Rogerio Lilenbaum

Phase II Trial of Cetuximab in Patients With Previously Treated Non–Small-Cell Lung Cancer

PURPOSEnTo determine the efficacy of cetuximab in patients with recurrent or progressive non-small-cell lung cancer (NSCLC) after receiving at least one prior chemotherapy regimen.nnnPATIENTS AND METHODSnThis was an open-label, phase II study of patients with epidermal growth factor receptor (EGFR) -positive and EGFR-negative advanced NSCLC with Eastern Cooperative Oncology Group performance status 0 to 1. Patients received cetuximab 400 mg/m2 intravenously (IV) during 120 minutes on week 1 followed by weekly doses of cetuximab 250 mg/m2 IV during 60 minutes. A cycle was considered as 4 weeks of treatment and therapy was continued until disease progression or intolerable toxicities. The primary end point was to assess response rate. Secondary end points included an estimation of time to progression and survival.nnnRESULTSnPatient and disease characteristics (n = 66) included EGFR-positive status (n = 60); EGFR-negative status (n = 6); number of prior regimens (one, n = 28; two, n = 27; > or = three, n = 11); male (n = 41); female (n = 25); adenocarcinoma (n = 36); and smoking status (never, n = 13; former, n = 45; current, n = 8). Grade 3/4 toxicities included acne-like rash (6.1%), anaphylactic reactions (1.5%), and diarrhea (1.5%). The response rate for all patients (n = 66) was 4.5% (95% CI, 0.9% to 12.7%) and the stable disease rate was 30.3% (95% CI, 19.6% to 42.9%). The response rate for patients with EGFR-positive tumors (n = 60) was 5% (95% CI, 1.0% to 13.9%). The median time to progression for all patients was 2.3 months (95% CI, 2.1 to 2.6 months) and median survival time was 8.9 months (95% CI, 6.2 to 12.6 months).nnnCONCLUSIONnAlthough the response rate with single-agent cetuximab in this heavily pretreated patient population with advanced NSCLC was only 4.5%, the disease control rates and overall survival seem comparable to that of pemetrexed, docetaxel, and erlotinib in similar groups of patients.

Prevalence of Poor Performance Status in Lung Cancer Patients: Implications for Research

Introduction: Performance status (PS) is a standard functional classification in oncology research and practice. However, despite its widespread use, little is known about the prevalence of poor PS in lung cancer patients, in relation to other cancers, based on the assessments of health care providers and patients. Methods: Data from two quality of life studies were pooled for analysis. Analyses were performed on the subset of patients with lung cancer (n = 503) from the entire population of cancer patients (n = 2885). The prevalence of poor PS (defined as PS = 2–4 on a 0–4 scale) was determined for lung cancer patients. Results: Prevalence of poor PS among lung cancer patients was 34% when estimated by providers and 48% when estimated by patients themselves. Agreement between providers and patients was only fair (weighted [kappa] = 0.41). For both advanced and early stage disease, lung cancer patients were at the highest risk for poor PS compared with other common cancers. Conclusions: The prevalence of poor PS is quite high in lung cancer patients. Providers tend to underestimate poor PS. Specific clinical trials and treatment guidelines for this patient population are urgently needed.

Phase II trial of weekly docetaxel in second‐line therapy for nonsmall cell lung carcinoma

The authors conducted a Phase II study to evaluate the activity and toxicity of weekly docetaxel in second‐line therapy for nonsmall cell lung carcinoma (NSCLC).

Small Cell Lung Cancer: Past, Present, and Future

Small cell lung cancer (SCLC) accounts for about 10% to 15% of all lung cancers. It is characterized by its rapid doubling time, high rate of dissemination, and increased sensitivity to chemotherapy and radiation. Although the incidence of SCLC has been steadily decreasing over time, it remains a serious public health problem given its aggressive clinical behavior and the lack of effective therapies. This review looks at the evolution of SCLC treatment and the standard treatments that are currently available, including platinum-based combination chemotherapy, hyperfractionated thoracic radiation, and prophylactic cranial irradiation. The development of novel therapies for SCLC has been lagging behind, but completed clinical trials and ongoing investigations are helping us define what will be the best therapeutic targets for this disease.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials.

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival times were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0–2 risk factors had similar outcomes independent of treatment, whereas patients with 3–4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy.

Summary statement: Novel agents in the treatment of lung cancer: Advances in epidermal growth factor receptor-targeted agents

The Third Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was convened in Cambridge, Massachusetts on September 23 to 24, 2005 to discuss ongoing research into the significance of the epidermal growth factor receptor (EGFR) pathway in the biology of non–small cell lung cancer

Chemotherapy in Patients ≥80 with Advanced Non-small Cell Lung Cancer: Combined Results from SWOG 0027 and LUN 6

Introduction: We report outcomes for the combined cohort of patients ages 80 or older from two chemotherapy trials in advanced non-small cell lung cancer (NSCLC) conducted by the Southwest Oncology Group (S0027) and an investigator-initiated trial (LUN 6). Methods: Patients with chemotherapy-naïve, stage IIIB/IV NSCLC, ages 70 years or older with a performance status (PS) of 0 or 1, or patients of any age with PS 2, were eligible. Treatment in the S0027 study was 25 mg/m2 of vinorelbine on days 1 and 8, every 21 days for three cycles, and then 35 mg/m2 of docetaxel on days 1, 8, and 15, every 28 days for three cycles. Treatment in the LUN 6 study was 30 mg/m2 of docetaxel on days 1, 8, and 15, every 28 days, or 75 mg/m2 every 21 days. Of the 228 patients treated, 49 (21.5%; 26 in LUN 6 and 23 in S0027) were ages 80 years or older. Analysis of outcome was conducted in the 80-and-older group and was compared with the under-80 cohort from S0027. Results: Among patients with measurable disease, disease-control rates (partial response + stable disease) were 54% (n = 48) and 46% (n = 89) in the 80-and-older and under-80 groups, respectively. Median survival was 7 and 11 months in PS 0/1 patients in the 80-and-older and under-80 groups, respectively. Median survival was 4 and 5 months in PS 2 patients in the 80-and-older and under-80 groups, respectively. Treatment was well tolerated. Five treatment-related deaths were noted: two (4%) and three (3.4%) in the 80-or-younger and the under-80 groups, respectively. Conclusions: These chemotherapy regimens were associated with an encouraging disease-control rate (54%) in patients 80 years or older with advanced NSCLC, with good tolerance. Selected octogenarians with advanced NSCLC may benefit from single-agent chemotherapy.

A Randomized Phase II Trial of Two Schedules of Docetaxel in Elderly or Poor Performance Status Patients with Advanced Non-small Cell Lung Cancer

Background: We conducted a multicenter randomized phase II trial to evaluate two schedules of single-agent docetaxel in the first-line treatment of elderly and performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients 70 years of age and older with a PS 0–1 or patients of any age and PS 2 were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks or 30 mg/m2 on days 1, 8, and 15 every 28 days. The primary end point was frequency of grade 3/4 toxicities. Health-related quality of life, response, and survival were secondary end points. Results: Fifty-five patients were randomized to received docetaxel every 3 weeks and 56 to receive docetaxel weekly. Hematologic toxicity, primarily grade 3/4 neutropenia, was significantly lower in the weekly schedule (0% versus 44%; p < 0.001). Health-related quality of life was similar between the two arms. Efficacy parameters were not significantly different, with a trend toward better survival in the weekly schedule group (6.7 versus 3.5 months). Patients with PS 0–1 had a significantly longer survival compared with PS 2 patients (7.8 versus 2.9 months; p < 0.001). A subset analysis of 30 octogenarian patients revealed similar outcomes as in 70- to 79-year-old patients. Conclusion: Weekly docetaxel is associated with less neutropenia and a trend toward improved survival in elderly or PS 2 patients. PS rather than age is the primary determinant of outcome in this population. Octogenarians benefited from weekly docetaxel. Future studies should separate elderly patients from PS 2 patients.

The evolving role of cetuximab in non-small cell lung cancer

Cetuximab is a monoclonal antibody directed against the ligand binding site in the extracellular domain of the epidermal growth factor receptor (EGFR). Cetuximab is currently approved for the treatment of patients with refractory colorectal cancer. In locally advanced head and neck carcinoma, cetuximab in combination with radiotherapy significantly improved survival compared with radiotherapy alone, and this treatment awaits Food and Drug Administration approval. In previously treated non–small cell lung cancer, single-agent cetuximab produced an objective response in 3 of 66 eligible patients and a median survival of 8.1 months. Treatment was well tolerated, with skin rash as the principal toxicity. The vast majority of patients (60 of 66) expressed EGFR by immunohistochemistry but no correlation existed between response and EGFR mutations. Two single-arm phase II trials testing cetuximab in combination with a platinum-based doublet in previously untreated patients showed responses in the range of 26% to 29%, with median survival times of 10 to 11 months. A European phase II randomized trial tested cisplatin/vinorelbine with or without cetuximab as first-line therapy in 86 patients with advanced non–small-cell lung cancer. Overall efficacy was slightly superior in the cetuximab arm and a phase III trial is currently ongoing to definitively determine the role of cetuximab in this setting.

Efficacy and Safety of Oxaliplatin and Gemcitabine with Bevacizumab in Advanced Non-small Cell Lung Cancer

Introduction: We conducted a multicenter phase II study to evaluate the efficacy and safety of oxaliplatin and gemcitabine with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with chemotherapy-naive, nonsquamous, stage IIIB or IV NSCLC received gemcitabine 1000 mg/m2 on days 1 and 8, oxaliplatin 130 mg/m2 on day 1, and bevacizumab 15 mg/kg on day 1 every 21 days for 4 cycles. Patients with stable disease or response received maintenance bevacizumab every 3 weeks until progression. Primary end point was median time to progression (TTP). Results: Nineteen of 44 eligible patients had partial response in the intent-to-treat analysis for an objective response rate of 43% (95% confidence interval [CI], 26.3–60.1%); 16 patients had stable disease for a disease control rate of 80% (95% CI, 72.0–87.0%). Median TTP was 5.5 months (95% CI, 3.8–6.9 months), which approached that seen in phase III studies. Median survival was 13.7 months (95% CI, 7.3–21.8 months). The most common grade 3 or 4 adverse events were hypertension (11%), neutropenia (9%), diarrhea (7%), dyspnea (7%), and thromboembolic events (7%). Pulmonary hemorrhage was not observed. Conclusions: The results of this phase II study suggest that oxaliplatin and gemcitabine with bevacizumab was active and reasonably well tolerated. Median TTP approached that in phase III studies. This combination represents another treatment option for advanced NSCLC.