Open, randomized, multi-center phase II study comparing efficacy and tolerability of Erlotinib vs. Carboplatin/Vinorelbin in elderly patients (>70 years of age) with untreated non-small cell lung cancer.

BACKGROUND: Targeting the epidermal-growth-factor-receptor (EGFR) in non-small cell lung cancer (NSCLC) is an established treatment option with less toxicity compared to conventional chemotherapy. This study was undertaken to determine whether Erlotinib is non-inferior compared to chemotherapy as a first-line therapy in unselected elderly patients. MATERIALS AND METHODS: Patients ≥ 70 years with untreated, metastatic NSCLC were randomized to Erlotinib (E), 150 mg/day or Carboplatin (AUC5) plus Vinorelbine (25mg/m(2) on days 1 and 8) every three weeks (CV). Primary endpoint was progression-free survival (PFS). After progression, crossover was strongly recommended. Secondary endpoints were duration of response, 1-year survival, overall survival (OS), response rate (RR), quality of life (FACT-L), assessment of comorbidities by simplified comorbidity score (SCS) and Charlsons' comorbidity score, safety and assessment of molecular markers. RESULTS: Between June 2006 and August 2008 284 pts were randomized to E (144) and CV (140). PFS was significantly inferior with E (median PFS 2.4 versus 4.6 months [HR 1.6, 75% CI 1.22-2.09, p: 0.0005]) as well as RR (7.8% v 28.3%, p: 0.0001). No significant difference in OS appeared (median E: 7.3 months versus CV: 8.4 months, HR: 1.24 [75% CI 0.9-1.71]). In never smokers PFS (median PFS: 3.7 v 4.3 m, E v CV, HR 0.72, 75% CI 0.35-1.48) and OS (median: 16.5 versus 17 months, HR 0.99 [75% CI 0.38-2.57]) were comparable. More skin toxicity and diarrhea was seen with E compared to more myelotoxicity, neurotoxicity and constipation with CV. Less severe adverse events were observed with E (81 v 102, E v CV). CONCLUSION: CV had an increased efficacy compared with E in an unselected population of elderly patients with advanced NSCLC.

Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer.

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Etoposide/vincristine-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: a prospective randomized phase III trial.

In the treatment of small cell lung cancer, carboplatin/etoposide/vincristine (CEV) is one of the most active regimens. In contrast, the etoposide/vincristine (EV) combination also has produced acceptable results in patients with extensive disease. To evaluate the efficacy and survival of patients treated with EV in comparison to those treated with more intensive CEV chemotherapy, a prospective, randomized, phase III trial was performed. The protocol for the treatment groups was as follows: treatment A (156 patients): carboplatin 300 mg/m2 day I, etoposide 140 mg/m2 days 1 through 3, and vincristine 1.4 mg/m2 days 1, 8, and 15; and treatment B (161 patients): etoposide 200 mg/m2 days 1 through 3 and vincristine 1.4 mg/m2 days 1 and 8. Chemotherapy cycles in each treatment arm were repeated every 4 weeks. Doses were reduced by 20% when hematologic or nonhematologic toxicity (grade 4) occurred. In all, 317 evaluable patients were treated. The overall response rate for patients treated with CEV was 79.8% compared with 59.8% for those treated with EV (P < .001). The median length of survival was 10 months for CEV-treated patients compared with 9 months for EV-treated patients (P = .19). Based on long-term survival rates, there was an advantage for the CEV-treated patients if they had good performance status, were younger than 60 years, had no distant metastases, and achieved a complete response to first-line therapy. We conclude that patients with poor prognostic factors (ie, poor performance status, multiple distant metastases, and less than partial response to the first cycle of chemotherapy) should appropriately be treated with the less aggressive two-drug combination chemotherapy. On the other hand, patients with good prognostic factors should be treated as aggressively as possible, and they will benefit from the more aggressive induction chemotherapy.