This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were treated with erlotinib and evaluated to ...determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.
Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.
Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.
Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.
Literature on the epidemiology of herpes zoster (HZ) in cancer patients is sparse and does not include the elderly. The objectives of this study were to determine the incidence of HZ and related ...complications in elderly cancer patients and assess risk factors associated with HZ.
Patients ≥65 years diagnosed with cancer in 1991-2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) cancer registry-Medicare linked database in this retrospective, longitudinal, open cohort study. The observation period spanned from first cancer diagnosis until the end of data availability. A random group of non-cancer Medicare patients served as the comparison group. Cases of HZ and related complications were ascertained from medical claims. Incidence rates (IR) and adjusted IR ratios were reported.
The study population consisted of 82,832 hematologic (HEM) and 944,777 solid cancer patients (SOLID). During follow-up, 9.2% of HEM and 6.3% of SOLID were diagnosed with HZ. The IR of HZ was significantly higher in HEM than SOLID (31.0 vs. 14.9 per 1,000 patient-years, p <0.01). The adjusted IR ratio vs. non-cancer elderly patients was 2.4 in HEM and 1.2 in SOLID. The proportion of patients with complications was higher in HEM than SOLID (17.8% vs. 15.8%, p <0.01). Age, gender, race, certain cancer therapies, and immunosuppression were HZ risk factors.
Elderly cancer patients run a 1.2-2.4 times higher risk of developing HZ than those without cancer. The rates of HZ and HZ-related complications are significantly higher for hematologic than solid cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of our study was to report our initial experience with patients who underwent percutaneous imaging-guided radiofrequency ablation of thoracic lesions, and to emphasize technical and ...multidisciplinary issues and adjunctive procedures specific to thoracic tumor ablation.
Our cohort consisted of 30 patients with a spectrum of primary (n=18) and secondary (n=11) lung tumors, mesothelioma (n=1), and five secondarily eroded, painful ribs who underwent ablation of 36 total lesions (one patient had two ablations). Patients either were nonsurgical candidates because of medical comorbidities or extent of disease, or had exhausted chemotherapy and radiation therapy options, or had refused surgery or undergone unsuccessful surgery. Patients were treated with radiofrequency ablation after agreement among oncologists, thoracic surgeons, and interventional radiologists. An array-style electrode under impedance control was used to treat 29 thoracic tumors and the adjacent rib metastases (n=5). A cool-tip radiofrequency probe was used for two patients. CT guidance and general anesthetic were used for all but one patient. Sonographic guidance and IV conscious sedation were used in one patient. Pain (n=11) and tumor cure or control (n=19) were the primary indications for the procedures. Adjunctive procedures to the radiofrequency ablations included the creation of saline or water windows (n=3); establishment of transosseous and transchondral routes (n=4); use of intercostal and paravertebral nerve blocks (n=15); and use of an intraprocedural catheter (n=1), needle (n=1), or sheath (n=3) for treatment of pneumothoraces. Follow-up was from 2 to 26 months.
All ablations were technically successful. No periprocedural mortality occurred. Necrosis of tumor was greater than 90% in 26 of 30 lesions based on short-term follow-up imaging (CT, PET, MRI). In the 11 patients who underwent ablation for pain, relief was complete in four and partial in the other seven. One patient developed a local skin burn, four patients had self-limited hemoptysis up to 4 days after ablation, one had transient atrial fibrillation, one developed hoarseness, and two patients were transiently reintubated after extubation. Eight pneumothoraces developed; one patient underwent placement of a chest tube. Four patients died within 1 year of ablation from extrathoracic spread of tumor.
Radiofrequency ablation for a variety of thoracic tumors can be performed safely and with a high degree of efficacy for pain control and tumor killing. The effect of ablation can be assessed with CT, MRI, or PET. Various technical issues differentiate thoracic tumor ablation from standard abdominal ablations. Numerous other thoracic interventional radiology procedures are beneficial to assist the radiofrequency ablation. A multidisciplinary approach offers valuable expertise for patient care.
Clinical Mimics of Lymphoma Brown, Jennifer R.; Skarin, Arthur T.
The oncologist (Dayton, Ohio),
July 2004, Letnik:
9, Številka:
4
Journal Article
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Odprti dostop
Learning Objectives
After completing this course, the reader will be able to:
Determine when lymphadenopathy is of concern and merits biopsy.
Identify the benign causes of significant ...lymphadenopathy.
Identify the unusual lymphoproliferative disorders that can cause significant lymphadenopathy.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Lymphadenopathy is a common clinical finding and is frequently benign. Warning signs suggestive of a malignant etiology include lymph nodes >2 cm in size, supraclavicular location, and generalized lymphadenopathy associated with hepatosplenomegaly or systemic symptoms. A metastatic solid tumor is always in the differential diagnosis of localized lymphadenopathy, particularly in older individuals. In the case of more generalized lymphadenopathy, in addition to the more common lymphomas, benign etiologies as well as benign and atypical lymphoproliferative disorders need to be considered. Benign etiologies of lymphadenopathy can include infections, autoimmune disorders, drug hypersensitivity reactions, sarcoidosis, and amyloidosis. Rare but benign lymphoproliferative disorders include Kikuchi's disease, Rosai‐Dorfman disease, and progressive transformation of germinal centers. Atypical lymphoproliferative disorders that bear close surveillance for evolution to a more aggressive malignancy include Castleman's disease, lymphomatoid granulomatosis, and lymphomatoid papulosis. Previously considered in this category but now classified as a true lymphoma is angioimmunoblastic lymphadenopathy with dysproteinemia. Physicians need to be aware of all of these disorders when evaluating suspicious lymphadenopathy, while also considering the more common lymphomas and leukemias.
Purpose: To investigate the anti-tumor activity and toxicity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839 or Iressa™; AstraZeneca Pharmaceuticals, Wilmington, DE), in ...patients with advanced non-small cell lung cancer (NSCLC).
Methods: This was an open label, expanded access program (EAP) of oral gefitinib administered at 250
mg per day continuously until evidence of undue toxicity or disease progression.
Results: Two hundred consecutive patients with advanced NSCLC were enrolled in this study. The median number of prior chemotherapy regimens was 2 (range 0–6). One hundred seventy-two patients were treated with gefitinib; 23 expired from disease progression prior to treatment and 5 withdrew their consent. One hundred fifty-four patients are evaluable for toxicity; 8 (5.2%) experienced grade 3/4 toxicity; 2 patients discontinued therapy for grade 3 rash and one for grade 3 nausea. Of 172 patients evaluable for efficacy, 7 (4.1%; 95% CI; 1.7–8.2%) experienced a partial response (PR); 60 patients (34.9%) had stable disease (SD) as their best response. Median survival for all patients was 4.5 months (95% CI; 4.1–4.9 months). One-year survival was 29%. Significant independent prognostic factors associated with improved survival were female gender, good performance status (0/1), and adenocarcinoma histology.
Conclusion: Gefitinib has anti-tumor activity, in a heterogeneous population of NSCLC patients treated on the EAP study. Treatment with gefitinib in this population is associated with a longer survival in women, those with good performance status and in patients with adenocarcinomas. These findings need to be further validated in additional clinical studies.
Small cell lung cancer (SCLC) frequently presents as metastatic disease. It would be useful to detect serum tumor biomarkers at an earlier stage in order to improve the overall survival.
Serum ...samples from SCLC patients (6 limited disease, 7 extensive disease, 4 relapsed disease, 4 no evidence of disease post-treatment) and 5 normal controls were used to identify tumor biomarkers utilizing proteomics. Serum hepatocyte growth factor was also studied using standard ELISA.
Utilizing MALDI-TOF-Mass Spectrometry (MS) based protein identification techniques, a SCLC specific overexpressed protein was identified to be haptoglobin alpha-subunit, with its serum level correlating with the disease stage. The mean level of alpha-haptoglobin was increased in SCLC serum as compared to the normal controls. Serum HGF was also studied as potential tumor biomarker and was found to correlate with the disease status. Either serum alpha-haptoglobin relative level (above 1.9 U), or HGF level (above 500 pg/ml) was associated with a trend towards worse survival.
Our current findings suggest that serum levels of alpha-haptoglobin and HGF may serve as useful serum tumor biomarkers in SCLC. It would now also be useful to determine if these serum biomarkers are altered in response to therapy for this disease.
Purpose: Marimastat is an orally bioavailable inhibitor of matrix metalloproteinases. A phase I study was initiated to determine whether
conventional doses of carboplatin and paclitaxel are tolerated ...when combined with marimastat and to assess the influence of
marimastat on paclitaxel pharmacokinetics.
Experimental Design: Three dose levels were evaluated. Marimastat (10 or 20 mg oral administration b.i.d.) was administered continuously with
paclitaxel (175 or 200 mg/m 2 as a 3-hour i.v. infusion) and carboplatin (at a dose providing an area under the free drug plasma concentration-time curve
of 7 mg min/mL) administered each 3 weeks. Toxicity and response were evaluated throughout the intended four cycles of combined
therapy. The plasma pharmacokinetics of paclitaxel was determined in each patient both without concurrent marimastat and after
receiving marimastat for 1 week.
Results: Twenty-two chemotherapy-naive patients with stage IIIb (27%) or stage IV (73%) non–small cell lung cancer were enrolled.
Their median age was 56 years (range, 39-73 years), 50% were female, and their performance status (Eastern Cooperative Oncology
Group) ranged from 0 to 2. Treatment was well tolerated, as 18 (82%) of the patients completed all four cycles of chemotherapy
without dose-limiting toxicity. Grade 2 musculoskeletal toxicities were reported in 3 of 12 patients receiving marimastat
(20 mg b.i.d.). Nine patients required dose reductions, predominantly related to low-grade myelosuppression. Partial responses
occurred in 12 of 21 (57%) evaluable patients with disease stabilization in another 5 (19%). Marimastat had no effect on paclitaxel
pharmacokinetics.
Conclusions: The administration of marimastat (10 mg b.i.d.) with paclitaxel (200 mg/m 2 ) and carboplatin at an area under the free drug plasma concentration-time curve of 7 mg min/mL was well tolerated with no
apparent pharmacokinetic interaction. Study of this drug combination in the adjuvant setting should be considered if tissue
inhibition of matrix metalloproteinase activity can first be shown.
To review several recently described molecular abnormalities in lung cancer and discuss their potential diagnostic and therapeutic relevance.
Articles were identified through a Medline search (1966 ...to 1997) and studies, including reviews, were cited in the references.
Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A. RAS is a 21-kd G protein and up to 30% of adenocarcinomas show mutations in K-RAS oncogene. MYC encodes a transcriptional activator and amplification may adversely affect survival in small-cell lung cancer (SCLC). The growth factor receptor c-erbB-2 is overexpressed in up to 25% of non-small-cell lung cancer (NSCLC) cases. BCL-2, a negative regulator of apoptosis, is expressed differently in some NSCLCs. Abnormalities of RB, a key regulator of cell cycle, are detected in greater than 90% of SCLCs. There is an inverse relationship in lung cancer cells between expression of RB and p16INK4A, an upstream regulator of RB. Mutations of p53, with frequencies up to 50% in NSCLC and 80% in SCLC, can lead to loss of tumor-suppressor function, cellular proliferation, and inhibition of apoptosis. The identified molecular abnormalities in lung cancer are currently used to develop diagnostics for detecting early disease, as well as to identify targets for gene therapy.
Genetic abnormalities involved in the pathogenesis of lung cancer are rapidly being delineated. Understanding molecular abnormalities in lung cancer could potentially lead to earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.
ABSTRACT
Objectives: With new oral chemotherapy drugs emerging, it is useful to understand the costs associated with traditional intravenous (IV) therapy. This study aims to assess costs associated ...with IV chemotherapy in patients with small cell lung cancer (SCLC) from the perspective of large employer-payers.
Study design: Descriptive retrospective claims database analysis.
Methods: Using medical claims data from 5.5 million beneficiaries between 01/01/1998 and 01/31/2006, we identified patients with lung cancer (ICD-9 codes 162.3-162.9, 176.4, or 197.0) who received IV chemotherapy. A case-finding SCLC algorithm was then applied which selected patients who were treated with chemotherapies commonly used in SCLC (cisplatin/etoposide, cisplatin/irinotecan, carboplatin/etoposide, topotecan, or cyclophosphamide/doxorubicin/vincristine) and then excluded those who had treatments or procedures indicative of non-small cell lung cancer (NSCLC) (positron emission tomography PET scan imaging, lung surgery, common NSCLC chemotherapies). Average total costs paid per day of IV chemotherapy administration were computed, along with separate costs for IV chemotherapy drugs, IV chemotherapy administration procedures, and other drugs and services received on IV visit days. Costs were also estimated per course of treatment based on the assumption of four chemotherapy cycles per course with three visits per cycle.
Results: Among 8010 patients with a lung cancer diagnosis, 802 were identified as SCLC. In the SCLC subset, the average total daily cost was $787 ($9449/course), with $395 ($4742/course; 50.2%) attributable to IV chemotherapy drugs, $93 ($1112/course; 11.8%) to IV chemotherapy administration, and $300 ($3595/course; 38.0%) to other drugs and services.
Conclusions: The proposed algorithm identified about 10% of patients with lung cancer receiving IV chemotherapy as likely SCLC cases. Future studies should validate this algorithm with medical records data. IV chemotherapy administration and other visit-related drugs and services represented about half of the total cost per IV visit day, with the remainder attributable to direct costs for IV chemotherapy drugs.
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