Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient was a 66-year-old man who had undergone right upper lobectomy and ND 2a systematic lymph node dissection for lung cancer (M/D adenocarcinoma, p-stage IB) in March of 1999 . On November 2003, postoperative routine chest computed tomography(CT) demonstrated a mass in left S6, and pathological diagnosis revealed P/D squamous cell carcinoma (cT1N2M0, stage IIIA) by CT-guided needle biopsy and mediastinoscopy. At first, we tried two courses of a combination chemotherapy consisting of carboplatin (CBDCA) and paclitaxel every 3 weeks. After 2 courses, the regimen was stopped because of grade 3 arthritis. Then, two courses of CBDCA and gemcitabine were performed. The evaluation of the response was SD by the guidelines of Response Evaluation Criteria in Solid Tumor Groups. Next, gefitinib was orally administered for 6 months but the tumor and mediastinal lymph nodes were growing. In January 2005, oral administration of TS-1 (60 mg/1, 2 courses, 75 mg/3-6 courses) was begun twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. The response was PR (the tumor decreased by 46%), no serious adverse effect was observed, and the patient maintained good quality of life throughout the chemotherapy. This case suggests that TS-1+CDDP chemotherapy may be an effective treatment in patients with advanced lung cancer even after many protocols of chemotherapy.
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PMID:[A case of a second cancer of metachronous multiple primary non-small cell lung cancer successfully treated with TS-1 and CDDP chemotherapy]. 1668 65

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are critical enzymes in nucleic acid metabolism. Proliferating cell nuclear antigen (PCNA) is a specific protein that is correlated with proliferative activity of cells. The TS gene has a variable number of tandem repeats (VNTR) in its 5'-untranslated region and a single nucleotide polymorphism (SNP) in the VNTR area. We examined the association of in vitro sensitivity to anticancer drugs with TS polymorphism, TS, DPD, and PCNA mRNA expression using human lung cancer tissues. Seventy-eight surgically resected lung cancer tissues were tested for in vitro sensitivity to 5-fluorouracil, cisplatin (CDDP), carboplatin (CBDCA), irinotecan, docetaxel, and gemcitabine by histoculture and MTT assay. The TS polymorphisms were analyzed by PCR and PCR-RFLP. TS, DPD, and PCNA mRNA expression levels were quantified by real-time RT-PCR and normalized relative to beta-actin mRNA expression. The inhibition rates (IRs) of CDDP and CBDCA were significantly correlated with TS/PCNA, the ratio of TS/actin and PCNA/actin, and DPD/PCNA, the ratio of DPD/actin and PCNA/actin. This correlation was further explored by subgroup analyses according to TS VNTR or TS functional type, in which 2R/3G, 3C/3G, or 3G/3G were classified into H-type group and 2R/2R, 2R/3C, or 3C/3C into L-type group. The associations of TS/PCNA and DPD/PCNA with the IRs of CDDP, CBDCA remained significant in the 3R/3R group and H-type group. These results suggest that in vitro sensitivity to platinum-derived drugs, CDDP and CBDCA, is associated with PCNA-normalized mRNA expression of TS and DPD in human lung cancer tissues, as affected by the TS polymorphism. The clinical significance of these pharmacogenomic markers for chemotherapy regimens with platinum-derived drugs should be investigated further for personalized treatment of lung cancer.
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PMID:In vitro sensitivity to platinum-derived drugs is associated with expression of thymidylate synthase and dihydropyrimidine dehydrogenase in human lung cancer. 1668 92

A gene-drug correlation analysis was previously performed in lung cancer cell lines using the NC160 program. On the basis of this work, a phase I/II pilot study of weekly paclitaxel and carboplatin (CBDCA) was subsequently planned for refractory or recurrent non-small cell lung cancer (NSCLC). Safety and antitumor effects were evaluable in all 30 patients registered for this study. Seven patients were stage IIIB and 23 were stage IV. At level 5 (paclitaxel 100 mg/m2 and CBDCA AUCS), toxicities were not dose-limiting factors, but three out of the initial six cases had infusion skips. Our recommended dose was paclitaxel 100 mg/m2 and CBDCA AUC5. The response rate was 50% (9/18)(95% CI: 27-73%) in step 5. The median survival time was 12 months. This combination showed a promising clinical activity with mild toxicity and should be selected for the investigational arm of phase III trials to be compared with either docetaxel or pemetrexed.
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PMID:Phase I/II study of paclitaxel + carboplatin for refractory or recurrent non-small cell lung cancer. 1688 38

Lung cancer is one of the most common solid tumors to develop metastases to bone. The prognosis of patients with metastatic lung cancer to bones is short,usually less than 6 months. The treatment requires a multidisciplinary approach that addresses radiotherapy, surgery, chemotherapy, and medical therapy with analgesics and bisphosphonates. Radiotherapy for metastatic bone tumor is a mainstay to relieve pain and control the localized disease. Doses in the range of 20 Gy in 5 fractions, 30 Gy in 10 fractions are acceptable in most circumstances. Prophylactic fixation for long bone fractures is recommended in cases where 30 to 50% of the cortex has been destroyed, pain is present after radiotherapy, or life expectancy is more than 3 months. Systemic chemotherapy has been proved to prolong survival of patients with metastatic non-small-cell lung cancer (NSCLC) as well as extensive small cell lung cancer (SCLC). Combination chemotherapy of platinum and a new drug is recommended in NSCLC patients with good performance status (PS). Gefitinib in upfront or second-line treatment is an optional therapy in adenocarcinoma patients without a history of smoking. Cisplatin combined with etoposide or irinotecan is a standard therapy in SCLC patients with PS 0 or 1. Carboplatin and etoposide is a treatment of choice in SCLC patients with PS 2 or 3. Medical management of cancer pain requires nonsteroidal anti-inflammatory drugs and opioids. Cancer pain that necessitates more than 120 mg of oral morphine is morphine-resistant pain and requires some adjuvant drugs such as corticosteroids, ketamine,anticonvulsants, or local anesthetics. The third generation bisphosphonate zoledronate has been demonstrated to improve cancer pain and to prevent skeletal morbidity in lung cancer patients with metastatic bone disease.
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PMID:[Lung cancer with bone metastasis]. 1691 19

The inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II associated with increased in vitro sensitivity of tumors to etoposide. Maximal synergy has been observed for the sequence of topotecan followed by etoposide. Carboplatin has clinical activity when combined with either of these two agents. These interactions were the pharmacologic rationale for topotecan p.o. days 1-5, carboplatin i.v. day 6, and etoposide p.o. days 6-10. Three successive dose levels were explored: (1) topotecan 2mg/day, carboplatin AUC 5, etoposide 150 mg/day; (2) topotecan 3mg/day, carboplatin AUC 5, etoposide 150 mg/day; and (3) topotecan 3mg/day, carboplatin AUC 5, etoposide 200mg/day. Filgrastim 5 microg/kg/day was injected s.c. days 11-18. Up to 6 cycles were administered every 21 days. Eligible patients had measurable or evaluable, extensive disease, small lung cell lung cancer, no prior chemotherapy, ECOG performance status 0-2, and adequate hematologic, renal, and hepatic function. Follow-up was weekly for CBC. Tumor response was assessed after 2 and 6 cycles. Dose limiting toxicity (DLT) was defined as any of the following in cycle 1: grade 3 or 4 non-hematologic toxicity other than nausea and vomiting, grade 4 neutropenia lasting more than 3 days, neutropenic fever or sepsis, grade 4 thrombocytopenia, or failure to recover neutrophils >or=1500/microl or platelets >or=100,000/microl by day 28. Ten patients were enrolled: median age 62 (range, 50-79); female/male 4/6; and performance status 0/1/2 in 2/7/1. Three patients each were treated on dose levels 1 and 2 without DLT. The first 2 patients entered on dose level 3 had no DLT. The third patient on dose level 3 developed grade 4 neutropenia lasting more than 3 days, neutropenic fever, and grade 4 thrombocytopenia on day 15 of cycle 1. The fourth patient on dose level 3 developed grade 4 thrombocytopenia on day 18 of cycle 1. One patient received only 1 cycle and was not evaluable for response. Seven patients completed 6 cycles: 1 had a complete response and 6 achieved a partial response. The third patient on dose level 3 received 2 cycles and had stable disease, but had to be removed from protocol treatment because of grade 4 neutropenia despite dose reduction in cycle 2. The fourth patient on dose level 3 achieved a partial response, but had to be removed from protocol therapy after cycle 5 because of recurrent grade 4 thrombocytopenia. In conclusion, neutropenia and thrombocytopenia were dose-limiting. The maximum tolerated dose (MTD) is topotecan 3mg/day p.o. days 1-5, carboplatin AUC 5i.v. day 6, and etoposide 150 mg/day p.o. days 6-10 with filgrastim.
Lung Cancer 2006 Dec
PMID:Phase I and pharmacologic study of sequential topotecan-carboplatin-etoposide in patients with extensive stage small cell lung cancer. 1704 3

Recently, adjuvant chemoradiotherapy showed possible survival advantage in the western prospective studies. A feasibility study was conducted. Adjuvant concurrent chemoradiotherapy with carboplatin (CBDCA) + paclitaxel (PTX) was performed to 4 outpatients with resected locally advanced lung cancer. A total of 60 Gy was given during about 7 weeks, and concurrent CBDCA 2 mg/AUC + PTX 45 mg/m2 was administered weekly. Grade 2 neutropenia was seen in 2 patients, grade 2 esophagitis was seen in 1, and grade 2 peripheral neuritis was in 1. Grade 3 or more toxicity was never seen. One patient had to be hospitalized because of esophagitis, but other 3 patients had completed all course of the therapy as outpatients. Adjuvant concurrent chemoradiotherapy with CBDCA + PTX was thought to be feasible to the resected locally advanced lung cancer patients. Prospective study will be conducted to examine the efficacy of this treatment.
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PMID:[Adjuvant concurrent chemoradiotherapy for resected locally advanced lung cancer outpatients]. 1818 67

In this study we analyze the usefulness of the histoculture drug response assay (HDRA) based perioperative chemotherapy for non-small cell lung cancer. From 2001 to 2006, we examined the chemosensitivity of 70 lung cancer tissues to cisplatin (CDDP), carboplatin (CBDCA), paclitaxel, docetaxel, gemcitabine and irinotecan. In 16 patients with stage III lung cancer who treated induction therapy, the response rate was 100% of 5 patients treated chemotherapy using 2 HDRA-positive drugs, 50% of 8 patient treeated using 1 positive drugs and 0% of 3 patients treated using negative drugs, respectively. The 3-year survival rate of the 5 patients treated using 2 positive drugs was better than that of 11 patient treated using 1 or non positive drugs (p = 0.07). In 39 patients with stage III lung cancer who treated adjuvant chemotherapy, the survival rate of the 14 patients treated chemotherapy using 2 positive drugs was significantly better than that of 25 patients treated using 1 or non positive drugs (p = 0.03). Therefore, HDRA may useful to the improvement of the response to chemotherapy and survival.
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PMID:[The effect of the histoculture drug response assay (HDRA) based perioperative chemotherapy for non-small cell lung cancer]. 1818 69

The patient was a 63-year-old man who consulted our hospital with complaints of a cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right S1 hilar area with spiculation, disseminated nodule in right lung, and pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and chemotherapy was initiated. The chemotherapy was given in the order of CBDCA (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2 weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a breast CT detected tumor size reduction following completion of the first course. However, after completion of three courses, the breast CT found tumor-enlargement again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the treatment was discontinued due to skin rash. We once experienced a size reduction with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7, 14) combination chemotherapy was conducted at 4-week intervals. After two courses were completed, tumor size reduction was observed by breast XP and CT. The response rate was 40.0%. Currently, seven courses were completed, and we will continue this treatment due to the tumor response of SD. The S-1 single treatment and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case of NSCLC with refractoriness to multiple cancer drug chemotherapy. This combination treatment should be investigated further for its therapeutic benefit.
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PMID:[A case of multidrug-resistant squamous cell lung carcinoma responding to S-1 plus CPT-11 combination chemotherapy]. 1834 99

Nowadays cisplatin doublets are considered the gold-standard treatment in advanced non-small cell lung cancer (NSCLC) patients, but are often associated to poor toxicity profile. In the last years different schedules have been developed in order to improve the tolerability of these regimens. Carboplatin is gradually replacing cisplatin in clinical practice as well as in clinical trials even if it is still unclear whether it has an equivalent efficacy compared to cisplatin. Oxaliplatin, the trans-l oxalato platinum compound, showed encouraging antineoplastic activity and favourable toxicity profile in NSCLC, but confirmatory randomized phase III trials are warranted. We performed a literature search in order to better understand the possible role of oxaliplatin-based combinations in advanced NSCLC treatment strategies.
Lung Cancer 2008 Jun
PMID:Oxaliplatin doublets in non-small cell lung cancer: a literature review. 1844 88

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non-small-cell lung cancer (NSCLC). Docetaxel is the only agent currently approved for both first- and second-line treatment of advanced NSCLC. Multiple randomized clinical trials have established the efficacy of platinum-docetaxel regimens for the first-line treatment of advanced NSCLC. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II trials. This review article summarizes recent studies of docetaxel as a single agent and in combination regimens with cytotoxic or targeted therapies in the management of patients with advanced NSCLC.
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PMID:Docetaxel in the treatment of advanced non-small-cell lung cancer. 1869 60


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