Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small cell lung cancer requires aggressive combination chemotherapy. The three active agents, doxorubicin (A) 45 mg/m2 i.v. day 1, cyclophosphamide (C) 1.0 mg/m2 i.v. day 1 and VP16-213 (E) 50 mg/m2/day i.v. days 1-5 were given together. The combination (ACE) was given every 21 days without chest irradiation. One hundred and seventy-four patients have been stratified for extent of disease and randomized on three sequential studies testing ACE vs ACE + MER immunotherapy (38 patients), or ACE vs ACE alternating with CCNU, methotrexate, vincristine and procarbazine (109 patients), or ACE vs ACE II (ACE with continuous VP16-213 - 100 mg/m2/day X 5 days - 27 patients - ongoing). The immunotherapy and the alternating non-cross resistant combination have not proven beneficial with respect to response or survival. The ACE combination, regardless of additional treatments, has produced greater than 90% response overall. In limited disease the complete response (CR) frequency is 65%. The median survival for limited disease overall is 14 months and 18 months for patients achieving CR. In extensive disease the CR frequency is 40% with a median survival of 9 months overall and 13 months for patients achieving CR. Response frequency and survival are identical in the first two studies and 20-30% of patients with limited disease are long-term survivors with one late relapse (greater than 3 years). Patients who achieved CR had a significantly longer survival regardless of other factors such as performance status or extent of disease. Prophylactic cranial irradiation was demonstrated to be useful in prevention or delaying CNS metastases in patients who achieved CR. The third generation study of high-dose VP16-213 infusion seeks to increase the CR frequency. ACE chemotherapy without chest irradiation is a highly effective treatment for all patients with small cell lung cancer and compares favorably with all other studies with or without adjuvant radiotherapy.
 ...
PMID:Doxorubicin, Cyclophosphamide and VP16-213 (ACE) in the treatment of small cell lung cancer. 628 82

The records of 227 patients with small cell lung cancer (SMCLC) treated between January 1974 and July 1978 in a series of randomized trials were reviewed to determine the influence of central nervous system (CNS) metastases on survival. Sixteen patients were excluded because of single agent chemotherapy (11), lack of CNS irradiation despite proven metastases (2), prior chemotherapy (2), and concomitant metastatic second primary (1). Of 211 evaluable patients, 100 presented with limited disease and 111 with extensive disease, 25 of whom had CNS metastases at presentation, 21 ("CNS-limited") as the only site of metastases. Treatment of limited patients consisted of chemotherapy and thoracic radiation, while chemotherapy alone was used for extensive patients. No prophylactic brain irradiation was used, but CNS radiation was given to almost all patients when CNS metastases developed. Median survivals were: limited, 13.8 months; CNS-limited, 15.1 months; and extensive 8.6 months (P less than 0.0001). There was no significant difference in the survival experience of limited and CNS-limited patients, although none of the CNS-limited patients experienced long-term remissions. Thirty-five of the limited patients and 21 of the extensive patients subsequently developed CNS metastases. Their median survivals following CNS metastases were 3.7 months and 1.6 months, respectively. In conclusion, CNS metastases as the sole site of metastatic disease at diagnosis of SMCLC is not necessarily a bad prognostic sign, while the subsequent development of CNS metastases may be.
 ...
PMID:The effect of CNS metastases on the survival of patients with small cell cancer of the lung. 629 19

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.
 ...
PMID:Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration. 632 90

Small cell lung cancer (SCLC) is a systemic disease that usually presents with locally bulky disease in the lung and mediastinal nodes, with either subclinical (limited stage) or detectable (extensive stage) extrathoracic metastases. Treatment with local modalities alone leads almost invariably to systemic relapse, and treatment with only systemic therapy usually results in recurrence at sites of initially demonstrated disease. Although prophylactic cranial radiation is far from an ideal solution to the problem of CNS metastases in patients with SCLC, it presently seems preferable to the alternative of observation and generally ineffective palliative treatment at time of relapse in the CNS.
 ...
PMID:Prophylactic cranial irradiation for patients with small cell lung cancer. An enduring controversy. 900 62

Recent progress in the treatment of small cell lung cancer (SCLC) is described in this review article. Many anti-cancer agents have appeared to be active against SCLC. Cyclophosphamide, Adriamycin and vincristine (CAV), cyclophosphamide. Adriamycin and etoposide (CAE), CAV plus etoposide (CAVE), and cisplatin and etoposide (PE) are widely used as the first line chemotherapy. CAV alternating with PE have been considered to be one of the standard regimens in the treatment of SCLC. Dose intensive weekly chemotherapies have suggested to have high response rate and prolong survival in non-randomized trials. However, recent randomized trials have not shown that weekly chemotherapy is superior to 3 weekly chemotherapy. A meta-analysis appears that combined modality of chemotherapy and thoracic radiotherapy (TRT) is superior to chemotherapy alone in the treatment of limited disease (LD) SCLC. Recent clinical trials have demonstrated that concurrent use of PE chemotherapy and twice daily TRT provide survival benefit in the patients with LD-SCLC. Many randomized trials have shown that prophylactic cranial irradiation reduces the incidence of CNS metastases, however, do not prolong the survival of patients with SCLC. Further investigations of new drug and new modality in the treatment of SCLC are warranted.
 ...
PMID:[Therapeutic strategy for small cell lung cancer]. 904 18

We examined the significance of histologic subtyping of small cell lung cancer (SCLC) as a prognostic factor for neurologic complications and in particular central nervous system (CNS) metastases. Pretreatment material of 239 consecutive patients with SCLC was retrospectively reexamined according to the histologic subclassification of the Pathology Panel of the International Association for the Study of Lung Cancer. Besides the classic small cell type (n=178), this subclassification distinguishes two variant cell types: mixed (n=31) and combined (n=1), which were treated as one group in the further statistical analysis. Twenty nine cases were not classified, for the following reasons: autopsy material only (n=14), slides missing (n=7), and initial SCLC diagnosis changed (n=8). The results showed that neurologic complications registered in a prospective neurologic follow-up were common in both subtypes and predominantly metastatic in nature. The data did not reveal any significant difference between histologic subtypes with regard to CNS metastases and brain metastatic-free survival. Paraneoplastic syndromes tended to occur more frequently in patients with classic small cell type. However, this relationship needs further study. It was concluded that no prognostic relevance exists for histologic subtyping with respect to neurologic complications.
 ...
PMID:The role of histopathologic subtyping in predicting neurologic complications in small-cell lung-cancer. 2156 13

The incidence of brain metastases is projected to rise because survival rates of lung cancer, breast cancer, and melanoma continue to improve (1). The brain is being identified as a sanctuary site for harboring metastases despite excellent control of extracranial disease. This is thought to occur because the drug therapies that control extracranial disease have limited central nervous system (CNS) penetration. The development of brain metastases is a devastating diagnosis affecting both quality of life (QOL) and survival. Symptoms after diagnosis can include headache, nausea, vomiting, seizure, neurocognitive decline, and focal neurologic deficit. Some of these symptoms can be irreversible even after successful treatment of intracranial disease. Treatment of brain metastases often necessitates surgery and radiation. There have been some reports of systemic therapies offering an intracranial response however long-term data is lacking. These treatments for CNS metastases can also lead to neurocognitive sequelae impacting quality of life. Therefore, preventing disease from spreading to the brain is a topic that has generated much interest in oncology. Prophylactic cranial Irradiation (PCI) has been used in leukemia, small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). While showing effectiveness in preventing intracranial disease development, its carries with it side effects of neurocognitive decline that can affect QOL. There are Clinical trials exploring novel delivery of PCI and concurrent neuroprotective drug therapy to try to mitigate these neurocognitive sequelae. These will be important trials to complete, as PCI has shown promise in controlling disease and prolonging survival in select patient populations. There are also drug therapies that have shown efficacy in preventing CNS metastases development. This review will explore the current therapies available to prevent CNS metastases.
 ...
PMID:Prevention of Brain Metastases. 3032 85


<< Previous 1 2