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

The use of chemotherapy for the treatment of brain metastases arising from lung cancer has been limited by poor efficacy and high toxicity. Temozolomide, an orally bioavailable alkylating agent that crosses the blood-brain barrier, has activity against brain metastases from both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) when used as a single agent, but response rates are low. Preclinical experiments and early clinical studies in other malignancies indicate that temozolomide may have additive or synergistic effects when used with other chemotherapeutic agents. We report a case of a patient with SCLC with recurrent brain metastases after treatment with multiple chemotherapeutic regimens and whole-brain radiation therapy (WBRT) who was treated with temozolomide (150 mg/m(2) for 5 days in a 28-day cycle) and oral etoposide (50 mg/m(2) for 10 days in a 28-day cycle). A second patient with NSCLC and brain metastases who progressed after treatment with chemotherapy and WBRT was treated with temozolomide (150 mg/m(2) for 5 days in a 28-day cycle) and gemcitabine (1,000 mg/m(2) weekly for 2 weeks in a 3- week cycle). In both patients, the temozolomide regimens were extremely well tolerated and resulted in dramatic and durable responses. The combination of temozolomide with other chemotherapeutic agents represents a promising strategy for treating patients with lung cancer and recurrent brain metastases and merits further study.
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PMID:Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer. 1260 33

Temozolomide (TMZ) has shown modest efficacy in the treatment of recurrent brain metastasis (BM). We designed a new regimen utilizing dose-intensified, protracted course of TMZ in combination with vinorelbine, a lipophilic large-spectrum agent, in an attempt to improve the efficacy of TMZ. This phase I study was conducted to establish the maximum tolerated dose (MTD) of vinorelbine for this combination. Patients with recurrent or progressive BM were eligible. Chemotherapy consisted of 28-day cycles with TMZ (150 mg/m2, days 1-7 and 15-21) and vinorelbine (days one and eight at escalating doses). The starting dose was 15 mg/m2, with increments of 5 mg/m2 for each cohort of 3-6 patients, until MTD was reached (30 mg/m2). A total of 21 patients were enrolled; the median age was 59 (41-77). The primary tumor was lung cancer in 13 patients (NSCLC in 10, SCLC in 3), breast in 6, renal in 1 and endometrial in 1. Vinorelbine dose was 15 mg/m2 in seven patients, 20 mg/m2 in five, 25 mg/m2 in four and 30 mg/m2 in six. Grades 3 and 4 neutropenia developed in six patients, lymphopenia in nine, and thrombocytopenia in six; other toxicities were rare. No dose-limiting toxicity was seen. Out of 18 evaluable patients 2 had a radiographic response (one partial and one minor). Disease was stable in 6 of 18 patients and the median survival was 27 weeks. This regimen was well tolerated and a phase II trial using a dose of 30 mg/m2 of vinorelbine is warranted.
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PMID:Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: a phase I trial. 1661 43

This phase I study was carried out to evaluate the optimal dose of temozolomide in combination with carboplatin and paclitaxel in patients with advanced solid tumors. Patients with advanced melanoma or small cell lung cancer that could benefit from the combination of carboplatin and paclitaxel were eligible. A standard 3+3 patient cohort dose escalation design was used. Paclitaxel and carboplatin were administered at fixed doses of 175 mg/m on day 1 and an area under the curve of 5, respectively. Temozolomide was administered at a dose of 75 mg/m/day from days 2-6 and subsequent cohorts were dose escalated by 25 mg/m increments. Cycles were repeated every 28 days. The primary objective of this study was to determine the maximum tolerated dose of this combination. Fourteen patients were enrolled and 12 patients were evaluable for toxicity and response (six with melanoma and six with small cell lung cancer). The maximum tolerated dose of temozolomide was 125 mg/m, with fixed doses of carboplatin and paclitaxel. There were no treatment delays nor dose reductions at this level. There were two partial responses and two patients with stable disease in the melanoma group. Four patients had a partial response, and one had stable disease in the small cell lung cancer group. There were sustained responses in three of the four patients with melanoma who achieved a clinical benefit. In conclusion, the combination of carboplatin, paclitaxel, and temozolomide is well tolerated and warrants further study.
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PMID:Phase I dose finding study of carboplatin, paclitaxel, and temozolomide in advanced solid tumors. 2116 71

Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O6-methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. In order to identify the status of MGMT promoter methylation and IDH1/2 mutation of SCLC in China, 33 SCLC specimens from patients that underwent surgery were retrospectively collected in Zhejiang Cancer Hospital (Hangzhou, China) between 2008 and 2014. High-resolution melting analysis and methylation-specific polymerase chain reaction were used to detect MGMT promoter methylation, and polymerase chain reaction amplification and Sanger sequencing were utilized to detect IDH1/2 mutation. Of the 33 examined SCLC specimens, MGMT promoter methylation was detected in 17 patients (51.5%), and no IDH1/2 mutations were detected in the analyzed samples. These findings indicate that the IDH1/2 mutation may not be an ideal marker in SCLC patients treated with temozolomide. Future studies on the predictive and prognostic value of MGMT promoter methylation are urgently required for patients with relapsed SCLC treated with temozolomide in China.
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PMID:O6-methyl-guanine-DNA methyltransferase methylation and IDH1/2 mutation in small cell lung cancer. 2867 45