Patricia Ostler

Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer

PURPOSE This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were treated with erlotinib and evaluated to determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement. PATIENTS AND METHODS Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS. RESULTS Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival. CONCLUSION Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.

Phase II study: integrated palliative care in newly diagnosed advanced non-small-cell lung cancer patients.

PURPOSE To assess the feasibility of early palliative care in the ambulatory setting in patients with newly diagnosed advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients were eligible if they had a performance status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC. Participants received integrated care from oncology and palliative care throughout the course of their disease. Participants were scheduled to meet with the palliative care team (PCT) and complete quality-of-life (QOL) and mood questionnaires monthly for 6 months. The study was deemed feasible if 64% of patients completed at least 50% of their scheduled visits and QOL assessments. RESULTS Fifty-one patients were enrolled onto the trial. One died within 72 hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study participants complied with at least 50% of the palliative care visits. Eight-six percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility requirements by both meeting with the PCT and completing QOL assessments at least 50% of the time. QOL and mood analyses confirmed the high symptom burden in patients with newly diagnosed advanced NSCLC. At least 50% of participants experienced some degree of shortness of breath, cough, difficulty breathing, appetite loss, weight loss, or unclear thinking at their baseline assessment. More than one third of patients had a probable mood disorder at baseline. CONCLUSION Integrated palliative and oncology care is feasible in ambulatory patients with advanced NSCLC.

Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma

We conducted a phase 2, multicenter, open‐label study of erlotinib plus bevacizumab in patients with malignant pleural mesothelioma who had previously received 1 prior chemotherapy regimen. These agents have activity in non–small cell lung cancer, but their role in mesothelioma is unclear. The primary endpoint is response rate. Secondary endpoints include time to progression, survival, and toxicity.

Aggressiveness of care in a prospective cohort of patients with advanced NSCLC.

Optimal end of life care of patients with terminal cancer is poorly understood. In this study, the aggressiveness of care is described in a cohort of patients with newly diagnosed advanced nonsmall‐cell lung cancer (NSCLC).

Preliminary results from a phase II study of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in patients > 70 years of age with previously untreated advanced non-small cell lung carcinoma

7080 Background: Chemotherapy for patients ≥ 70 years of age with advanced NSCLC can be associated with greater toxicities than in younger patients. The identification of an efficacious therapy with minimal systemic toxicity would be particularly beneficial to elderly subjects. Erlotinib (Tarceva™) has shown promising activity, and a tolerable side effect profile, in the treatment of patients who have failed prior chemotherapy. We thus chose to conduct a single center phase II trial of erlotinib in patients ≥ 70 with previously untreated advanced NSCLC. METHODS Patients: chemotherapy naïve, IIIB (w/malignant effusion)/IV, PS 0-2; treated with erlotinib, 150 mg p.o. q.d., until evidence of disease progression or toxicity. Primary endpoint: median survival; secondary endpoints: response rate, quality of life (using LCSS), changes in FDG-PET, and analysis of EGFR signaling pathway from pre-treatment tumor specimens. RESULTS From 3/03 to 12/03, 36 pts were treated; 30 evaluable for toxicity and response; 1 for toxicity only; 5 too early. M/F: 19/17; median age 76 (70-86); PS 0/1/2:6/28/2; Path: adeno, 56%; squamous 14%; adeno w/BAC features, 11%; BAC, 11%; NSCLC unclassified 11%, large cell, 2%. Smoking: current/former/never: 2/30/4. TOXICITY rash 77%(grade 1/2: 92%, grade 3: 8%, grade 4:0%), diarrhea 61% (grade 1/2: 100%, grade3/4:0%). Other ≥ grade 3 toxicities: pneumonitis 2/31 (6.5%) and lacrimation 1/31 (3.2%). One patient died from drug toxicity (pneumonitis); 3/31 (9.6%) were dose reduced; 2/31 (6.5%) discontinued. RESPONSE CR:0; PR: 4 (13.3%; 95% CI 5 - 29%); SD: 14 (46.6%; 95% CI 31-64%); PD:12 (40%). Median duration of response and stable disease: 6.8 (range 3.5-7.5+) and 3.5 months (range 1.5-8.0+), respectively. Survival and FDG-PET imaging are too early to evaluate. CONCLUSIONS Erlotinib appears to be well tolerated and demonstrates encouraging activity in patients ≥ 70 years of age with previously untreated advanced NSCLC. Accrual is continuing to 60 patients and updated response, survival and FDG-PET data will be presented. [Table: see text].

Brief Report of Biweekly Pemetrexed and Gemcitabine in Elderly Patients with Non-small Cell Lung Cancer

We examined a nonplatinum-based doublet chemotherapy regimen, pemetrexed and gemcitabine given on a biweekly (every 14 days) schedule, in patients older than 70 years with newly diagnosed advanced non-small cell lung cancer. The study was closed after nine patients were treated due to excess toxicity, primarily fatigue, and nonneutropenic infection. No responses were observed. Eight of the nine patients were hospitalized during therapy and seven discontinued treatment for reasons other than progressive disease. Median progression-free survival was 1.7 months, and median overall survival was 3.9 months. We found that biweekly pemetrexed and gemcitabine was too toxic in our cohort of elderly patients with newly diagnosed advanced non-small cell lung cancer.