Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.

PURPOSE: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. EXPERIMENTAL DESIGN: EGFR mutations in exons 18 to 21 were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. RESULTS: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). CONCLUSIONS: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.     

Chemotherapy for non-small cell lung cancer in elderly patients

STUDY OBJECTIVE: To determine the appropriate chemotherapy regimen for inoperable, chemotherapy-na?ve non-small cell lung cancer (NSCLC) in elderly patients. SETTING: National teaching hospital in Taiwan. DESIGN: We retrospectively analyzed data from our clinical trials for a total of 270 patients and compared them with the data from other studies, addressing the elderly in particular or providing subgroup information on age, to analyze the feasibility of current chemotherapy options for elderly patients and possible alternative approaches. RESULTS: The response rates and median survival times of fit elderly patients with NSCLC who were receiving appropriate new anticancer drugs for chemotherapy, including single-agent or combination treatment, were no worse than those of younger patients, and the response rates may have been even higher in the elderly patients, while survival time was slightly poorer in this group. The risk of adverse side effects, such as myelosuppression and peripheral neuropathy, may be higher in elderly patients, who also visit the hospital more frequently. Some items on the lung cancer symptom scale for elderly patients were rated as being slightly worse than those for younger patients after chemotherapy. CONCLUSION: Advanced age alone should not preclude chemotherapy. New single-agent drugs, and non-platinum-based or platinum-based doublets, can all be considered as appropriate treatment for selected fit elderly patients with advanced NSCLC.     

Phase II randomized trial of tri-weekly versus days 1 and 8 weekly docetaxel as a second-line treatment of advanced non-small cell lung cancer

BACKGROUND: For orientals, titrating doses of docetaxel (60-66 mg/m(2)) have shown equal effectiveness and fewer side effects as a second-line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC). Under such doses, there were no comparative data between classic tri-weekly and Days 1 and 8 weekly schedules. METHODS: This Phase II randomized prospective study was designed to compare the toxicity profile, efficacy and quality-of-life (QOL) between these two schedules of docetaxel in the treatment of previously treated patients with advanced NSCLC. Fifty patients were randomized to docetaxel arm A (66 mg/m(2) Day 1) and B (33 mg/m(2) Days 1 and 8) given every 3 weeks. RESULTS: The overall response rates (ORRs) were 12 and 24% in arm A and B, respectively (P = 0.46), and disease control rates were 52 and 48%. The median time-to-progression (TTP) was 11.3 and 12.7 weeks and median survivals were 33.4 and 27.6 weeks, respectively. Both arms have same 1 year (36%) and 2 year survivals (12%). Arm A had significantly higher neutropenia but less compromised QOL. In this study, the response of second-line chemotherapy was significantly better in the group that was response to front-line chemotherapy (P = 0.032). CONCLUSIONS: While Days 1 and 8 weekly docetaxel schedules show higher ORR and less hematological toxicity, there is no advantage to tri-week schedule in terms of TTP and survival, but more compromised QOL.     

Familial sarcoidosis in Taiwan.

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and is uncommon in Taiwan. No cases of familial sarcoidosis have been reported in Taiwan. In this article, we report a mother and son pair who had sarcoidosis. The 56-year-old mother sought medical help for chronic cough for 3 months in 1993. Enlarged mediastinal lymph nodes were demonstrated on chest computed tomography. Besides, two small erythematous papules on her face were observed. Mediastinoscopic biopsy and skin biopsy showed non-caseating granulomatous inflammation. Sarcoidosis was thus diagnosed. The human leukocyte antigen (HLA)-typing of the patient was HLA-A2, A11, B35, B39, CW4, CW7, DR8 and DQ6. Eleven years later, her son was also diagnosed with sarcoidosis proved by mediastinoscopic biopsy. His HLA-typing was HLA-A2, A24, B39, B48, CW7, CW8, DR8 and DQ6. This is the first report of familial sarcoidosis in Chinese people. More cases are needed for further investigation of genetic predisposition among Chinese people.     

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.     

A randomized phase II study of vinorelbine plus gemcitabine with/without cisplatin against inoperable non-small-cell lung cancer previously untreated

Phase II studies have suggested that vinorelbine (V) plus gemcitabine (G) treatment has a similar response rate and better toxicity profile than cisplatin-based combination chemotherapy in non-small-cell lung cancer (NSCLC). Our aim was to evaluate whether or not the addition of cisplatin (P) to a VG regimen increases the efficacy or toxicities in chemo-naive inoperable NSCLC patients. From April 2002 to October 2003, 86 patients were enrolled. The treatment dose was V 20 mg/m2 plus G 800 mg/m2 intravenous infusion (i.v.) on days 1, 8 and 15, with/without P 60 mg/m2 i.v. on day 15, every 4 weeks. The efficacy and toxicity of the treatment were recorded. In all, 125 cycles of VG and 178 cycles of VGP were given to the patients in the VG and VGP arms, respectively (P = 0.001). The median cycle of treatment was three in the VG arm and five in the VGP arm. There were 10 partial responses (overall 23.3%) in the VG arm and 1 complete response and 19 partial responses (overall 46.5%) in the VGP arm (P = 0.022). Neutropenia, nausea, vomiting, and peripheral neuropathy were more common in the VGP arm (P = 0.023, 0.002, 0.025, 0.001, respectively). The Lung Cancer Symptom Scale showed no difference between the VG and VGP arms after two cycles of treatment or when the patient went off study. We concluded that the addition of P to VG treatment did increase both the tumor response rate and the toxicities. However, the toxicities were tolerable.     

Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Gefitinib is active and well tolerated in patients with advanced non-small cell lung cancer (NSCLC); however, its role in patients with brain metastases has not been clearly defined. We had conducted a prospective study to give gefitinib to NSCLC patients irrespective of their performance status (PS), number of prior treatment regimens and the presence of brain metastases. A total of 76 patients were enrolled. Fifty-seven patients had measurable lesions and the objective response rate was 33.3% (95% confidence interval [95% CI], 20.7-46.0%). For all enrolled patients, the disease control rate was 63.2% (95% CI, 52.1-74.3%) with a median progression-free survival of 5.0 months (95% CI, 3.6-6.5 months) and median overall survival 9.9 months (95% CI, 4.9-14.8 months). Twenty-one patients had simultaneously assessable intracranial lesions (ICLs) and extracranial lesions (ECLs), 17 of them (81.0%) showed comparable tumor response. There was no survival difference between the patients with and without metastatic brain disease. Most drug-related adverse events were mild. Intolerable toxicities happened in five patients, four of them were interstitial pneumonia (5.8%). Severity of skin toxicity was tightly associated with tumor response and patient survival (P = 0.007 and <0.001) and the association was consistent in the analysis using early toxicity profile (P = 0.033 and 0.001). In conclusion, gefitinib is active in patients with brain metastasis from NSCLC and tumor response is related to skin toxicity. It is feasible to conduct randomized trials to identify the role of gefitinib alone or in combination with other modality for treatment of NSCLC patients who have metastatic brain lesion(s).