Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

OBJECTIVE: The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. METHODS: Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. RESULTS: A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). CONCLUSIONS: The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Feasibility re-evaluation of 75 mg/m² docetaxel in Japanese patients with previously treated non-small cell lung cancer.

OBJECTIVE: The primary objective of this study was to re-evaluate the feasibility of docetaxel at doses of up to 75 mg/m² in Japanese patients with previously treated non-small cell lung cancer. METHODS: Patients received escalated doses of docetaxel at 70 mg/m² (level 1) or 75 mg/m² (level 2) every 3 weeks until disease progression or unacceptable toxicities. Dose escalation was decided on the basis of dose-limiting toxicity in the first cycle of chemotherapy. RESULTS: At dose level 1, dose-limiting toxicity--Grade 3 febrile neutropenia--was observed in one of the six patients and at dose level 2, it was seen in one of the first six patients. Therefore, an additional 14 patients were enrolled at dose level 2, as originally planned. Among the total of 20 patients at dose level 2, 6 (<33%) developed dose-limiting toxicity in the first cycle: febrile neutropenia in 5 and pneumonia in 1. Finally, 10 (50%) of the 20 patients experienced toxicities that met the dose-limiting toxicity criteria, including 8 with febrile neutropenia throughout the treatment period, but this was manageable with dose reduction or appropriate supportive care. Other observed toxicities were predictable from the safety profile of decetaxel and were also well managed. Four partial responses were observed, giving an overall response rate of 15.4%. The median progression-free survival period of the patients overall was 4.0 months (95% confidence interval 1.4-6.6 months). CONCLUSIONS: Although docetaxel administration at an initial dose of 75 mg/m² requires careful attention because of the high incidence of febrile neutropenia, this dose is considered feasible according to the protocol definition in Japanese patients with previously treated non-small cell lung cancer.

Prognostic value of EGFR mutation and ERCC1 in patients with non-small cell lung cancer undergoing platinum-based chemotherapy.

BACKGROUND: In order to improve the outcome of patients with non-small cell lung cancer (NSCLC), a biomarker that can predict the efficacy of chemotherapy is needed. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC. METHODS: We conducted a retrospective study to analyze the relationships between EGFR mutations or ERCC1 expression and progression-free survival (PFS) in patients with NSCLC who received platinum-based chemotherapy. EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and immunohistochemistry was used to examine the expression of ERCC1 in tumor samples obtained from the patients. RESULTS: Among the NSCLC patients who received platinum-based chemotherapy, the median PFS was significantly better in those who had never smoked and those with exon 19 deletion, and the median overall survival (OS) was significantly better in those who had never smoked, those with exon 19 deletion, and women. Cox regression analysis revealed that exon 19 deletion and having never smoked were significantly associated with both PFS and OS. Subset analysis revealed a significant correlation between ERCC1 expression and EGFR mutation, and ERCC1-negative patients with exon 19 deletion had a longer PFS than the other patients; ERCC1-positive patients without exon 19 deletion had a shorter PFS than the other patients. CONCLUSIONS: Our results indicate that among NSCLC patients receiving platinum-based chemotherapy, those with exon 19 deletion have a longer PFS and OS. Our findings suggest that platinum-based chemotherapy is more effective against ERCC1-negative and exon 19-positive NSCLC.

Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis.

Previous studies have demonstrated that both gefitinib and erlotinib are markedly effective for the treatment of non-small-cell lung cancer (NSCLC) with somatic activating mutations of the epidermal growth factor receptor gene (EGFR-mt). These agents are considered to act on EGFR through the same mechanism. However, the efficacy of these agents against EGFR wild-type (-wt) NSCLC remains unclear, and the frequency of adverse events (AEs) appears to differ between them at each approved dose. Here, we conducted a retrospective analysis of AEs and drug efficacy in patients with NSCLC whose EGFR mutation status had been confirmed and who all received 250 mg gefitinib or 150 mg erlotinib once daily. The erlotinib group (n = 35) had more AEs, including rash, fatigue, stomatitis, anorexia and constipation. On the other hand, liver dysfunction and nail change were more frequent in the gefitinib group (n = 107). AEs of ≥grade 2, including rash, fatigue and nausea, were more frequent in the erlotinib group. The erlotinib group also showed more of a tendency to require dose reduction due to AEs. With regard to treatment efficacy for patients with EGFR-wt, there was no significant difference in progression-free survival between the two drug groups. However, this study has several limitations as of the nature of retrospective design; our data suggest that gefitinib and erlotinib might have almost equal efficacy for patients with EGFR-wt NSCLC, as is the case for patients with EGFR-mt tumors, although erlotinib appears to have higher toxicity than gefitinib at each approved dose.

Clinical practice in management of hydration for lung cancer patients receiving cisplatin-based chemotherapy in Japan: a questionnaire survey.

A questionnaire survey was performed to investigate the actual hydration methods used with cisplatin-containing regimens at various institutions in Japan to gain an overview of the varieties employed. Replies were received from 368 of 686 institutions board-certified by the Japanese Respiratory Society. In 233 institutions (63%), new lung cancer patients were treated regularly with regimens containing cisplatin at ≥60 mg/m2. In 172 institutions (48%), hydration with <3000 ml of intravenous saline was performed on day 1. In 225 institutions (65%), hydration was performed for up to 3 days at most, but no more than 48 (14%) of the institutions that responded did so on day 1 only. Two to three weeks of hospitalization was needed for the initial course at most institutions (76%). Thirteen institutions (4%) treated patients as outpatients after the second course, whereas none did so from the beginning of treatment. Despite inconsistencies among the methods used by the various institutions, 84% of those surveyed considered their approaches to be appropriate. Some useful objective indices for deciding the volume or duration of hydration are needed.