequential regimen of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment was two cycles of cisplatin 80 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 3 weeks followed by two cycles of paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS: Fifty-five patients with inoperable NSCLC, performance status 2 or less were enrolled, including 19 patients with brain lesions. There were 23 partial responses (42%; 95% confidence interval 29-55). The median time to progression and overall survival were 5.8 and 10.3 months, respectively (6.5 and 12.8 in the patient subset without brain metastases). One-year survival rate was 47.5%. Grade III/IV neutropenia was the major side effect; it occurred in 56% of patients and was mainly limited to the first two chemotherapy cycles with cisplatin and vinorelbine. CONCLUSIONS: Sequential combination of cisplatin and vinorelbine followed by paclitaxel and gemcitabine is a manageable and active regimen for patients with NSCLC. It deserves to be tested against a standard two-drug scheme in a phase III trial.

A phase II trial of weekly paclitaxel and gemcitabine in non-small cell lung cancer patients previously treated with platinum and vinorelbine.

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.