A phase II study of amrubicin as a third-line or fourth-line chemotherapy for patients with non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0901.

Amrubicin, a third-generation synthetic anthracycline agent, has favorable clinical activity and acceptable toxicity for the treatment of patients with non-small cell lung cancer (NSCLC) and small cell lung cancer. We conducted this study to evaluate the efficacy and safety of amrubicin for advanced NSCLC patients as a third- or fourth-line therapy. Eligible patients had recurrent or refractory advanced NSCLC after second- or third-line therapy. Patients received amrubicin, 35 mg/m(2) i.v. on days 1-3 every 3 weeks. The primary endpoint was the disease control rate (DCR). Secondary endpoints were the overall survival (OS) time, progression-free survival (PFS) time, response rate, and toxicity profile. Of the 41 patients enrolled, 26 received amrubicin as a third-line and 15 received it as a fourth-line therapy. The median number of treatment cycles was two (range, 1-9). Objective responses were complete response (n = 0), partial response (n = 4), stable disease (n = 21), progressive disease (n = 15), and not evaluable (n = 1), resulting in a DCR of 61.0% (95% confidence interval, 46.0%-75.9%). The overall response rate was 9.8% (95% confidence interval, 0.6%-18.8%). The median PFS interval was 3.0 months, median OS time was 12.6 months, and 1-year survival rate was 53.7%. Grade 3 or 4 hematological toxicities were neutropenia (68%), anemia (12%), thrombocytopenia (12%), and febrile neutropenia (17%). Nonhematological toxicities were mild and reversible. No treatment-related deaths were observed. Amrubicin showed significant clinical activity with manageable toxicities as a third- or fourth-line therapy for patients with advanced NSCLC. This study provides relevant data for routine practice and future prospective trials evaluating third- or fourth-line treatment strategies for patients with advanced NSCLC.

A phase II trial of erlotinib monotherapy for pretreated elderly patients with advanced EGFR wild-type non-small cell lung cancer.

BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which is an effective treatment for patients with non-small cell lung cancer (NSCLC), especially those harboring activating EGFR mutations. A previous phase III trial suggested that patients with EGFR wild-type (EGFR-wt) NSCLC or elderly patients with disease progression after cytotoxic chemotherapy might benefit from erlotinib monotherapy. However, few studies have prospectively evaluated the efficacy and safety of second- or third-line erlotinib monotherapy for elderly patients with EGFR-wt advanced or recurrent NSCLC. METHODS: Pretreated patients aged ≥70 years with EGFR-wt stage IIIB/IV NSCLC or those with postoperative recurrence were enrolled and received oral erlotinib at a dose of 150 mg/day until disease progression. Primary outcome was the objective response rate (ORR). Secondary end points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: This study was terminated early because of the results from a Japanese phase III trial (DELTA trial). Sixteen patients were enrolled between April 2010 and May 2013. The median age was 78 years (range 70-84 years). Six patients were female. Five patients had an Eastern Cooperative Oncology Group performance status of 0. Eleven (69%) patients had adenocarcinoma. Fifteen (94%) patients were treated with erlotinib as a second-line therapy. The ORR was 0% [95% confidence interval (CI) 0-17.1]. DCR was 56.3% (95% CI 33.2-76.9). The median PFS and OS were 1.7 months (95% CI 1.3-2.2) and 7.2 months (95% CI 5.6-8.7), respectively. The most commonly occurring adverse events included acneiform eruption (31.3%) and skin rash (25.0%). One patient developed grade 3 interstitial lung disease, which improved following steroid therapy. CONCLUSIONS: In pretreated elderly patients with advanced or recurrent EGFR-wt NSCLC, daily oral erlotinib was well tolerated; however, administration of the drug should not be considered as a second line therapy. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000004561 (Date of registration: November 15th, 2010).

Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902.

PURPOSE: This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed. METHODS: Forty-one patients received CBDCA at a dose targeting an area under the concentration-time curve of 5 mg/mL × min and PEM of 500 mg/m(2) on day 1 every 3 weeks. Single-nucleotide polymorphisms of the thymidylate synthase (TYMS) coding gene, the variable number of tandem repeat (VNTR) in the TYMS, and the methylenetetrahydrofolate reductase (MTHFR) coding gene were analyzed. RESULTS: The overall RR was 36.6 %. Median progression-free survival and median survival time were 4.7 months [95 % confidence interval (CI) 3.9-5.6 months] and 16.2 months (95 % CI 6.1-26.2 months), respectively. Epidermal growth factor receptor gene mutations were detected in 6 patients (14.6 %). The VNTR in the TYMS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038). CONCLUSIONS: This combination therapy was effective and tolerable in patients with advanced non-sq NSCLC. The VNTR in the TYMS appears to be a predictive factor for anemia and thrombocytopenia in patients treated with this regimen.