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1.
Lung Cancer ; 56(3): 377-81, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17328989

ABSTRACT

BACKGROUND: Extensive-stage small cell lung cancer (SCLC) is a highly aggressive malignancy for which little therapeutic progress has been made over the past 20 years. SCLC is a highly angiogenic tumor and targeting angiogenesis is being investigated. The putative mechanism of action of thalidomide is through inhibition of new blood vessel formation. This trial was designed to evaluate thalidomide in ES-SCLC. PATIENTS AND METHODS: Patients who had received first-line chemotherapy without disease progression were eligible. Patients received thalidomide 200 mg daily as maintenance therapy starting 3-6 weeks after completion of chemotherapy. RESULTS: Thirty patients were enrolled. Toxicity was minimal with grade 1 neuropathy in 27% of patients and only one case of grade 3 neuropathy. Median survival from time of initiation of induction chemotherapy was 12.8 months (95% CI: 10.1-15.8 months) and 1-year survival of 51.7% (95% CI: 32.5-67.9%). Median duration on thalidomide was 79 days. CONCLUSION: Thalidomide 200mg daily is well tolerated when given as maintenance therapy for ES-SCLC after induction chemotherapy. Further evaluation of anti-angiogenic agents in SCLC is warranted.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Thalidomide/administration & dosage , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Michigan/epidemiology , Middle Aged , Neoplasm Staging , Ohio/epidemiology , Retrospective Studies , Severity of Illness Index , Survival Rate , Time Factors , Treatment Outcome
2.
Lung Cancer ; 55(3): 349-55, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17161498

ABSTRACT

BACKGROUND: Total EGFR expression by immunohistochemistry (IHC) has failed to demonstrate prognostic importance. We hypothesized that activation (phosphorylated) state of EGFR (p-EGFR) and its activated downstream signal pathway (p-STAT-3) will have prognostic value in NSCLC. METHODS: 145 patients underwent lung resection for NSCLC at University Hospitals from 1998-2002. A database with TNM stage, gender, age, time to recurrence, and survival was established. p-EGFR and p-STAT-3 levels were quantified by IHC. Specimens were divided into negative, 1+, 2+, or 3+ (5-19%, 20-50%, >50% of tumor cells staining respectively). Cox proportional hazard model was used for multivariate analysis. RESULTS: Median age was 70 years. 58% were female and 54% had adenocarcinoma. Pathologic stage was as follows: stage I: 54%, stage II: 31%, stage III: 15%. 32% were positive for p-EGFR (squamous 36%, adenocarcinoma 29%). p-STAT-3 staining was seen in 38% and was higher in adenocarcinoma (46%) versus squamous cell (27%, p=0.02) and was higher in patients >70 years than compared to those <70 years (p=0.06). There was a trend toward co-expression of p-EGFR and p-STAT-3 (p=0.09). The 5-year Kaplan-Meier probabilities of overall survival were not different amongst patients with activated versus no activation of EGFR and STAT-3. CONCLUSIONS: Although EGFR is commonly expressed in NSCLC ( approximately 70%), p-EGFR is seen in only 1/3 of patients. p-EGFR and p-STAT-3 were commonly co-expressed in tumors compatible with known signal transduction pathways in lung cancer. However, EGFR and STAT-3 activation status does not provide prognostic information in resected disease.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , ErbB Receptors/metabolism , Lung Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Phosphorylation , Prognosis , Signal Transduction/physiology
3.
Invest New Drugs ; 23(6): 563-7, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16034518

ABSTRACT

Rebeccamcyin analogue (RA) is an antitumor antibiotic that results in DNA intercalation and topoisomerase I and II inhibition. Phase I trials of the daily x 5 schedule and once every 3 week schedule have been completed. Antitumor activity was observed during the phase I trials. The purpose of this study is to primarily determine the response rate of 2 different schedules of administration of RA in patients with advanced non-small cell lung cancer (NSCLC) who had progressed on one prior chemotherapy regimen. Secondary endpoints were median and 1-year survival rates. A two-stage Simon design was employed for both arms of the study. Patients were randomly assigned to either of two RA treatment schedules of 500 mg/m(2) as a 1 hr infusion repeated every 3 weeks (Arm A) or 140 mg/m(2)/day x 5 days repeated every 3 weeks (Arm B). Forty-two patients were randomized. No confirmed objective responses were seen. Stable disease was seen in 52% of patients on arm A and 37% on arm B. Median survival and 1 year survival rates were 5.6 months and 33.3% for arm A, 9.7 months and 42.1% for arm B respectively. Cox regression model demonstrated increased risk of death in patients younger than the age of 61 and for patients treated on arm A. RA failed to demonstrate a significant response rate in this disease setting, although the proportion of patients with stable disease and 1-year survival were encouraging and similar to other published studies of approved single agents for second-line therapy of NSCLC.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carbazoles/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Indoles/administration & dosage , Lung Neoplasms/drug therapy , Adult , Aged , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Carbazoles/adverse effects , Carbazoles/therapeutic use , Drug Administration Schedule , Female , Humans , Indoles/adverse effects , Indoles/therapeutic use , Male , Middle Aged , Survival Analysis
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