Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib.

INTRODUCTION: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. MATERIALS AND METHODS: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. RESULTS: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively. CONCLUSION: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.

Phase I trial of bi-weekly paclitaxel and gemcitabine as second-line therapy for patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

A phase I study was conducted to evaluate the maximum tolerated dose, feasibility, and efficacy of bi-weekly-administered paclitaxel and gemcitabine in patients with non-small-cell lung cancer (NSCLC) who had previously been treated with platinum-based chemotherapy. In a dose-escalation study, 18 patients, under 75 yr old, with unresectable NSCLC that had relapsed or was resistant after platinum-containing chemotherapy with performance status of 0-2 were enrolled. Patients were treated with paclitaxel and gemcitabine bi-weekly. The dose escalation levels of paclitaxel (mg/m2) at a fixed dose of gemcitabine 1000 mg/m2 were 110 (level 1), 130 (level 2), 150 (level 3), and 170 (level 4), respectively. All patients were eligible for evaluation of toxicities. At level 4, one patient developed an infection with grade 3 neutropenia and two other patients developed severe neurotoxicity (over grade 3). Thus, the recommended dose for phase II was paclitaxel 150 mg/m2 and gemcitabine 1000 mg/m2 due to dose-limiting toxicities including neutropenia and peripheral neurotoxicity. Partial response was seen in 4 cases of the 18 assessable patients, with an overall response of 22%. Bi-weekly paclitaxel and gemcitabine is feasible and appears to be an efficacious combination chemotherapy as second-line chemotherapy in refractory and recurrent patients with NSCLC who had been previously exposed to platinum-containing chemotherapy.

Phase II study of weekly docetaxel combined with cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A group of 38 patients with advanced or metastatic NSCLC who had not received prior treatment and who were aged under 75 years were enrolled. The patients received intravenous infusions of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (80 mg/m2, day 1), followed by a week of rest. RESULTS: Six patients had grade 3/4 neutropenia (18%), but there were no episodes of neutropenic fever. Nonhematologic toxicities were also mild. There were 12 partial responses for an objective response rate of 31.6%. The median survival was 11.8 months, and the 1-year survival rate was 46.5%. CONCLUSION: Cisplatin combined with weekly administration of docetaxel is efficacious against NSCLC with low hematotoxicity, and this schedule may be an alternative for the treatment of NSCLC.

[Antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated in major hospitals in Nagano Prefecture].

We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 108 strains of Streptococcus pneumoniae and 144 strains of Haemophilus influenzae isolated from respiratory organs in the First Department of Internal Medicine, Shinshu University, and affiliated hospitals between January 2000 and February 2001. The following results were obtained. 1. Fifty-one (47.2%), 56 (51.9%), and 1 (0.9%) of 108 strains of S. pneumoniae were classified as penicillin-susceptible S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP), respectively. 2. Three carbapenems had potent antimicrobial activity against PISP and PRSP. Furthermore, none of the strains were highly resistant (MIC > 2 micrograms/ml) to benzylpenicillin, ampicillin (ABPC), sulbactam/ampicillin (SBT/ABPC), cefotaxime (CTX), or cefepime (CFPM). 3. Eleven (7.6%) and 6 (4.2%) of 144 strains of H. influenzae were classified as beta-lactamase-producing ABPC-resistant strains and beta-lactamase negative ABPC-resistant H. influenzae (BLNAR), respectively. Levofloxacin, sulfamethoxazole/trimethoprim, and meropenem had potent antimicrobial activity against these resistant strains. 4. BLNAR strains were more highly resistant to CTX, CFPM, SBT/ABPC, and cefaclor than beta-lactamaseproducing strains. 5. In our surveillance study regarding clinical isolates of S. pneumoniae and H. influenzae from respiratory organs in Nagano prefecture, there were regional differences in the isolation rate and antimicrobial susceptibility. The isolation rates of resistant strains were lower than those reported in a nationwide survey.