Results of a phase II trial of gemcitabine in patients with non-small-cell lung cancer and a performance status of 2.

This trial was designed to determine the 1-year survival rate, efficacy, progression-free survival (PFS), and toxicity with gemcitabine in patients with stage IIIB (with pleural effusion) or stage IV non-small-cell lung cancer (NSCLC) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. Gemcitabine 1250 mg/m2 was administered intravenously on days 1 and 8 of each 21-day cycle. Treatment consisted of 6 cycles; patients who responded with complete response or partial response received < or = 2 additional cycles. Forty-two patients were enrolled at 31 community-based centers between March and November 2002. Most patients had stage IV disease (74%). The median age was 73 years (range, 58-84 years), and 19% had received prior palliative radiation therapy. Patients received a median of 3 cycles (range, 1-8 cycles). The median survival was 4.8 months (range, < 1 to 19.2 months), and the estimated 1-year survival was 20%. Median PFS was 2.5 months (range, < 1 to 19.2 months), and PFS at 1 year was 11.1%. Thirty-one patients died of disease progression, and 1 each died of myocardial infarction, brain herniation, pneumonia, and respiratory failure. Seven patients were not evaluable for response; 4 refused or received no treatment, treatment in 2 failed (myocardial infarction and pneumonia), and 1 was lost to follow-up. Among 35 evaluable patients, there were 5 partial responses (14%), 10 with stable disease (29%), and 20 with disease progression (57%). Drug-related grade > or = 3 toxicities included neutropenia (18%), anemia (8%), and dyspnea (2.6%). These results suggest that patients with NSCLC with an ECOG PS of 2 may benefit from single-agent chemotherapy gemcitabine. General toxicity, including myelotoxicity, was relatively low. Further studies comparing single-agent chemotherapy with combination chemotherapy for patients with a PS of 2 are warranted.

Topoisomerase I-based nonplatinum combinations in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-related death in males and females in the United States. Most patients have advanced disease at diagnosis. Chemotherapy is the treatment of choice for patients with good performance status. Progress in the management ofpatients with advanced disease has been slow, and platinum-based combinations result in a small survival benefit. The topoisomerase I inhibitors are active as single agents and in combination with platinums in non-small-cell lung cancer. Nonplatinum-based doublet combinations are beginning to be explored in an attempt to reduce toxicity and improve efficacy. Data available on some of the nonplatinum doublets that include topoisomerase I inhibitors suggest that these regimens provide efficacy equal to that achieved with platinum-based doublets. This article reviews the topoisomerase I-inhibitor nonplatinum combinations in the management of advanced non-small-cell lung cancer.